The 32nd International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held in Baltimore, Maryland, USA, on May 12-15, 2019. This report gives an overview of the conference on behalf of the Society. It provides a general review of the meeting and awardees, summarizing the presentations, and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development. As in past years, ICAR promoted and showcased the most recent progress in antiviral research, and continued to foster collaborations and interactions in drug discovery and development. The 33rd ICAR will be held in Seattle, Washington, USA, March 30th-April 3rd, 2020.

AIDS Research Institute Irsicaixa Hospital Germans Trias 1 Pujol Universitat Autónoma de Barcelona Badalona Spain

Baker Institute Cornell University 235 Hungerford Hill Road Ithaca NY USA

Chevy Chase MD USA

Department of Animal Dairy and Veterinary Sciences Institute for Antiviral Research Utah State University Logan UT USA

Department of Chemistry and Biochemistry University of Maryland Baltimore County Baltimore MD USA

Department of Chemistry Organic Chemistry Faculty of Sciences Universität Hamburg Martin Luther King Platz 6 20146 Hamburg Germany

Department of Life and Environmental Sciences University of Cagliari Monserrato Italy

Drake University College of Pharmacy and Health Sciences Des Moines IA USA

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo Nam 2 CZ 16610 Prague 6 Czech Republic

KU Leuven Rega Institute for Medical Research Laboratory of Virology and Chemotherapy B 3000 Leuven Belgium

Vir Biotechnology Inc San Francisco CA USA

Viral Special Pathogens Branch Division of High Consequence Pathogens and Pathology Centers for Disease Control and Prevention Atlanta GA USA

Zobrazit více v PubMed

Acosta-Hoyos A.J., Scott W.A. The role of nucleotide excision by reverse transcriptase in HIV drug resistance. Viruses. 2010;2:372–394. PubMed PMC

Alexandre F.R., Rahali R., Rahali H., Guillon S., Convard T., Fillgrove K., Lai M.T., Meillon J.C., Xu M., Small J., Dousson C.B., Raheem I.T. Synthesis and antiviral evaluation of carbocyclic nucleoside analogs of nucleoside reverse transcriptase translocation inhibitor MK-8591 (4'-Ethynyl-2-fluoro-2'-deoxyadenosine) J. Med. Chem. 2018;61:9218–9228. PubMed

Althouse B.M., Vasilakis N., Sall A.A., Diallo M., Weaver S.C., Hanley K.A. Potential for Zika virus to establish a sylvatic transmission cycle in the Americas. PLoS Neglected Trop. Dis. 2016;10 PubMed PMC

Andrei G., Carter K., Janeba Z., Sampath A., Schang L.M., Tarbet E.B., Vere Hodge R.A., Bray M., Este J.A. Highlights of the 30th international conference on antiviral research. Antivir. Res. 2017;145:184–196. PubMed PMC

Andrei G., Gammon D.B., Fiten P., De Clercq E., Opdenakker G., Snoeck R., Evans D.H. Cidofovir resistance in vaccinia virus is linked to diminished virulence in mice. J. Virol. 2006;80:9391–9401. PubMed PMC

Andrei G., Topalis D., De Schutter T., Snoeck R. Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia. Antivir. Res. 2015;114:21–46. PubMed

Backer J.A., Vrancken R., Neyts J., Goris N. The potential of antiviral agents to control classical swine fever: a modelling study. Antivir. Res. 2013;99:245–250. PubMed

Bar-On Y., Gruell H., Schoofs T., Pai J.A., Nogueira L., Butler A.L., Millard K., Lehmann C., Suarez I., Oliveira T.Y., Karagounis T., Cohen Y.Z., Wyen C., Scholten S., Handl L., Belblidia S., Dizon J.P., Vehreschild J.J., Witmer-Pack M., Shimeliovich I., Jain K., Fiddike K., Seaton K.E., Yates N.L., Horowitz J., Gulick R.M., Pfeifer N., Tomaras G.D., Seaman M.S., Fatkenheuer G., Caskey M., Klein F., Nussenzweig M.C. Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat. Med. 2018;24:1701–1707. PubMed PMC

Barrett S.E., Teller R.S., Forster S.P., Li L., Mackey M.A., Skomski D., Yang Z., Fillgrove K.L., Doto G.J., Wood S.L., Lebron J., Grobler J.A., Sanchez R.I., Liu Z., Lu B., Niu T., Sun L., Gindy M.E. Extended-duration MK-8591-eluting implant as a candidate for HIV treatment and prevention. Antimicrob. Agents Chemother. 2018;62 PubMed PMC

