Targeting the Virus Capsid as a Tool to Fight RNA Viruses
Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
35215767
PubMed Central
PMC8879806
DOI
10.3390/v14020174
PII: v14020174
Knihovny.cz E-zdroje
- Klíčová slova
- antiviral compounds, antivirals, assembly inhibitor, capsid assembly, capsid binding, capsid targeting, virus inhibitor,
- MeSH
- antivirové látky chemie farmakologie MeSH
- infekce RNA viry farmakoterapie virologie MeSH
- lidé MeSH
- replikace viru účinky léků MeSH
- RNA-viry účinky léků fyziologie MeSH
- sestavení viru účinky léků MeSH
- virové plášťové proteiny antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antivirové látky MeSH
- virové plášťové proteiny MeSH
Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of efficient vaccines, to target the virus by developed antibodies, others focus on finding antiviral compounds with activities that inhibit selected virus replication steps. Currently, there is an increasing number of antiviral drugs on the market; however, some have unpleasant side effects, are toxic to cells, or the viruses quickly develop resistance to them. As the current situation shows, the combination of multiple antiviral strategies or the combination of the use of various compounds within one strategy is very important. The most desirable are combinations of drugs that inhibit different steps in the virus life cycle. This is an important issue especially for RNA viruses, which replicate their genomes using error-prone RNA polymerases and rapidly develop mutants resistant to applied antiviral compounds. Here, we focus on compounds targeting viral structural capsid proteins, thereby inhibiting virus assembly or disassembly, virus binding to cellular receptors, or acting by inhibiting other virus replication mechanisms. This review is an update of existing papers on a similar topic, by focusing on the most recent advances in the rapidly evolving research of compounds targeting capsid proteins of RNA viruses.
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Drake J.W., Holland J.J. Mutation rates among RNA viruses. Proc. Natl. Acad. Sci. USA. 1999;96:13910–13913. doi: 10.1073/pnas.96.24.13910. PubMed DOI PMC
Castro C., Arnold J.J., Cameron C.E. Incorporation fidelity of the viral RNA-dependent RNA polymerase: A kinetic, thermodynamic and structural perspective. Virus Res. 2005;107:141–149. doi: 10.1016/j.virusres.2004.11.004. PubMed DOI PMC
An W.F., Tolliday N. Cell-based assays for high-throughput screening. Mol. Biotechnol. 2010;45:180–186. doi: 10.1007/s12033-010-9251-z. PubMed DOI
Rumlová M., Ruml T. In vitro methods for testing antiviral drugs. Biotechnol. Adv. 2018;36:557–576. doi: 10.1016/j.biotechadv.2017.12.016. PubMed DOI PMC
Bleicher K.H., Böhm H.J., Müller K., Alanine A.I. Hit and lead generation: Beyond high-throughput screening. Nat. Rev. Drug Discov. 2003;2:369–378. doi: 10.1038/nrd1086. PubMed DOI
Lenz G.R., Nash H.M., Jindal S. Chemical ligands, genomics and drug discovery. Drug Discov. Today. 2000;5:145–156. doi: 10.1016/S1359-6446(00)01468-9. PubMed DOI
Bharat T.A., Davey N.E., Ulbrich P., Riches J.D., de Marco A., Rumlova M., Sachse C., Ruml T., Briggs J.A. Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy. Nature. 2012;487:385–389. doi: 10.1038/nature11169. PubMed DOI
Schur F.K., Hagen W.J., Rumlova M., Ruml T., Muller B., Krausslich H.G., Briggs J.A. Structure of the immature HIV-1 capsid in intact virus particles at 8.8 A resolution. Nature. 2015;517:505–508. doi: 10.1038/nature13838. PubMed DOI
Freed E.O. HIV-1 assembly, release and maturation. Nat. Rev. Microbiol. 2015;13:484–496. doi: 10.1038/nrmicro3490. PubMed DOI PMC
Hadravová R., Rumlová M., Ruml T. FAITH—Fast assembly inhibitor test for HIV. Virology. 2015;486:78–87. doi: 10.1016/j.virol.2015.08.029. PubMed DOI
Dostálková A., Hadravová R., Kaufman F., Křížová I., Škach K., Flegel M., Hrabal R., Ruml T., Rumlová M. A simple, high-throughput stabilization assay to test HIV-1 uncoating inhibitors. Sci. Rep. 2019;9:17076. doi: 10.1038/s41598-019-53483-w. PubMed DOI PMC
Zhang X., Jia R., Zhou J., Wang M., Yin Z., Cheng A. Capsid-targeted viral inactivation: A novel tactic for inhibiting replication in viral infections. Viruses. 2016;8:258. doi: 10.3390/v8090258. PubMed DOI PMC
Natsoulis G., Seshaiah P., Federspiel M.J., Rein A., Hughes S.H., Boeke J.D. Targeting of a nuclease to murine leukemia virus capsids inhibits viral multiplication. Proc. Natl. Acad. Sci. USA. 1995;92:364–368. doi: 10.1073/pnas.92.2.364. PubMed DOI PMC
Beterams G., Nassal M. Significant interference with Hepatitis B virus replication by a Core-nuclease fusion protein. J. Biol. Chem. 2001;276:8875–8883. doi: 10.1074/jbc.M006335200. PubMed DOI
Qin C.F., Qin E.D. Capsid-targeted viral inactivation can destroy dengue 2 virus from within in vitro. Arch. Virol. 2006;151:379–385. doi: 10.1007/s00705-005-0631-9. PubMed DOI
Okui N., Sakuma R., Kobayashi N., Yoshikura H., Kitamura T., Chiba J., Kitamura Y. Packageable antiviral therapeutics against human immunodeficiency virus type 1: Virion-targeted virus inactivation by incorporation of a single-chain antibody against viral integrase into progeny virions. Hum. Gene Ther. 2000;11:537–546. doi: 10.1089/10430340050015725. PubMed DOI
Kobinger G.P., Borsetti A., Nie Z., Mercier J., Daniel N., Göttlinger H.G., Cohen A. Virion-targeted viral inactivation of human immunodeficiency virus type 1 by using Vpr fusion proteins. J. Virol. 1998;72:5441–5448. doi: 10.1128/JVI.72.7.5441-5448.1998. PubMed DOI PMC
Schumann G., Qin L., Rein A., Natsoulis G., Boeke J.D. Therapeutic effect of Gag-nuclease fusion protein on retrovirus-infected cell cultures. J. Virol. 1996;70:4329–4337. doi: 10.1128/jvi.70.7.4329-4337.1996. PubMed DOI PMC
Natsoulis G., Boeke J.D. New antiviral strategy using capsid-nuclease fusion proteins. Nature. 1991;352:632–635. doi: 10.1038/352632a0. PubMed DOI
Schumann G., Cannon K., Ma W.P., Crouch R.J., Boeke J.D. Antiretroviral effect of a gag-RNase HI fusion gene. Gene Ther. 1997;4:593–599. doi: 10.1038/sj.gt.3300421. PubMed DOI
Loukachevitch L.V., Egli M. Crystallization and preliminary X-ray analysis of Escherichia coli RNase HI-dsRNA complexes. Pt 2Acta Crystallogr. Sect. F Struct Biol. Cryst. Commun. 2007;63:84–88. doi: 10.1107/S1744309106055461. PubMed DOI PMC
VanBrocklin M., Ferris A.L., Hughes S.H., Federspiel M.J. Expression of a murine leukemia virus Gag-Escherichia coli RNase HI fusion polyprotein significantly inhibits virus spread. J. Virol. 1997;71:3312–3318. doi: 10.1128/jvi.71.4.3312-3318.1997. PubMed DOI PMC
Ryoo J., Choi J., Oh C., Kim S., Seo M., Kim S.Y., Seo D., Kim J., White T.E., Brandariz-Nuñez A., et al. The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. Nat. Med. 2014;20:936–941. doi: 10.1038/nm.3626. PubMed DOI PMC
Abbott T.R., Dhamdhere G., Liu Y., Lin X., Goudy L., Zeng L., Chemparathy A., Chmura S., Heaton N.S., Debs R., et al. Development of CRISPR as an antiviral strategy to combat SARS-CoV-2 and Influenza. Cell. 2020;181:865–876.e12. doi: 10.1016/j.cell.2020.04.020. PubMed DOI PMC
Zhao Y., Li Y., Liu J., Liu Z., Huang Y., Lei J., Li S., Xue C. Adenoviral-vector mediated transfer of HBV-targeted ribonuclease can inhibit HBV replication in vivo. Biochem. Biophys. Res. Commun. 2008;371:541–545. doi: 10.1016/j.bbrc.2008.04.121. PubMed DOI
Qin B., Cheng L., Chen J., Jiang X., Zou S. Construction of transgenic P0 grass carp by capsid-targeted viral inactivation of reovirus. J. Fisher China. 2014;38:1956–1963.
Nangola S., Urvoas A., Valerio-Lepiniec M., Khamaikawin W., Sakkhachornphop S., Hong S.S., Boulanger P., Minard P., Tayapiwatana C. Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein. Retrovirology. 2012;9:17. doi: 10.1186/1742-4690-9-17. PubMed DOI PMC
Praditwongwan W., Chuankhayan P., Saoin S., Wisitponchai T., Lee V.S., Nangola S., Hong S.S., Minard P., Boulanger P., Chen C.-J., et al. Crystal structure of an antiviral ankyrin targeting the HIV-1 capsid and molecular modeling of the ankyrin-capsid complex. J. Comput. Aided Mol. Des. 2014;28:869–884. doi: 10.1007/s10822-014-9772-9. PubMed DOI
Sticht J., Humbert M., Findlow S., Bodem J., Müller B., Dietrich U., Werner J., Kräusslich H.G. A peptide inhibitor of HIV-1 assembly in vitro. Nat. Struct. Mol. Biol. 2005;12:671–677. doi: 10.1038/nsmb964. PubMed DOI
Ternois F., Sticht J., Duquerroy S., Kräusslich H.G., Rey F.A. The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor. Nat. Struct. Mol. Biol. 2005;12:678–682. doi: 10.1038/nsmb967. PubMed DOI
Kozisek M., Durcak J., Konvalinka J. Thermodynamic characterization of the peptide assembly inhibitor binding to HIV-1 capsid protein. Retrovirology. 2013;10:P108. doi: 10.1186/1742-4690-10-S1-P108. DOI
Zhang H., Zhao Q., Bhattacharya S., Waheed A.A., Tong X., Hong A., Heck S., Curreli F., Goger M., Cowburn D., et al. A cell-penetrating helical peptide as a potential HIV-1 inhibitor. J. Mol. Biol. 2008;378:565–580. doi: 10.1016/j.jmb.2008.02.066. PubMed DOI PMC
Bhattacharya S., Zhang H., Debnath A.K., Cowburn D. Solution structure of a hydrocarbon stapled peptide inhibitor in complex with monomeric C-terminal domain of HIV-1 capsid. J. Biol. Chem. 2008;283:16274–16278. doi: 10.1074/jbc.C800048200. PubMed DOI PMC
Zhang H., Curreli F., Waheed A.A., Mercredi P.Y., Mehta M., Bhargava P., Scacalossi D., Tong X., Lee S., Cooper A., et al. Dual-acting stapled peptides target both HIV-1 entry and assembly. Retrovirology. 2013;10:136. doi: 10.1186/1742-4690-10-136. PubMed DOI PMC
Garzón M.T., Lidón-Moya M.C., Barrera F.N., Prieto A., Gómez J., Mateu M.G., Neira J.L. The dimerization domain of the HIV-1 capsid protein binds a capsid protein-derived peptide: A biophysical characterization. Protein Sci. 2004;13:1512–1523. doi: 10.1110/ps.03555304. PubMed DOI PMC
Bocanegra R., Nevot M., Doménech R., López I., Abián O., Rodríguez-Huete A., Cavasotto C.N., Velázquez-Campoy A., Gómez J., Martínez M., et al. Rationally designed interfacial peptides are efficient in vitro inhibitors of HIV-1 capsid assembly with antiviral activity. PLoS ONE. 2011;6:e23877. doi: 10.1371/journal.pone.0023877. PubMed DOI PMC
Pornillos O., Ganser-Pornillos B.K., Kelly B.N., Hua Y., Whitby F.G., Stout C.D., Sundquist W.I., Hill C.P., Yeager M. X-ray structures of the hexameric building block of the HIV capsid. Cell. 2009;137:1282–1292. doi: 10.1016/j.cell.2009.04.063. PubMed DOI PMC
Zhang H., Curreli F., Zhang X., Bhattacharya S., Waheed A.A., Cooper A., Cowburn D., Freed E.O., Debnath A.K. Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain. Retrovirology. 2011;8:28. doi: 10.1186/1742-4690-8-28. PubMed DOI PMC
Tang C., Loeliger E., Kinde I., Kyere S., Mayo K., Barklis E., Sun Y., Huang M., Summers M.F. Antiviral inhibition of the HIV-1 capsid protein. J. Mol. Biol. 2003;327:1013–1020. doi: 10.1016/S0022-2836(03)00289-4. PubMed DOI
Kelly B.N., Kyere S., Kinde I., Tang C., Howard B.R., Robinson H., Sundquist W.I., Summers M.F., Hill C.P. Structure of the antiviral assembly inhibitor CAP-1 complex with the HIV-1 CA protein. J. Mol. Biol. 2007;373:355–366. doi: 10.1016/j.jmb.2007.07.070. PubMed DOI PMC
Prevelige P. Small molecule inhibitors of HIV-1 capsid assembly. Application No. 12/090,361. U.S. Patent. 2009 July 9;
Tian B., He M., Tang S., Hewlett I., Tan Z., Li J., Jin Y., Yang M. Synthesis and antiviral activities of novel acylhydrazone derivatives targeting HIV-1 capsid protein. Bioorg. Med. Chem. Lett. 2009;19:2162–2167. doi: 10.1016/j.bmcl.2009.02.116. PubMed DOI
Shi J., Zhou J., Shah V.B., Aiken C., Whitby K. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization. J. Virol. 2011;85:542–549. doi: 10.1128/JVI.01406-10. PubMed DOI PMC
Sundquist W.I., Hill C.P. How to assemble a capsid. Cell. 2007;131:17–19. doi: 10.1016/j.cell.2007.09.028. PubMed DOI
Lemke C.T., Titolo S., von Schwedler U., Goudreau N., Mercier J.F., Wardrop E., Faucher A.M., Coulombe R., Banik S.S., Fader L., et al. Distinct effects of two HIV-1 capsid assembly inhibitor families that bind the same site within the N-terminal domain of the viral CA protein. J. Virol. 2012;86:6643–6655. doi: 10.1128/JVI.00493-12. PubMed DOI PMC
Fader L.D., Bethell R., Bonneau P., Bös M., Bousquet Y., Cordingley M.G., Coulombe R., Deroy P., Faucher A.M., Gagnon A., et al. Discovery of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly. Bioorg. Med. Chem. Lett. 2011;21:398–404. doi: 10.1016/j.bmcl.2010.10.131. PubMed DOI
Goudreau N., Lemke C.T., Faucher A.M., Grand-Maître C., Goulet S., Lacoste J.E., Rancourt J., Malenfant E., Mercier J.F., Titolo S., et al. Novel inhibitor binding site discovery on HIV-1 capsid N-terminal domain by NMR and X-ray crystallography. ACS Chem. Biol. 2013;8:1074–1082. doi: 10.1021/cb400075f. PubMed DOI
Urano E., Kuramochi N., Ichikawa R., Murayama S.Y., Miyauchi K., Tomoda H., Takebe Y., Nermut M., Komano J., Morikawa Y. Novel postentry inhibitor of human immunodeficiency virus type 1 replication screened by yeast membrane-associated two-hybrid system. Antimicrob. Agents Chemother. 2011;55:4251–4260. doi: 10.1128/AAC.00299-11. PubMed DOI PMC
Kamo M., Tateishi H., Koga R., Okamoto Y., Otsuka M., Fujita M. Synthesis of the biotinylated anti-HIV compound BMMP and the target identification study. Bioorg. Med. Chem. Lett. 2016;26:43–45. doi: 10.1016/j.bmcl.2015.11.036. PubMed DOI
Blair W.S., Pickford C., Irving S.L., Brown D.G., Anderson M., Bazin R., Cao J., Ciaramella G., Isaacson J., Jackson L., et al. HIV capsid is a tractable target for small molecule therapeutic intervention. PLoS Pathog. 2010;6:e1001220. doi: 10.1371/journal.ppat.1001220. PubMed DOI PMC
Fricke T., Brandariz-Nuñez A., Wang X., Smith A.B., 3rd, Diaz-Griffero F. Human cytosolic extracts stabilize the HIV-1 core. J Virol. 2013;87:10587–10597. doi: 10.1128/JVI.01705-13. PubMed DOI PMC
Bhattacharya A., Alam S.L., Fricke T., Zadrozny K., Sedzicki J., Taylor A.B., Demeler B., Pornillos O., Ganser-Pornillos B.K., Diaz-Griffero F., et al. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Proc. Natl. Acad. Sci. USA. 2014;111:18625–18630. doi: 10.1073/pnas.1419945112. PubMed DOI PMC
Saito A., Ferhadian D., Sowd G.A., Serrao E., Shi J., Halambage U.D., Teng S., Soto J., Siddiqui M.A., Engelman A.N., et al. Roles of capsid-interacting host factors in multimodal inhibition of HIV-1 by PF74. J. Virol. 2016;90:5808–5823. doi: 10.1128/JVI.03116-15. PubMed DOI PMC
Yant S.R., Mulato A., Hansen D., Tse W.C., Niedziela-Majka A., Zhang J.R., Stepan G.J., Jin D., Wong M.H., Perreira J.M., et al. A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model. Nat. Med. 2019;25:1377–1384. doi: 10.1038/s41591-019-0560-x. PubMed DOI PMC
Singh K., Gallazzi F., Hill K.J., Burke D.H., Lange M.J., Quinn T.P., Neogi U., Sönnerborg A. GS-CA compounds: First-in-class HIV-1 capsid inhibitors covering multiple grounds. Front. Microbiol. 2019;10:1227. doi: 10.3389/fmicb.2019.01227. PubMed DOI PMC
Ehrlich L.S., Agresta B.E., Carter C.A. Assembly of recombinant human immunodeficiency virus type 1 capsid protein in vitro. J. Virol. 1992;66:4874–4883. doi: 10.1128/jvi.66.8.4874-4883.1992. PubMed DOI PMC
Ganser-Pornillos B.K., von Schwedler U.K., Stray K.M., Aiken C., Sundquist W.I. Assembly properties of the human immunodeficiency virus type 1 CA protein. J. Virol. 2004;78:2545–2552. doi: 10.1128/JVI.78.5.2545-2552.2004. PubMed DOI PMC
Tse W.C., Link J.O., Mulato A., Niedziela-Majka A., Rowe W., Somoza J.R., Villasenor A.G., Yant S.R., Zhang J.R., Zheng J. Discovery of Novel Potent HIV Capsid Inhibitors with Long-Acting Potential; Proceedings of the CROI; Seattle, WA, USA. 13–16 February 2017.
Zheng J., Yant S.R., Ahmadyar S., Chan T.Y., Chiu A., Cihlar T., Link J.O., Lu B., Mwangi J., Rowe W., et al. Open Forum Infectious Diseases. Volume 5. Oxford University Press; Oxford, UK: 2018. 539. GS-CA2: A novel, potent, and selective first-in-class inhibitor of HIV-1 capsid function displays nonclinical pharmacokinetics supporting long-acting potential in humans; pp. S199–S200.
Jennifer E., Sager R.B., Martin R., Steve K.W., John L., Scott D.S., Winston C.T., Anita M. Safety and PK of subcutaneous GS-6207, a novel HIV-1 capsid inhibitor; Proceedings of the CROI; Seattle, WA, USA. 4–7 March 2019.
Daar E.S., McDonald C., Crofoot G., Ruane P., Sinclair G., Patel H., Begley R., Liu Y.P., Brainard D.M., Hyland R.H., et al. Single doses of long-acting capsid inhibitor GS-6207 administered by subcutaneous injection are safe and efficacious in people living with HIV; Proceedings of the 17th European AIDS Conference; Basel, Switzerland. 6–9 November 2019.