Berg T., Simon K.G., Mauss S., Schott E., Heyne R., Klass D.M., Eisenbach C., Welzel T.M., Zachoval R., Felten G., Schulze-Zur-Wiesch J., Cornberg M., Op den Brouw M.L., Jump B., Reiser H., Gallo L., Warger T., Petersen J., investigators F.C.s. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study. J. Hepatol. 2017;67:918–924. PubMed

Bray M., Andrei G., Ballana E., Carter K., Durantel D., Gentry B., Janeba Z., Moffat J., Oomen C.J., Tarbet B., Riveira-Munoz E., Este J.A., International Society for Antiviral R. Meeting report: 31(st) international conference on antiviral research. Antivir. Res. 2018;158:88–102. PubMed PMC

Britt W.J., Prichard M.N. New therapies for human cytomegalovirus infections. Antivir. Res. 2018;159:153–174. PubMed

Caskey M., Klein F., Nussenzweig M.C. Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic. Nat. Med. 2019;25:547–553. PubMed PMC

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. PubMed PMC

Dash P.K., Kaminski R., Bella R., Su H., Mathews S., Ahooyi T.M., Chen C., Mancuso P., Sariyer R., Ferrante P., Donadoni M., Robinson J.A., Sillman B., Lin Z., Hilaire J.R., Banoub M., Elango M., Gautam N., Mosley R.L., Poluektova L.Y., McMillan J., Bade A.N., Gorantla S., Sariyer I.K., Burdo T.H., Young W.-B., Amini S., Gordon J., Jacobson J.M., Edagwa B., Khalili K., Gendelman H.E. Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice. Nat. Commun. 2019 (in press) PubMed PMC

El-Serag H.B., Rudolph K.L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576. PubMed

Gammon D.B., Evans D.H. The 3'-to-5' exonuclease activity of vaccinia virus DNA polymerase is essential and plays a role in promoting virus genetic recombination. J. Virol. 2009;83:4236–4250. PubMed PMC

Gordon S.C., Lamerato L.E., Rupp L.B., Li J., Holmberg S.D., Moorman A.C., Spradling P.R., Teshale E.H., Vijayadeva V., Boscarino J.A., Henkle E.M., Oja-Tebbe N., Lu M., Investigators C.H. Antiviral therapy for chronic hepatitis B virus infection and development of hepatocellular carcinoma in a US population. Clin. Gastroenterol. Hepatol. 2014;12:885–893. PubMed PMC

Guo F., Zhao Q., Sheraz M., Cheng J., Qi Y., Su Q., Cuconati A., Wei L., Du Y., Li W., Chang J., Guo J.T. HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways. PLoS Pathog. 2017;13 PubMed PMC

Hegde S.T., Salje H., Sazzad H.M.S., Hossain M.J., Rahman M., Daszak P., Klena J.D., Nichol S.T., Luby S.P., Gurley E.S. Using healthcare-seeking behaviour to estimate the number of Nipah outbreaks missed by hospital-based surveillance in Bangladesh. Int. J. Epidemiol. 2019 PubMed PMC

Hoy S.M. Tecovirimat: first global approval. Drugs. 2018;78:1377–1382. PubMed

Julien O., Beadle J.R., Magee W.C., Chatterjee S., Hostetler K.Y., Evans D.H., Sykes B.D. Solution structure of a DNA duplex containing the potent anti-poxvirus agent cidofovir. J. Am. Chem. Soc. 2011;133:2264–2274. PubMed PMC

Kimberlin D.W., Acosta E.P., Sanchez P.J., Sood S., Agrawal V., Homans J., Jacobs R.F., Lang D., Romero J.R., Griffin J., Cloud G.A., Lakeman F.D., Whitley R.J., National Institute of A., Infectious Diseases Collaborative Antiviral Study G. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J. Infect. Dis. 2008;197:836–845. PubMed

Kimberlin D.W., Jester P.M., Sanchez P.J., Ahmed A., Arav-Boger R., Michaels M.G., Ashouri N., Englund J.A., Estrada B., Jacobs R.F., Romero J.R., Sood S.K., Whitworth M.S., Abzug M.J., Caserta M.T., Fowler S., Lujan-Zilbermann J., Storch G.A., DeBiasi R.L., Han J.Y., Palmer A., Weiner L.B., Bocchini J.A., Dennehy P.H., Finn A., Griffiths P.D., Luck S., Gutierrez K., Halasa N., Homans J., Shane A.L., Sharland M., Simonsen K., Vanchiere J.A., Woods C.R., Sabo D.L., Aban I., Kuo H., James S.H., Prichard M.N., Griffin J., Giles D., Acosta E.P., Whitley R.J., National Institute of A., Infectious Diseases Collaborative Antiviral Study G. Valganciclovir for symptomatic congenital cytomegalovirus disease. N. Engl. J. Med. 2015;372:933–943. PubMed PMC