Link J.O., Rhee M.S., Tse W.C., Zheng J., Somoza J.R., Rowe W., Begley R., Chiu A., Mulato A., Hansen D., et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020;584:614–618. doi: 10.1038/s41586-020-2443-1. PubMed DOI PMC
Zila V., Margiotta E., Turoňová B., Müller T.G., Zimmerli C.E., Mattei S., Allegretti M., Börner K., Rada J., Müller B., et al. Cone-shaped HIV-1 capsids are transported through intact nuclear pores. Cell. 2021;184:1032–1046.e18. doi: 10.1016/j.cell.2021.01.025. PubMed DOI PMC
Lamorte L., Titolo S., Lemke C.T., Goudreau N., Mercier J.F., Wardrop E., Shah V.B., von Schwedler U.K., Langelier C., Banik S.S., et al. Discovery of novel small-molecule HIV-1 replication inhibitors that stabilize capsid complexes. Antimicrob. Agents Chemother. 2013;57:4622–4631. doi: 10.1128/AAC.00985-13. PubMed DOI PMC
Fricke T., Buffone C., Opp S., Valle-Casuso J., Diaz-Griffero F. BI-2 destabilizes HIV-1 cores during infection and prevents binding of CPSF6 to the HIV-1 capsid. Retrovirology. 2014;11:120. doi: 10.1186/s12977-014-0120-x. PubMed DOI PMC
Ganser B.K., Li S., Klishko V.Y., Finch J.T., Sundquist W.I. Assembly and analysis of conical models for the HIV-1 core. Science. 1999;283:80–83. doi: 10.1126/science.283.5398.80. PubMed DOI
Briggs J.A., Kräusslich H.G. The molecular architecture of HIV. J. Mol. Biol. 2011;410:491–500. doi: 10.1016/j.jmb.2011.04.021. PubMed DOI
Price A.J., Fletcher A.J., Schaller T., Elliott T., Lee K., KewalRamani V.N., Chin J.W., Towers G.J., James L.C. CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. PLoS Pathog. 2012;8:e1002896. doi: 10.1371/journal.ppat.1002896. PubMed DOI PMC
Sun L., Dick A., Meuser M.E., Huang T., Zalloum W.A., Chen C.-H., Cherukupalli S., Xu S., Ding X., Gao P., et al. Design, synthesis, and mechanism study of benzenesulfonamide-containing phenylalanine derivatives as novel HIV-1 capsid inhibitors with improved antiviral activities. J. Med. Chem. 2020;63:4790–4810. doi: 10.1021/acs.jmedchem.0c00015. PubMed DOI PMC
Zhang X., Sun L., Meuser M.E., Zalloum W.A., Xu S., Huang T., Cherukupalli S., Jiang X., Ding X., Tao Y., et al. Design, synthesis, and mechanism study of dimerized phenylalanine derivatives as novel HIV-1 capsid inhibitors. Eur. J. Med. Chem. 2021;226:113848. doi: 10.1016/j.ejmech.2021.113848. PubMed DOI PMC
Kortagere S., Welsh W.J. Development and application of hybrid structure based method for efficient screening of ligands binding to G-protein coupled receptors. J. Comput. Aided Mol. Des. 2006;20:789–802. doi: 10.1007/s10822-006-9077-8. PubMed DOI PMC
Kortagere S., Madani N., Mankowski M.K., Schön A., Zentner I., Swaminathan G., Princiotto A., Anthony K., Oza A., Sierra L.J., et al. Inhibiting early-stage events in HIV-1 replication by small-molecule targeting of the HIV-1 capsid. J. Virol. 2012;86:8472–8481. doi: 10.1128/JVI.05006-11. PubMed DOI PMC
Long M., Cantrelle F.X., Robert X., Boll E., Sierra N., Gouet P., Hanoulle X., Alvarez G.I., Guillon C. Identification of a potential inhibitor of the FIV p24 capsid protein and characterization of its binding site. Biochemistry. 2021;60:1896–1908. doi: 10.1021/acs.biochem.1c00228. PubMed DOI
Irwin J.J., Shoichet B.K. ZINC—A free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 2005;45:177–182. doi: 10.1021/ci049714+. PubMed DOI PMC
Curreli F., Zhang H., Zhang X., Pyatkin I., Victor Z., Altieri A., Debnath A.K. Virtual screening based identification of novel small-molecule inhibitors targeted to the HIV-1 capsid. Bioorg. Med. Chem. 2011;19:77–90. doi: 10.1016/j.bmc.2010.11.045. PubMed DOI PMC
Thenin-Houssier S., de Vera I.M., Pedro-Rosa L., Brady A., Richard A., Konnick B., Opp S., Buffone C., Fuhrmann J., Kota S., et al. Ebselen, a small-molecule capsid inhibitor of HIV-1 replication. Antimicrob. Agents Chemother. 2016;60:2195–2208. doi: 10.1128/AAC.02574-15. PubMed DOI PMC
Sakurai T., Kanayama M., Shibata T., Itoh K., Kobayashi A., Yamamoto M., Uchida K. Ebselen, a seleno-organic antioxidant, as an electrophile. Chem. Res. Toxicol. 2006;19:1196–1204. doi: 10.1021/tx0601105. PubMed DOI
Lampel A., Bram Y., Ezer A., Shaltiel-Kario R., Saad J.S., Bacharach E., Gazit E. Targeting the early step of building block organization in viral capsid assembly. ACS Chem. Biol. 2015;10:1785–1790. doi: 10.1021/acschembio.5b00347. PubMed DOI
Zhang D.W., Luo R.H., Xu L., Yang L.M., Xu X.S., Bedwell G.J., Engelman A.N., Zheng Y.T., Chang S. A HTRF based competitive binding assay for screening specific inhibitors of HIV-1 capsid assembly targeting the C-terminal domain of capsid. Antivir. Res. 2019;169:104544. doi: 10.1016/j.antiviral.2019.104544. PubMed DOI PMC
Fujioka T., Kashiwada Y., Kilkuskie R.E., Cosentino L.M., Ballas L.M., Jiang J.B., Janzen W.P., Chen I.S., Lee K.H. Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids. J. Nat. Prod. 1994;57:243–247. doi: 10.1021/np50104a008. PubMed DOI
Keller P.W., Adamson C.S., Heymann J.B., Freed E.O., Steven A.C. HIV-1 maturation inhibitor bevirimat stabilizes the immature Gag lattice. J. Virol. 2011;85:1420–1428. doi: 10.1128/JVI.01926-10. PubMed DOI PMC
Nguyen A.T., Feasley C.L., Jackson K.W., Nitz T.J., Salzwedel K., Air G.M., Sakalian M. The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage site in immature Gag particles. Retrovirology. 2011;8:101. doi: 10.1186/1742-4690-8-101. PubMed DOI PMC
Li F., Goila-Gaur R., Salzwedel K., Kilgore N.R., Reddick M., Matallana C., Castillo A., Zoumplis D., Martin D.E., Orenstein J.M., et al. PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc. Natl. Acad. Sci. USA. 2003;100:13555–13560. doi: 10.1073/pnas.2234683100. PubMed DOI PMC
Bullock P., Larsen D., Press R., Wehrman T., Martin D.E. The absorption, distribution, metabolism and elimination of bevirimat in rats. Biopharm. Drug Dispos. 2008;29:396–405. doi: 10.1002/bdd.625. PubMed DOI
Smith P.F., Ogundele A., Forrest A., Wilton J., Salzwedel K., Doto J., Allaway G.P., Martin D.E. Phase I and II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single-dose 3-o-(3′,3′-dimethylsuccinyl)betulinic acid (bevirimat) against human immunodeficiency virus infection. Antimicrob. Agents Chemother. 2007;51:3574–3581. doi: 10.1128/AAC.00152-07. PubMed DOI PMC
Van Baelen K., Salzwedel K., Rondelez E., Van Eygen V., De Vos S., Verheyen A., Steegen K., Verlinden Y., Allaway G.P., Stuyver L.J. Susceptibility of human immunodeficiency virus type 1 to the maturation inhibitor bevirimat is modulated by baseline polymorphisms in Gag spacer peptide 1. Antimicrob. Agents Chemother. 2009;53:2185–2188. doi: 10.1128/AAC.01650-08. PubMed DOI PMC
Margot N.A., Gibbs C.S., Miller M.D. Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat. Antimicrob. Agents Chemother. 2010;54:2345–2353. doi: 10.1128/AAC.01784-09. PubMed DOI PMC
Knapp D.J., Harrigan P.R., Poon A.F., Brumme Z.L., Brockman M., Cheung P.K. In vitro selection of clinically relevant bevirimat resistance mutations revealed by “deep” sequencing of serially passaged, quasispecies-containing recombinant HIV-1. J. Clin. Microbiol. 2011;49:201–208. doi: 10.1128/JCM.01868-10. PubMed DOI PMC
Reed J.C., Solas D., Kitaygorodskyy A., Freeman B., Ressler D.T.B., Phuong D.J., Swain J.V., Matlack K., Hurt C.R., Lingappa V.R., et al. Identification of an antiretroviral small molecule that appears to be a host-targeting inhibitor of HIV-1 assembly. J. Virol. 2021;95 doi: 10.1128/JVI.00883-20. PubMed DOI PMC
Teow S.Y., Mualif S.A., Omar T.C., Wei C.Y., Yusoff N.M., Ali S.A. Production and purification of polymerization-competent HIV-1 capsid protein p24 (CA) in NiCo21(DE3) Escherichia coli. BMC Biotechnol. 2013;13:107. doi: 10.1186/1472-6750-13-107. PubMed DOI PMC
Ali S.A., Teow S.Y., Omar T.C., Khoo A.S., Choon T.S., Yusoff N.M. A cell internalizing antibody targeting capsid protein (p24) inhibits the replication of HIV-1 in T cells lines and PBMCs: A proof of concept study. PLoS ONE. 2016;11:e0145986. doi: 10.1371/journal.pone.0145986. PubMed DOI PMC
Munyendo W.L., Lv H., Benza-Ingoula H., Baraza L.D., Zhou J. Cell penetrating peptides in the delivery of biopharmaceuticals. Biomolecules. 2012;2:187–202. doi: 10.3390/biom2020187. PubMed DOI PMC
Zhao Y., Lou D., Burkett J., Kohler H. Chemical engineering of cell penetrating antibodies. J. Immunol. Methods. 2001;254:137–145. doi: 10.1016/S0022-1759(01)00410-0. PubMed DOI
Hashimoto F., Kashiwada Y., Cosentino L.M., Chen C.H., Garrett P.E., Lee K.H. Anti-AIDS agents—XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives. Bioorg. Med. Chem. 1997;5:2133–2143. doi: 10.1016/S0968-0896(97)00158-2. PubMed DOI
Prifti G.M., Moianos D., Giannakopoulou E., Pardali V., Tavis J.E., Zoidis G. Recent advances in hepatitis B treatment. Pharmaceuticals. 2021;14:417. doi: 10.3390/ph14050417. PubMed DOI PMC
Tsounis E.P., Tourkochristou E., Mouzaki A., Triantos C. Toward a new era of hepatitis B virus therapeutics: The pursuit of a functional cure. World J. Gastroenterol. 2021;27:2727–2757. doi: 10.3748/wjg.v27.i21.2727. PubMed DOI PMC
Tsukuda S., Watashi K. Hepatitis B virus biology and life cycle. Antivir. Res. 2020;182:104925. doi: 10.1016/j.antiviral.2020.104925. PubMed DOI
Conway J.F., Cheng N., Zlotnick A., Wingfield P.T., Stahl S.J., Steven A.C. Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy. Nature. 1997;386:91–94. doi: 10.1038/386091a0. PubMed DOI
Packianathan C., Katen S.P., Dann C.E., 3rd, Zlotnick A. Conformational changes in the hepatitis B virus core protein are consistent with a role for allostery in virus assembly. J. Virol. 2010;84:1607–1615. doi: 10.1128/JVI.02033-09. PubMed DOI PMC
Liu C., Fan G., Wang Z., Chen H.S., Yin C.C. Allosteric conformational changes of human HBV core protein transform its assembly. Sci. Rep. 2017;7:1404. doi: 10.1038/s41598-017-01568-9. PubMed DOI PMC
Nijampatnam B., Liotta D.C. Recent advances in the development of HBV capsid assembly modulators. Curr. Opin. Chem. Biol. 2019;50:73–79. doi: 10.1016/j.cbpa.2019.02.009. PubMed DOI
Dane D.S., Cameron C.H., Briggs M. Virus-like particles in serum of patients with Australia-antigen associated hepatitis. Lancet. 1970;295:695–698. doi: 10.1016/S0140-6736(70)90926-8. PubMed DOI
Viswanathan U., Mani N., Hu Z., Ban H., Du Y., Hu J., Chang J., Guo J.T. Targeting the multifunctional HBV core protein as a potential cure for chronic hepatitis B. Antivir. Res. 2020;182:104917. doi: 10.1016/j.antiviral.2020.104917. PubMed DOI PMC
Yang L., Liu F., Tong X., Hoffmann D., Zuo J., Lu M. Treatment of chronic hepatitis B virus infection using small molecule modulators of nucleocapsid assembly: Recent advances and perspectives. ACS Infect. Dis. 2019;5:713–724. doi: 10.1021/acsinfecdis.8b00337. PubMed DOI
Bassit L., Ono S.K., Schinazi R.F. Moving fast toward hepatitis B virus elimination. Adv. Exp. Med. Biol. 2021;1322:115–138. PubMed PMC
Stray S.J., Zlotnick A. BAY 41-4109 has multiple effects on hepatitis B virus capsid assembly. J. Mol. Recognit. 2006;19:542–548. doi: 10.1002/jmr.801. PubMed DOI
Deres K., Schröder C.H., Paessens A., Goldmann S., Hacker H.J., Weber O., Krämer T., Niewöhner U., Pleiss U., Stoltefuss J., et al. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science. 2003;299:893–896. doi: 10.1126/science.1077215. PubMed DOI
Stray S.J., Bourne C.R., Punna S., Lewis W.G., Finn M.G., Zlotnick A. A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly. Proc. Natl. Acad. Sci. USA. 2005;102:8138–8143. doi: 10.1073/pnas.0409732102. PubMed DOI PMC
Cole A.G. Modulators of HBV capsid assembly as an approach to treating hepatitis B virus infection. Curr. Opin. Pharmacol. 2016;30:131–137. doi: 10.1016/j.coph.2016.08.004. PubMed DOI
Campagna M.R., Liu F., Mao R., Mills C., Cai D., Guo F., Zhao X., Ye H., Cuconati A., Guo H., et al. Sulfamoylbenzamide derivatives inhibit the assembly of hepatitis B virus nucleocapsids. J. Virol. 2013;87:6931–6942. doi: 10.1128/JVI.00582-13. PubMed DOI PMC
Qiu Z., Lin X., Zhang W., Zhou M., Guo L., Kocer B., Wu G., Zhang Z., Liu H., Shi H., et al. Discovery and pre-clinical characterization of third-generation 4-H heteroaryldihydropyrimidine (HAP) analogues as hepatitis B virus (HBV) capsid inhibitors. J. Med. Chem. 2017;60:3352–3371. doi: 10.1021/acs.jmedchem.7b00083. PubMed DOI
Zhang X., Cheng J., Ma J., Hu Z., Wu S., Hwang N., Kulp J., Du Y., Guo J.-T., Chang J. Discovery of novel hepatitis B virus nucleocapsid assembly inhibitors. ACS Infect. Dis. 2019;5:759–768. doi: 10.1021/acsinfecdis.8b00269. PubMed DOI PMC
Billioud G., Pichoud C., Puerstinger G., Neyts J., Zoulim F. The main hepatitis B virus (HBV) mutants resistant to nucleoside analogs are susceptible in vitro to non-nucleoside inhibitors of HBV replication. Antivir. Res. 2011;92:271–276. doi: 10.1016/j.antiviral.2011.08.012. PubMed DOI
Yan Z., Wu D., Hu H., Zeng J., Yu X., Xu Z., Zhou Z., Zhou X., Yang G., Young J.A.T., et al. Direct inhibition of hepatitis B e antigen by core protein allosteric modulator. Hepatology. 2019;70:11–24. doi: 10.1002/hep.30514. PubMed DOI PMC
Feld J.J., Colledge D., Sozzi V., Edwards R., Littlejohn M., Locarnini S.A. The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging. Antivir. Res. 2007;76:168–177. doi: 10.1016/j.antiviral.2007.06.014. PubMed DOI
Zhou Z., Hu T., Zhou X., Wildum S., Garcia-Alcalde F., Xu B., Wu D., Mao Y., Tian X., Zhou Y., et al. Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) inhibit hepatitis B virus replication by different molecular mechanisms. Sci. Rep. 2017;7:42374. doi: 10.1038/srep42374. PubMed DOI PMC
Klumpp K., Shimada T., Allweiss L., Volz T., Lütgehetmann M., Hartman G., Flores O.A., Lam A.M., Dandri M. Efficacy of NVR 3-778, alone and in combination with pegylated interferon, vs. Entecavir in uPA/SCID mice with humanized livers and HBV infection. Gastroenterology. 2018;154:652–662.e8. doi: 10.1053/j.gastro.2017.10.017. PubMed DOI
Aktoudianakis E.R.C., Canales E., Currie K.S., Kato D., Li J., Link J.O., Metobo S.E., Saito R.D., Schroeder S.D., Shapiro N., et al. Compounds for the Treatment of Hepatitis B Virus Infections. Application No. 20180251460. U.S. Patent. 2017 February 2;
Gane E., Liu A., Yuen M.F., Schwabe C., Bo Q., Das S., Gao L., Zhou X., Wang Y., Coakley E., et al. LBO-003-RO7049389, a core protein allosteric modulator, demonstrates robust anti-HBV activity in chronic hepatitis B patients and is safe and well tolerated. J. Hepatol. 2018;68:S101. doi: 10.1016/S0168-8278(18)30422-7. DOI
Feng S., Gane E., Schwabe C., Zhu M., Triyatni M., Zhou J., Bo Q., Jin Y. A five-in-one first-in-human study to assess safety, tolerability, and pharmacokinetics of RO7049389, an inhibitor of hepatitis B virus capsid assembly, after single and multiple ascending doses in healthy participants. Antimicrob. Agents Chemother. 2020;64 doi: 10.1128/AAC.01323-20. PubMed DOI PMC
Na H.G., Imran A., Kim K., Han H.S., Lee Y.J., Kim M.-J., Yun C.-S., Jung Y.-S., Lee J.-Y., Han S.B. Discovery of a new sulfonamide hepatitis B capsid assembly modulator. ACS Med. Chem. Lett. 2020;11:166–171. doi: 10.1021/acsmedchemlett.9b00550. PubMed DOI PMC
Lee Y.H., Cha H.-M., Hwang J.Y., Park S.Y., Vishakantegowda A.G., Imran A., Lee J.-Y., Yi Y.-S., Jun S., Kim G.H., et al. Sulfamoylbenzamide-based capsid assembly modulators for selective inhibition of hepatitis B viral replication. ACS Med. Chem. Lett. 2021;12:242–248. doi: 10.1021/acsmedchemlett.0c00606. PubMed DOI PMC
Sari O., Boucle S., Cox B.D., Ozturk T., Russell O.O., Bassit L., Amblard F., Schinazi R.F. Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector. Eur. J. Med. Chem. 2017;138:407–421. doi: 10.1016/j.ejmech.2017.06.062. PubMed DOI PMC
Hurwitz S.J., McBrearty N., Arzumanyan A., Bichenkov E., Tao S., Bassit L., Chen Z., Kohler J.J., Amblard F., Feitelson M.A., et al. Studies on the efficacy, potential cardiotoxicity and monkey pharmacokinetics of GLP-26 as a potent hepatitis B virus capsid assembly modulator. Viruses. 2021;13:114. doi: 10.3390/v13010114. PubMed DOI PMC
Amblard F., Boucle S., Bassit L., Cox B., Sari O., Tao S., Chen Z., Ozturk T., Verma K., Russell O., et al. Novel hepatitis B virus capsid assembly modulator induces potent antiviral responses in vitro and in humanized mice. Antimicrob. Agents Chemother. 2020;64:e01701-19. doi: 10.1128/AAC.01701-19. PubMed DOI PMC