Kimberlin D.W., Lin C.Y., Sanchez P.J., Demmler G.J., Dankner W., Shelton M., Jacobs R.F., Vaudry W., Pass R.F., Kiell J.M., Soong S.J., Whitley R.J., National Institute of A., Infectious Diseases Collaborative Antiviral Study G. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J. Pediatr. 2003;143:16–25. PubMed

Lim S.P. Dengue drug discovery: progress, challenges and outlook. Antivir. Res. 2019;163:156–178. PubMed

Magee W.C., Aldern K.A., Hostetler K.Y., Evans D.H. Cidofovir and (S)-9-[3-hydroxy-(2-phosphonomethoxy)propyl]adenine are highly effective inhibitors of vaccinia virus DNA polymerase when incorporated into the template strand. Antimicrob. Agents Chemother. 2008;52:586–597. PubMed PMC

Magee W.C., Hostetler K.Y., Evans D.H. Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate. Antimicrob. Agents Chemother. 2005;49:3153–3162. PubMed PMC

Magee W.C., Valiaeva N., Beadle J.R., Richman D.D., Hostetler K.Y., Evans D.H. Inhibition of HIV-1 by octadecyloxyethyl esters of (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] nucleosides and evaluation of their mechanism of action. Antimicrob. Agents Chemother. 2011;55:5063–5072. PubMed PMC

Markowitz M., Gettie A., St Bernard L., Andrews C.D., Mohri H., Horowitz A., Grasperge B.F., Blanchard J.L., Niu T., Sun L., Fillgrove K., Hazuda D.J., Grobler J.A. Title: once-weekly oral dosing of MK-8591 protects male rhesus macaques from intrarectal SHIV109CP3 challenge. J. Infect. Dis. 2019 PubMed

Matthews R.P., Schürmann D., Rudd D.J., Levine V., Fox-Bosetti S., Zhang S., Robberechts M., Huser A., Hazuda D.J., Iwamoto M. 9th International AIDS Society Conference on HIV Science. 2007. Single doses as low as 0.5 mg of the novel NRTTI MK-8591 suppress HIV for at least seven days.

Mendoza P., Gruell H., Nogueira L., Pai J.A., Butler A.L., Millard K., Lehmann C., Suarez I., Oliveira T.Y., Lorenzi J.C.C., Cohen Y.Z., Wyen C., Kummerle T., Karagounis T., Lu C.L., Handl L., Unson-O'Brien C., Patel R., Ruping C., Schlotz M., Witmer-Pack M., Shimeliovich I., Kremer G., Thomas E., Seaton K.E., Horowitz J., West A.P., Jr., Bjorkman P.J., Tomaras G.D., Gulick R.M., Pfeifer N., Fatkenheuer G., Seaman M.S., Klein F., Caskey M., Nussenzweig M.C. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018;561:479–484. PubMed PMC

Michailidis E., Huber A.D., Ryan E.M., Ong Y.T., Leslie M.D., Matzek K.B., Singh K., Marchand B., Hagedorn A.N., Kirby K.A., Rohan L.C., Kodama E.N., Mitsuya H., Parniak M.A., Sarafianos S.G. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanisms. J. Biol. Chem. 2014;289:24533–24548. PubMed PMC

Mouquet H. Antibody B cell responses in HIV-1 infection. Trends Immunol. 2014;35:549–561. PubMed

Nikolay B., Salje H., Hossain M.J., Khan A., Sazzad H.M.S., Rahman M., Daszak P., Stroher U., Pulliam J.R.C., Kilpatrick A.M., Nichol S.T., Klena J.D., Sultana S., Afroj S., Luby S.P., Cauchemez S., Gurley E.S. Transmission of Nipah virus - 14 Years of investigations in Bangladesh. N. Engl. J. Med. 2019;380:1804–1814. PubMed PMC

Plaszczyca A., Scaturro P., Neufeldt C.J., Cortese M., Cerikan B., Ferla S., Brancale A., Pichlmair A., Bartenschlager R. A novel interaction between dengue virus nonstructural protein 1 and the NS4A-2K-4B precursor is required for viral RNA replication but not for formation of the membranous replication organelle. PLoS Pathog. 2019;15 PubMed PMC