Pan T., Ding Y., Wu L., Liang L., He X., Li Q., Bai C., Zhang H. Design and synthesis of aminothiazole based hepatitis B virus (HBV) capsid inhibitors. Eur. J. Med. Chem. 2019;166:480–501. doi: 10.1016/j.ejmech.2019.01.059. PubMed DOI
Lv K., Wu S., Li W., Geng Y., Wu M., Zhou J., Li Y., Gao Q., Liu M. Design, synthesis and anti-HBV activity of NVR3-778 derivatives. Bioorg. Chem. 2020;94:103363. doi: 10.1016/j.bioorg.2019.103363. PubMed DOI
Song L.T., Liu R.R., Zhai H.L., Meng Y.J., Zhu M. Molecular mechanisms of tetrahydropyrrolo[1,2-c]pyrimidines as HBV capsid assembly inhibitors. Arch. Biochem. Biophys. 2019;663:1–10. doi: 10.1016/j.abb.2018.12.029. PubMed DOI
Vandyck K., Rombouts G., Stoops B., Tahri A., Vos A., Verschueren W., Wu Y., Yang J., Hou F., Huang B., et al. Synthesis and evaluation of N-phenyl-3-sulfamoyl-benzamide derivatives as capsid assembly modulators inhibiting hepatitis B virus (HBV) J. Med. Chem. 2018;61:6247–6260. doi: 10.1021/acs.jmedchem.8b00654. PubMed DOI
Tu J., Li J.J., Shan Z.J., Zhai H.L. Exploring the binding mechanism of heteroaryldihydropyrimidines and hepatitis B virus capsid combined 3D-QSAR and molecular dynamics. Antivir. Res. 2017;137:151–164. doi: 10.1016/j.antiviral.2016.11.026. PubMed DOI
Hwang N., Ban H., Chen J., Ma J., Liu H., Lam P., Kulp J., Menne S., Chang J., Guo J.T., et al. Synthesis of 4-oxotetrahydropyrimidine-1(2H)-carboxamides derivatives as capsid assembly modulators of hepatitis B virus. Med. Chem. Res. 2021;30:459–472. doi: 10.1007/s00044-020-02677-3. PubMed DOI PMC
Jia H., Yu J., Du X., Cherukupalli S., Zhan P., Liu X. Design, diversity-oriented synthesis and biological evaluation of novel heterocycle derivatives as non-nucleoside HBV capsid protein inhibitors. Eur. J. Med. Chem. 2020;202:112495. doi: 10.1016/j.ejmech.2020.112495. PubMed DOI
Yang L., Shi L., Chen H., Tong X., Wang G., Zhang Y., Wang W., Feng C., He P., Zhu F., et al. Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation. Acta Pharmacol. Sin. 2014;35:410–418. doi: 10.1038/aps.2013.175. PubMed DOI PMC
Jia H., Bai F., Liu N., Liang X., Zhan P., Ma C., Jiang X., Liu X. Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside hepatitis B virus inhibitors. Eur. J. Med. Chem. 2016;123:202–210. doi: 10.1016/j.ejmech.2016.07.048. PubMed DOI
Toyama M., Sakakibara N., Takeda M., Okamoto M., Watashi K., Wakita T., Sugiyama M., Mizokami M., Ikeda M., Baba M. Pyrimidotriazine derivatives as selective inhibitors of HBV capsid assembly. Virus Res. 2019;271:197677. doi: 10.1016/j.virusres.2019.197677. PubMed DOI
Kuduk S.D., Stoops B., Alexander R., Lam A.M., Espiritu C., Vogel R., Lau V., Klumpp K., Flores O.A., Hartman G.D. Identification of a new class of HBV capsid assembly modulator. Bioorg. Med. Chem. Lett. 2021;39:127848. doi: 10.1016/j.bmcl.2021.127848. PubMed DOI
Wang Y., Wang Z., Liu J., Wang Y., Wu R., Sheng R., Hou T. Discovery of novel HBV capsid assembly modulators by structure-based virtual screening and bioassays. Bioorg. Med. Chem. 2021;36:116096. doi: 10.1016/j.bmc.2021.116096. PubMed DOI
Yamasaki M., Matsuda N., Matoba K., Kondo S., Kanegae Y., Saito I., Nomoto A. Acetophenone 4-nitrophenylhydrazone inhibits Hepatitis B virus replication by modulating capsid assembly. Virus Res. 2021;306:198565. doi: 10.1016/j.virusres.2021.198565. PubMed DOI
Klumpp K., Lam A.M., Lukacs C., Vogel R., Ren S., Espiritu C., Baydo R., Atkins K., Abendroth J., Liao G., et al. High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein. Proc. Natl. Acad. Sci. USA. 2015;112:15196. doi: 10.1073/pnas.1513803112. PubMed DOI PMC
Delaney William E., Edwards R., Colledge D., Shaw T., Furman P., Painter G., Locarnini S. Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type and Lamivudine-resistant strains of hepatitis B virus in vitro. Antimicrob. Agents Chemother. 2002;46:3057–3060. doi: 10.1128/AAC.46.9.3057-3060.2002. PubMed DOI PMC
Kim H., Ko C., Lee J.-Y., Kim M. Current progress in the development of hepatitis B virus capsid assembly modulators: Chemical structure, mode-of-action and efficacy. Molecules. 2021;26:7420. doi: 10.3390/molecules26247420. PubMed DOI PMC
Lohmann V. Hepatitis C virus RNA replication. Curr. Top Microbiol. Immunol. 2013;369:167–198. PubMed PMC
Morozov V.A., Lagaye S. Hepatitis C virus: Morphogenesis, infection and therapy. World J. Hepatol. 2018;10:186–212. doi: 10.4254/wjh.v10.i2.186. PubMed DOI PMC
Rogers M.E., Balistreri W.F. Cascade of care for children and adolescents with chronic hepatitis C. World J. Gastroenterol. 2021;27:1117–1131. doi: 10.3748/wjg.v27.i12.1117. PubMed DOI PMC
Manns M.P., McHutchison J.G., Gordon S.C., Rustgi V.K., Shiffman M., Reindollar R., Goodman Z.D., Koury K., Ling M., Albrecht J.K. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial. Lancet. 2001;358:958–965. doi: 10.1016/S0140-6736(01)06102-5. PubMed DOI
Zeng H., Li L., Hou Z., Zhang Y., Tang Z., Liu S. Direct-acting antiviral in the treatment of chronic hepatitis C: Bonuses and challenges. Int. J. Med. Sci. 2020;17:892–902. doi: 10.7150/ijms.43079. PubMed DOI PMC
Lawitz E., Jacobson I.M., Nelson D.R., Zeuzem S., Sulkowski M.S., Esteban R., Brainard D., McNally J., Symonds W.T., McHutchison J.G., et al. Development of sofosbuvir for the treatment of hepatitis C virus infection. Ann. N. Y. Acad. Sci. 2015;1358:56–67. doi: 10.1111/nyas.12832. PubMed DOI
Shirota Y., Luo H., Qin W., Kaneko S., Yamashita T., Kobayashi K., Murakami S. Hepatitis C virus (HCV) NS5A binds RNA-dependent RNA polymerase (RdRP) NS5B and modulates RNA-dependent RNA polymerase activity. J. Biol. Chem. 2002;277:11149–11155. doi: 10.1074/jbc.M111392200. PubMed DOI
Lange C.M., Jacobson I.M., Rice C.M., Zeuzem S. Emerging therapies for the treatment of hepatitis C. EMBO Mol. Med. 2014;6:4–15. doi: 10.1002/emmm.201303131. PubMed DOI PMC
Mukherjee S., Hanson A.M., Shadrick W.R., Ndjomou J., Sweeney N.L., Hernandez J.J., Bartczak D., Li K., Frankowski K.J., Heck J.A., et al. Identification and analysis of hepatitis C virus NS3 helicase inhibitors using nucleic acid binding assays. Nucleic Acids Res. 2012;40:8607–8621. doi: 10.1093/nar/gks623. PubMed DOI PMC
Hofmann S., Krajewski M., Scherer C., Scholz V., Mordhorst V., Truschow P., Schöbel A., Reimer R., Schwudke D., Herker E. Complex lipid metabolic remodeling is required for efficient hepatitis C virus replication. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2018;1863:1041–1056. doi: 10.1016/j.bbalip.2018.06.002. PubMed DOI
Hu L., Li J., Cai H., Yao W., Xiao J., Li Y.-P., Qiu X., Xia H., Peng T. Avasimibe: A novel hepatitis C virus inhibitor that targets the assembly of infectious viral particles. Antivir. Res. 2017;148:5–14. PubMed
André P., Perlemuter G., Budkowska A., Bréchot C., Lotteau V. Hepatitis C virus particles and lipoprotein metabolism. Semin. Liver Dis. 2005;25:93–104. doi: 10.1055/s-2005-864785. PubMed DOI
Sarhan M.A., Abdel-Hakeem M.S., Mason A.L., Tyrrell D.L., Houghton M. Glycogen synthase kinase 3β inhibitors prevent hepatitis C virus release/assembly through perturbation of lipid metabolism. Sci. Rep. 2017;7:2495. doi: 10.1038/s41598-017-02648-6. PubMed DOI PMC
Khachatoorian R., Riahi R., Ganapathy E., Shao H., Wheatley N.M., Sundberg C., Jung C.L., Ruchala P., Dasgupta A., Arumugaswami V., et al. Allosteric heat shock protein 70 inhibitors block hepatitis C virus assembly. Int. J. Antimicrob. Agents. 2016;47:289–296. doi: 10.1016/j.ijantimicag.2016.01.012. PubMed DOI PMC
Parent R., Qu X., Petit M.A., Beretta L. The heat shock cognate protein 70 is associated with hepatitis C virus particles and modulates virus infectivity. Hepatology. 2009;49:1798–1809. doi: 10.1002/hep.22852. PubMed DOI PMC
Wang Z., Li Y., Yang X., Zhao J., Cheng Y., Wang J. Mechanism and complex roles of HSC70 in viral infections. Front. Microbiol. 2020;11:1577. doi: 10.3389/fmicb.2020.01577. PubMed DOI PMC
Meanwell N.A., Belema M. The discovery and development of daclatasvir: An inhibitor of the hepatitis C virus NS5A replication complex. HCV J. Discov. Cure. 2018;32:27–55.
Boson B., Denolly S., Turlure F., Chamot C., Dreux M., Cosset F.L. Daclatasvir prevents hepatitis C virus infectivity by blocking transfer of the viral genome to assembly sites. Gastroenterology. 2017;152:895–907.e14. doi: 10.1053/j.gastro.2016.11.047. PubMed DOI
Hu Z., Hu X., He S., Yim H.J., Xiao J., Swaroop M., Tanega C., Zhang Y.Q., Yi G., Kao C.C., et al. Identification of novel anti-hepatitis C virus agents by a quantitative high throughput screen in a cell-based infection assay. Antivir. Res. 2015;124:20–29. doi: 10.1016/j.antiviral.2015.10.018. PubMed DOI PMC
Park S.B., Boyer A., Hu Z., Le D., Liang T.J. Discovery and characterization of a novel HCV inhibitor targeting the late stage of HCV life cycle. Antivir. Ther. 2019;24:371–381. doi: 10.3851/IMP3303. PubMed DOI PMC
Neveu G., Barouch-Bentov R., Ziv-Av A., Gerber D., Jacob Y., Einav S. Identification and targeting of an interaction between a tyrosine motif within hepatitis C virus core protein and AP2M1 essential for viral assembly. PLoS Pathog. 2012;8:e1002845. doi: 10.1371/journal.ppat.1002845. PubMed DOI PMC
Ma C.D., Imamura M., Talley D.C., Rolt A., Xu X., Wang A.Q., Le D., Uchida T., Osawa M., Teraoka Y., et al. Fluoxazolevir inhibits hepatitis C virus infection in humanized chimeric mice by blocking viral membrane fusion. Nat. Microbiol. 2020;5:1532–1541. doi: 10.1038/s41564-020-0781-2. PubMed DOI PMC
He S., Lin B., Chu V., Hu Z., Hu X., Xiao J., Wang A.Q., Schweitzer C.J., Li Q., Imamura M., et al. Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection. Sci. Transl. Med. 2015;7:282ra49. doi: 10.1126/scitranslmed.3010286. PubMed DOI PMC
Rolt A., Le D., Hu Z., Wang A.Q., Shah P., Singleton M., Hughes E., Dulcey A.E., He S., Imamura M., et al. Preclinical pharmacological development of chlorcyclizine derivatives for the treatment of hepatitis C virus infection. J. Infect. Dis. 2018;217:1761–1769. doi: 10.1093/infdis/jiy039. PubMed DOI PMC
Rolt A., Talley D.C., Park S.B., Hu Z., Dulcey A., Ma C., Irvin P., Leek M., Wang A.Q., Stachulski A.V., et al. Discovery and optimization of a 4-aminopiperidine scaffold for inhibition of hepatitis C virus assembly. J. Med. Chem. 2021;64:9431–9443. doi: 10.1021/acs.jmedchem.1c00696. PubMed DOI PMC
Kota S., Coito C., Mousseau G., Lavergne J.P., Strosberg A.D. Peptide inhibitors of hepatitis C virus core oligomerization and virus production. Pt 6J. Gen. Virol. 2009;90:1319–1328. doi: 10.1099/vir.0.008565-0. PubMed DOI
Kota S., Scampavia L., Spicer T., Beeler A.B., Takahashi V., Snyder J.K., Porco J.A., Hodder P., Strosberg A.D. A time-resolved fluorescence–resonance energy transfer assay for identifying inhibitors of hepatitis C virus core dimerization. Assay Drug Dev. Technol. 2009;8:96–105. doi: 10.1089/adt.2009.0217. PubMed DOI PMC
Ni F., Kota S., Takahashi V., Strosberg A.D., Snyder J.K. Potent inhibitors of hepatitis C core dimerization as new leads for anti-hepatitis C agents. Bioorg. Med. Chem. Lett. 2011;21:2198–2202. doi: 10.1016/j.bmcl.2011.03.014. PubMed DOI PMC
Kota S., Takahashi V., Ni F., Snyder J.K., Strosberg A.D. Direct binding of a hepatitis C virus inhibitor to the viral capsid protein. PLoS ONE. 2012;7:e32207. doi: 10.1371/journal.pone.0032207. PubMed DOI PMC
Bhatt S., Gething P.W., Brady O.J., Messina J.P., Farlow A.W., Moyes C.L., Drake J.M., Brownstein J.S., Hoen A.G., Sankoh O., et al. The global distribution and burden of dengue. Nature. 2013;496:504–507. doi: 10.1038/nature12060. PubMed DOI PMC
Gwee S.X.W., St John A.L., Gray G.C., Pang J. Animals as potential reservoirs for dengue transmission: A systematic review. One Health. 2021;12:100216. doi: 10.1016/j.onehlt.2021.100216. PubMed DOI PMC
Tian Y.S., Zhou Y., Takagi T., Kameoka M., Kawashita N. Dengue virus and its inhibitors: A brief review. Chem. Pharm. Bull. 2018;66:191–206. doi: 10.1248/cpb.c17-00794. PubMed DOI
Byrd C.M., Dai D., Grosenbach D.W., Berhanu A., Jones K.F., Cardwell K.B., Schneider C., Wineinger K.A., Page J.M., Harver C., et al. A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob. Agents Chemother. 2013;57:15–25. doi: 10.1128/AAC.01429-12. PubMed DOI PMC
Scaturro P., Trist I.M.L., Paul D., Kumar A., Acosta E.G., Byrd C.M., Jordan R., Brancale A., Bartenschlager R., Diamond M.S. Characterization of the mode of action of a potent dengue virus capsid inhibitor. J. Virol. 2014;88:11540–11555. doi: 10.1128/JVI.01745-14. PubMed DOI PMC
Shum D., Smith J.L., Hirsch A.J., Bhinder B., Radu C., Stein D.A., Nelson J.A., Früh K., Djaballah H. High-content assay to identify inhibitors of dengue virus infection. Assay Drug Dev. Technol. 2010;8:553–570. doi: 10.1089/adt.2010.0321. PubMed DOI PMC
Smith J.L., Sheridan K., Parkins C.J., Frueh L., Jemison A.L., Strode K., Dow G., Nilsen A., Hirsch A.J. Characterization and structure-activity relationship analysis of a class of antiviral compounds that directly bind dengue virus capsid protein and are incorporated into virions. Antivir. Res. 2018;155:12–19. doi: 10.1016/j.antiviral.2018.04.019. PubMed DOI PMC
Mousseau G., Kota S., Takahashi V., Frick D.N., Strosberg A.D. Dimerization-driven interaction of hepatitis C virus core protein with NS3 helicase. J. Gen. Virol. 2011;92:101–111. doi: 10.1099/vir.0.023325-0. PubMed DOI PMC
Arya R., Kumari S., Pandey B., Mistry H., Bihani S.C., Das A., Prashar V., Gupta G.D., Panicker L., Kumar M. Structural insights into SARS-CoV-2 proteins. J. Mol. Biol. 2021;433:166725. doi: 10.1016/j.jmb.2020.11.024. PubMed DOI PMC
Mahtarin R., Islam S., Islam M.J., Ullah M.O., Ali M.A., Halim M.A. Structure and dynamics of membrane protein in SARS-CoV-2. J. Biomol. Struct. Dyn. 2020:1–14. doi: 10.1080/07391102.2020.1861983. PubMed DOI PMC
Peng Y., Du N., Lei Y., Dorje S., Qi J., Luo T., Gao G.F., Song H. Structures of the SARS-CoV-2 nucleocapsid and their perspectives for drug design. EMBO J. 2020;39:e105938. doi: 10.15252/embj.2020105938. PubMed DOI PMC
Zinzula L., Basquin J., Bohn S., Beck F., Klumpe S., Pfeifer G., Nagy I., Bracher A., Hartl F.U., Baumeister W. High-resolution structure and biophysical characterization of the nucleocapsid phosphoprotein dimerization domain from the Covid-19 severe acute respiratory syndrome coronavirus 2. Biochem. Biophys. Res. Commun. 2021;538:54–62. doi: 10.1016/j.bbrc.2020.09.131. PubMed DOI PMC
Korn S.M., Lambertz R., Fürtig B., Hengesbach M., Löhr F., Richter C., Schwalbe H., Weigand J.E., Wöhnert J., Schlundt A. (1)H, (13)C, and (15)N backbone chemical shift assignments of the C-terminal dimerization domain of SARS-CoV-2 nucleocapsid protein. Biomol. NMR Assign. 2021;15:129–135. doi: 10.1007/s12104-020-09995-y. PubMed DOI PMC
Mandala V.S., McKay M.J., Shcherbakov A.A., Dregni A.J., Kolocouris A., Hong M. Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers. Nat. Struct. Mol. Biol. 2020;27:1202–1208. doi: 10.1038/s41594-020-00536-8. PubMed DOI PMC
Bhowmik D., Nandi R., Jagadeesan R., Kumar N., Prakash A., Kumar D. Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches. Infect. Genet. Evol. 2020;84:104451. doi: 10.1016/j.meegid.2020.104451. PubMed DOI PMC
Lipinski C.A. Lead- and drug-like compounds: The rule-of-five revolution. Drug Discov. Today Technol. 2004;1:337–341. doi: 10.1016/j.ddtec.2004.11.007. PubMed DOI
Ahamad S., Gupta D., Kumar V. Targeting SARS-CoV-2 nucleocapsid oligomerization: Insights from molecular docking and molecular dynamics simulations. J. Biomol. Struct. Dyn. 2020:1–14. doi: 10.1080/07391102.2020.1839563. PubMed DOI PMC
Patocka J., Kuca K., Oleksak P., Nepovimova E., Valis M., Novotny M., Klimova B. Rapamycin: Drug repurposing in SARS-CoV-2 infection. Pharmaceuticals. 2021;14:217. doi: 10.3390/ph14030217. PubMed DOI PMC
Husain A., Byrareddy S.N. Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19. Chem. Biol. Interact. 2020;331:109282. doi: 10.1016/j.cbi.2020.109282. PubMed DOI PMC