Seley-Radtke K.L., Yates M.K. The evolution of nucleoside analogue antivirals: a review for chemists and non-chemists. Part 1: early structural modifications to the nucleoside scaffold. Antivir. Res. 2018;154:66–86. PubMed PMC

Sillman B., Bade A.N., Dash P.K., Bhargavan B., Kocher T., Mathews S., Su H., Kanmogne G.D., Poluektova L.Y., Gorantla S., McMillan J., Gautam N., Alnouti Y., Edagwa B., Gendelman H.E. Creation of a long-acting nanoformulated dolutegravir. Nat. Commun. 2018;9:443. PubMed PMC

Sinclair J., Reeves M. The intimate relationship between human cytomegalovirus and the dendritic cell lineage. Front. Microbiol. 2014;5:389. PubMed PMC

Tarbouriech N., Ducournau C., Hutin S., Mas P.J., Man P., Forest E., Hart D.J., Peyrefitte C.N., Burmeister W.P., Iseni F. The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding. Nat. Commun. 2017;8:1455. PubMed PMC

Tsetsarkin K.A., Vanlandingham D.L., McGee C.E., Higgs S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog. 2007;3 PubMed PMC

Vanchiere J.A., Ruiz J.C., Brady A.G., Kuehl T.J., Williams L.E., Baze W.B., Wilkerson G.K., Nehete P.N., McClure G.B., Rogers D.L., Rossi S.L., Azar S.R., Roundy C.M., Weaver S.C., Vasilakis N., Simmons J.H., Abee C.R. Experimental Zika virus infection of neotropical primates. Am. J. Trop. Med. Hyg. 2018;98:173–177. PubMed PMC

Vere Hodge R.A. Meeting report: 26th international conference on antiviral research. Antivir. Res. 2013;100:276–285. PubMed PMC

Vere Hodge R.A. Meeting report: 27th International conference on antiviral research, in Raleigh, NC, USA. Antivir. Res. 2014;111:143–153. PubMed PMC

Vere Hodge R.A. Meeting report: 28th international conference on antiviral research in rome, Italy. Antivir. Res. 2015;123:172–187. PubMed PMC

Vere Hodge R.A. Meeting report: 29th international conference on antiviral research in La Jolla, CA, USA. Antivir. Res. 2017;137:23–40. PubMed PMC

Vrancken R., Haegeman A., Dewulf J., Paeshuyse J., Puerstinger G., Tignon M., Le Potier M.F., Neyts J., Koenen F. The reduction of CSFV transmission to untreated pigs by the pestivirus inhibitor BPIP: a proof of concept. Vet. Microbiol. 2009;139:365–368. PubMed

Vrancken R., Haegeman A., Paeshuyse J., Puerstinger G., Rozenski J., Wright M., Tignon M., Le Potier M.F., Neyts J., Koenen F. Proof of concept for the reduction of classical swine fever infection in pigs by a novel viral polymerase inhibitor. J. Gen. Virol. 2009;90:1335–1342. PubMed

Willer D.O., Mann M.J., Zhang W., Evans D.H. Vaccinia virus DNA polymerase promotes DNA pairing and strand-transfer reactions. Virology. 1999;257:511–523. PubMed

Yang G., Pevear D.C., Davies M.H., Collett M.S., Bailey T., Rippen S., Barone L., Burns C., Rhodes G., Tohan S., Huggins J.W., Baker R.O., Buller R.L., Touchette E., Waller K., Schriewer J., Neyts J., DeClercq E., Jones K., Hruby D., Jordan R. An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge. J. Virol. 2005;79:13139–13149. PubMed PMC

Yates M.K., Seley-Radtke K.L. The evolution of antiviral nucleoside analogues: a review for chemists and non-chemists. Part II: complex modifications to the nucleoside scaffold. Antivir. Res. 2019;162:5–21. PubMed PMC

Zhou T., Block T., Liu F., Kondratowicz A.S., Sun L., Rawat S., Branson J., Guo F., Steuer H.M., Liang H., Bailey L., Moore C., Wang X., Cuconatti A., Gao M., Lee A.C.H., Harasym T., Chiu T., Gotchev D., Dorsey B., Rijnbrand R., Sofia M.J. HBsAg mRNA degradation induced by a dihydroquinolizinone compound depends on the HBV posttranscriptional regulatory element. Antivir. Res. 2018;149:191–201. PubMed

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