Peele K.A., Kumar V., Parate S., Srirama K., Lee K.W., Venkateswarulu T.C. Insilico drug repurposing using FDA approved drugs against Membrane protein of SARS-CoV-2. J. Pharm. Sci. 2021;110:2346–2354. doi: 10.1016/j.xphs.2021.03.004. PubMed DOI PMC
Hu X., Zhou Z., Li F., Xiao Y., Wang Z., Xu J., Dong F., Zheng H., Yu R. The study of antiviral drugs targeting SARS-CoV-2 nucleocapsid and spike proteins through large-scale compound repurposing. Heliyon. 2021;7:e06387. doi: 10.1016/j.heliyon.2021.e06387. PubMed DOI PMC
Lo H.S., Hui K.P.Y., Lai H.M., He X., Khan K.S., Kaur S., Huang J., Li Z., Chan A.K.N., Cheung H.H.Y., et al. Simeprevir potently suppresses SARS-CoV-2 replication and synergizes with remdesivir. ACS Cent. Sci. 2021;7:792–802. doi: 10.1021/acscentsci.0c01186. PubMed DOI PMC
Gammeltoft K.A., Zhou Y., Hernandez C.R.D., Galli A., Offersgaard A., Costa R., Pham L.V., Fahnøe U., Feng S., Scheel T.K.H., et al. Hepatitis C virus protease inhibitors show differential efficacy and interactions with remdesivir for treatment of SARS-CoV-2 in vitro. Antimicrob. Agents Chemother. 2021;65:e02680-20. doi: 10.1128/AAC.02680-20. PubMed DOI PMC
Zhu W., Xu M., Chen C.Z., Guo H., Shen M., Hu X., Shinn P., Klumpp-Thomas C., Michael S.G., Zheng W. Identification of SARS-CoV-2 3CL protease inhibitors by a quantitative high-throughput screening. ACS Pharmacol. Transl. Sci. 2020;3:1008–1016. doi: 10.1021/acsptsci.0c00108. PubMed DOI PMC
Melnick J.L. Portraits of viruses: The picornaviruses. Intervirology. 1983;20:61–100. doi: 10.1159/000149376. PubMed DOI
Anasir M.I., Zarif F., Poh C.L. Antivirals blocking entry of enteroviruses and therapeutic potential. J. Biomed. Sci. 2021;28:10. doi: 10.1186/s12929-021-00708-8. PubMed DOI PMC
Zeichhardt H., Otto M.J., McKinlay M.A., Willingmann P., Habermehl K.O. Inhibition of poliovirus uncoating by disoxaril (WIN 51711) Virology. 1987;160:281–285. doi: 10.1016/0042-6822(87)90075-4. PubMed DOI
Jubelt B., Wilson A.K., Kopka S.L., Guidinger P.L., McKinlay M.A. Clearance of a persistent human enterovirus infection of the mouse central nervous system by the antiviral agent disoxaril. J. Infect. Dis. 1989;159:866–871. doi: 10.1093/infdis/159.5.866. PubMed DOI
Buontempo P.J., Cox S., Wright-Minogue J., DeMartino J.L., Skelton A.M., Ferrari E., Albin R., Rozhon E.J., Girijavallabhan V., Modlin J.F., et al. SCH 48973: A potent, broad-spectrum, antienterovirus compound. Antimicrob. Agents Chemother. 1997;41:1220–1225. doi: 10.1128/AAC.41.6.1220. PubMed DOI PMC
Oberste M.S., Moore D., Anderson B., Pallansch Mark A., Pevear Daniel C., Collett Marc S. In vitro antiviral activity of V-073 against polioviruses. Antimicrob. Agents Chemother. 2009;53:4501–4503. doi: 10.1128/AAC.00671-09. PubMed DOI PMC
Rossmann M.G., He Y., Kuhn R.J. Picornavirus–receptor interactions. Trends Microbiol. 2002;10:324–331. doi: 10.1016/S0966-842X(02)02383-1. PubMed DOI
Diana G.D., McKinlay M.A., Otto M.J., Akullian V., Oglesby C. [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating. J. Med. Chem. 1985;28:1906–1910. doi: 10.1021/jm00150a025. PubMed DOI
Bauer L., Lyoo H., van der Schaar H.M., Strating J.R.P.M., van Kuppeveld F.J.M. Direct-acting antivirals and host-targeting strategies to combat enterovirus infections. Curr. Opin. Virol. 2017;24:1–8. doi: 10.1016/j.coviro.2017.03.009. PubMed DOI PMC
Diana G.D., Salvador U.J., Zalay E.S., Johnson R.E., Collins J.C., Johnson D., Hinshaw W.B., Lorenz R.R., Thielking W.H., Pancic F. Antiviral activity of some beta-diketones. 1. Aryl alkyl diketones. In vitro activity against both RNA and DNA viruses. J. Med. Chem. 1977;20:750–756. doi: 10.1021/jm00216a003. PubMed DOI
Diana G.D., Salvador U.J., Zalay E.S., Carabateas P.M., Williams G.L., Collins J.C., Pancic F. Antiviral activity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity against both RNA and DNA viruses. J. Med. Chem. 1977;20:757–761. doi: 10.1021/jm00216a004. PubMed DOI
Diana G.D., Carabateas P.M., Johnson R.E., Williams G.L., Pancic F., Collins J.C. Antiviral activity of some beta-diketones. 4. Benzyl diketones. In vitro activity against both RNA and DNA viruses. J. Med. Chem. 1978;21:889–894. doi: 10.1021/jm00207a010. PubMed DOI
Diana G.D., Carabateas P.M., Salvador U.J., Williams G.L., Zalay E.S., Pancic F., Steinberg B.A., Collins J.C. Antiviral activity of some beta-diketones. 3. Aryl bis(beta-diketones). Antiherpetic activity. J. Med. Chem. 1978;21:689–692. doi: 10.1021/jm00205a019. PubMed DOI
Egorova A., Ekins S., Schmidtke M., Makarov V. Back to the future: Advances in development of broad-spectrum capsid-binding inhibitors of enteroviruses. Eur. J. Med. Chem. 2019;178:606–622. doi: 10.1016/j.ejmech.2019.06.008. PubMed DOI PMC
McSharry J.J., Caliguiri L.A., Eggers H.J. Inhibition of uncoating of poliovirus by arildone, a new antiviral drug. Virology. 1979;97:307–315. doi: 10.1016/0042-6822(79)90342-8. PubMed DOI
Otto M.J., Fox M.P., Fancher M.J., Kuhrt M.F., Diana G.D., McKinlay M.A. In vitro activity of WIN 51711, a new broad-spectrum antipicornavirus drug. Antimicrob. Agents Chemother. 1985;27:883–886. doi: 10.1128/AAC.27.6.883. PubMed DOI PMC
McKinlay M.A. WIN 51711, a new systematically active broad-spectrum antipicornavirus agent. J. Antimicrob. Chemother. 1985;16:284–286. doi: 10.1093/jac/16.3.284. PubMed DOI
Diana G.D., Cutcliffe D., Oglesby R.C., Otto M.J., Mallamo J.P., Akullian V., McKinlay M.A. Synthesis and structure-activity studies of some disubstituted phenylisoxazoles against human picornavirus. J. Med. Chem. 1989;32:450–455. doi: 10.1021/jm00122a027. PubMed DOI
Smith T.J., Kremer M.J., Luo M., Vriend G., Arnold E., Kamer G., Rossmann M.G., McKinlay M.A., Diana G.D., Otto M.J. The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science. 1986;233:1286–1293. doi: 10.1126/science.3018924. PubMed DOI
Desmond R.A., Accortt N.A., Talley L., Villano S.A., Soong S.J., Whitley R.J. Enteroviral meningitis: Natural history and outcome of pleconaril therapy. Antimicrob. Agents Chemother. 2006;50:2409–2414. doi: 10.1128/AAC.00227-06. PubMed DOI PMC
Hayden F.G., Herrington D.T., Coats T.L., Kim K., Cooper E.C., Villano S.A., Liu S., Hudson S., Pevear D.C., Collett M., et al. Pleconaril respiratory infection study group, Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: Results of 2 double-blind, randomized, placebo-controlled trials. Clin. Infect Dis. 2003;36:1523–1532. doi: 10.1086/375069. PubMed DOI PMC
Shia K.S., Li W.T., Chang C.M., Hsu M.C., Chern J.H., Leong M.K., Tseng S.N., Lee C.C., Lee Y.C., Chen S.J., et al. Design, synthesis, and structure-activity relationship of pyridyl imidazolidinones: A novel class of potent and selective human enterovirus 71 inhibitors. J. Med. Chem. 2002;45:1644–1655. doi: 10.1021/jm010536a. PubMed DOI
Chang C.S., Lin Y.T., Shih S.R., Lee C.C., Lee Y.C., Tai C.L., Tseng S.N., Chern J.H. Design, synthesis, and antipicornavirus activity of 1-[5-(4-Arylphenoxy)alkyl]-3-pyridin-4-ylimidazolidin-2-one derivatives. J. Med. Chem. 2005;48:3522–3535. doi: 10.1021/jm050033v. PubMed DOI
Diana G.D., Treasurywala A.M., Bailey T.R., Oglesby R.C., Pevear D.C., Dutko F.J. A model for compounds active against human rhinovirus-14 based on X-ray crystallography data. J. Med. Chem. 1990;33:1306–1311. doi: 10.1021/jm00167a006. PubMed DOI
Rozhon E., Cox S., Buontempo P., O’Connell J., Slater W., De Martino J., Schwartz J., Miller G., Arnold E., Zhang A., et al. SCH 38057: A picornavirus capsid-binding molecule with antiviral activity after the initial stage of viral uncoating. Antivir. Res. 1993;21:15–35. doi: 10.1016/0166-3542(93)90064-P. PubMed DOI
Collett M.S., Hincks J.R., Benschop K., Duizer E., van der Avoort H., Rhoden E., Liu H., Oberste M.S., McKinlay M.A., Hartford M. Antiviral activity of pocapavir in a randomized, blinded, placebo-controlled human oral poliovirus vaccine challenge model. J. Infect. Dis. 2017;215:335–343. doi: 10.1093/infdis/jiw542. PubMed DOI PMC
Rotbart H.A. Antiviral therapy for enteroviruses and rhinoviruses. Antivir. Chem. Chemother. 2000;11:261–271. doi: 10.1177/095632020001100402. PubMed DOI
Hayden F.G., Hipskind G.J., Woerner D.H., Eisen G.F., Janssens M., Janssen P.A., Andries K. Intranasal pirodavir (R77,975) treatment of rhinovirus colds. Antimicrob. Agents. Chemother. 1995;39:290–294. doi: 10.1128/AAC.39.2.290. PubMed DOI PMC
Mirabelli C., Scheers E., Neyts J. Novel therapeutic approaches to simultaneously target rhinovirus infection and asthma/COPD pathogenesis. F1000Research. 2017;6:1860. PubMed PMC
Feil S.C., Hamilton S., Krippner G.Y., Lin B., Luttick A., McConnell D.B., Nearn R., Parker M.W., Ryan J., Stanislawski P.C., et al. An orally available 3-ethoxybenzisoxazole capsid binder with clinical activity against human rhinovirus. ACS Med. Chem. Lett. 2012;3:303–307. doi: 10.1021/ml2002955. PubMed DOI PMC
Andries K., Dewindt B., De Brabander M., Stokbroekx R., Janssen P.A. In vitro activity of R 61837, a new antirhinovirus compound. Arch. Virol. 1988;101:155–167. PubMed PMC
Aviragen Antiviral Drug Vapendavir Fails Phase IIb Study in Asthma Patients. [(accessed on 20 December 2021)]. Available online: https://www.genengnews.com/topics/drug-discovery/aviragen-antiviral-drug-vapendavir-fails-phase-iib-study-in-asthma-patients/
Rotbart H.A., Webster A.D. Treatment of Potentially Life-Threatening Enterovirus Infections with Pleconaril. Clin. Infect. Dis. 2001;32:228–235. doi: 10.1086/318452. PubMed DOI
Radanović I., Rkman D., Zekan P., Kutleša M., Baršić B. Chronic meningoencephalitis caused by Echo virus 6 in a patient with common variable immunodeficiency. Wien. Klin. Wochenschr. 2018;130:70–72. doi: 10.1007/s00508-017-1289-5. PubMed DOI
Plevka P., Perera R., Yap M.L., Cardosa J., Kuhn R.J., Rossmann M.G. Structure of human enterovirus 71 in complex with a capsid-binding inhibitor. Proc. Natl. Acad. Sci. USA. 2013;110:5463. doi: 10.1073/pnas.1222379110. PubMed DOI PMC
De Colibus L., Wang X., Spyrou J.A.B., Kelly J., Ren J., Grimes J., Puerstinger G., Stonehouse N., Walter T.S., Hu Z., et al. More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules. Nat. Struct. Mol. Biol. 2014;21:282–288. doi: 10.1038/nsmb.2769. PubMed DOI PMC
Wald J., Pasin M., Richter M., Walther C., Mathai N., Kirchmair J., Makarov V.A., Goessweiner-Mohr N., Marlovits T.C., Zanella I., et al. Cryo-EM structure of pleconaril-resistant rhinovirus-B5 complexed to the antiviral OBR-5-340 reveals unexpected binding site. Proc. Natl. Acad. Sci. USA. 2019;116:19109. doi: 10.1073/pnas.1904732116. PubMed DOI PMC
Shih S.R., Tsai M.C., Tseng S.N., Won K.F., Shia K.S., Li W.T., Chern J.H., Chen G.W., Lee C.C., Lee Y.C., et al. Mutation in enterovirus 71 capsid protein VP1 confers resistance to the inhibitory effects of pyridyl imidazolidinone. Antimicrob. Agents Chemother. 2004;48:3523–3529. doi: 10.1128/AAC.48.9.3523-3529.2004. PubMed DOI PMC
Tan Y.W., Yam W.K., Kooi R.J.W., Westman J., Arbrandt G., Chu J.J.H. Novel capsid binder and PI4KIIIbeta inhibitors for EV-A71 replication inhibition. Sci. Rep. 2021;11:9719. doi: 10.1038/s41598-021-89271-8. PubMed DOI PMC
Kim J., Jung Y.K., Kim C., Shin J.S., Scheers E., Lee J.Y., Han S.B., Lee C.K., Neyts J., Ha J.D., et al. A novel series of highly potent small molecule inhibitors of rhinovirus replication. J. Med. Chem. 2017;60:5472–5492. doi: 10.1021/acs.jmedchem.7b00175. PubMed DOI
McLeish Nigel J., Williams Çiğdem H., Kaloudas D., Roivainen Merja M., Stanway G. Symmetry-related clustering of positive charges is a common mechanism for heparan sulfate binding in enteroviruses. J. Virol. 2012;86:11163–11170. doi: 10.1128/JVI.00640-12. PubMed DOI PMC
Nishimura Y., Lee H., Hafenstein S., Kataoka C., Wakita T., Bergelson J.M., Shimizu H. Enterovirus 71 binding to PSGL-1 on leukocytes: VP1-145 acts as a molecular switch to control receptor interaction. PLoS Pathog. 2013;9:e1003511. doi: 10.1371/journal.ppat.1003511. PubMed DOI PMC
Ren P., Zheng Y., Wang W., Hong L., Delpeyroux F., Arenzana-Seisdedos F., Altmeyer R. Suramin interacts with the positively charged region surrounding the 5-fold axis of the EV-A71 capsid and inhibits multiple enterovirus A. Sci. Rep. 2017;7:42902. doi: 10.1038/srep42902. PubMed DOI PMC
Nishimura Y., McLaughlin N.P., Pan J., Goldstein S., Hafenstein S., Shimizu H., Winkler J.D., Bergelson J.M. The suramin derivative NF449 interacts with the 5-fold vertex of the enterovirus A71 capsid to prevent virus attachment to PSGL-1 and heparan sulfate. PLoS Pathog. 2015;11:e1005184. doi: 10.1371/journal.ppat.1005184. PubMed DOI PMC
Rivero-Buceta E., Sun L., Martínez-Gualda B., Doyagüez Elisa G., Donckers K., Quesada E., Camarasa M.-J., Delang L., San-Félix A., Neyts J., et al. Optimization of a class of tryptophan dendrimers that inhibit HIV replication leads to a selective, specific, and low-nanomolar inhibitor of clinical isolates of enterovirus A71. Antimicrob. Agents Chemother. 2016;60:5064–5067. doi: 10.1128/AAC.00626-16. PubMed DOI PMC
Pourianfar H.R., Poh C.L., Fecondo J., Grollo L. In vitro evaluation of the antiviral activity of heparan sulfate mimetic compounds against Enterovirus 71. Virus Res. 2012;169:22–29. doi: 10.1016/j.virusres.2012.06.025. PubMed DOI
Earley D.F., Bailly B., Maggioni A., Kundur A.R., Thomson R.J., Chang C.-W., von Itzstein M. Efficient blocking of enterovirus 71 infection by heparan sulfate analogues acting as decoy receptors. ACS Infect. Dis. 2019;5:1708–1717. doi: 10.1021/acsinfecdis.9b00070. PubMed DOI
Meng T., Jia Q., Wong S.-M., Chua K.-B., López S. In vitro and in vivo inhibition of the infectivity of human enterovirus 71 by a sulfonated food azo dye, brilliant black BN. J. Virol. 2019;93:e00061-19. doi: 10.1128/JVI.00061-19. PubMed DOI PMC
Hsieh C.F., Jheng J.R., Lin G.H., Chen Y.L., Ho J.Y., Liu C.J., Hsu K.Y., Chen Y.S., Chan Y.F., Yu H.M., et al. Rosmarinic acid exhibits broad anti-enterovirus A71 activity by inhibiting the interaction between the five-fold axis of capsid VP1 and cognate sulfated receptors. Emerg. Microb. Infect. 2020;9:1194–1205. doi: 10.1080/22221751.2020.1767512. PubMed DOI PMC
Ma Y., Abdelnabi R., Delang L., Froeyen M., Luyten W., Neyts J., Mirabelli C. New class of early-stage enterovirus inhibitors with a novel mechanism of action. Antivir. Res. 2017;147:67–74. doi: 10.1016/j.antiviral.2017.10.004. PubMed DOI
Abdelnabi R., Geraets J.A., Ma Y., Mirabelli C., Flatt J.W., Domanska A., Delang L., Jochmans D., Kumar T.A., Jayaprakash V., et al. A novel druggable interprotomer pocket in the capsid of rhino- and enteroviruses. PLoS Biol. 2019;17:e3000281. doi: 10.1371/journal.pbio.3000281. PubMed DOI PMC
Bostina M. Monoclonal antibodies point to Achilles’ heel in picornavirus capsid. PLoS Biol. 2019;17:e3000232. doi: 10.1371/journal.pbio.3000232. PubMed DOI PMC
Kelly J.T., De Colibus L., Elliott L., Fry E.E., Stuart D.I., Rowlands D.J., Stonehouse N.J. Potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or Coxsackievirus A16. Antivir. Res. 2015;124:77–82. doi: 10.1016/j.antiviral.2015.10.006. PubMed DOI PMC
Schmidtke M., Hammerschmidt E., Schüler S., Zell R., Birch-Hirschfeld E., Makarov V.A., Riabova O.B., Wutzler P. Susceptibility of coxsackievirus B3 laboratory strains and clinical isolates to the capsid function inhibitor pleconaril: Antiviral studies with virus chimeras demonstrate the crucial role of amino acid 1092 in treatment. J. Antimicrob. Chemother. 2005;56:648–656. doi: 10.1093/jac/dki263. PubMed DOI
Woods M.G., Diana G.D., Rogge M.C., Otto M.J., Dutko F.J., McKinlay M.A. In vitro and in vivo activities of WIN 54954, a new broad-spectrum antipicornavirus drug. Antimicrob. Agents Chemother. 1989;33:2069–2074. doi: 10.1128/AAC.33.12.2069. PubMed DOI PMC
Lanko K., Sun L., Froeyen M., Leyssen P., Delang L., Mirabelli C., Neyts J. Comparative analysis of the molecular mechanism of resistance to vapendavir across a panel of picornavirus species. Antiviral. Res. 2021;195:105177. doi: 10.1016/j.antiviral.2021.105177. PubMed DOI PMC