Viral infections have recently emerged not only as a health threat to people but rapidly became the cause of universal fatality on a large scale. Nanomaterials comprising functionalized nanoparticles (NPs) and quantum dots and nanotechnology-associated innovative detection methods, vaccine design, and nanodrug production have shown immense promise for interfacing with pathogenic viruses and restricting their entrance into cells. These viruses have been scrutinized using rapid diagnostic detection and therapeutic interventional options against the caused infections including vaccine development for prevention and control. Coronaviruses, namely SARS-CoV, MERS-CoV, and SARS-CoV-2, have endangered human life, and the COVID-19 (caused by SARS-CoV-2) outbreak has become a perilous challenge to public health globally with huge accompanying morbidity rates. Thus, it is imperative to expedite the drug and vaccine development efforts that would help mitigate this pandemic. In this regard, smart and innovative nano-based technologies and approaches encompassing applications of green nanomedicine, bio-inspired methods, multifunctional bioengineered nanomaterials, and biomimetic drug delivery systems/carriers can help resolve the critical issues regarding detection, prevention, and treatment of viral infections. This perspective review expounds recent nanoscience advancements for the detection and treatment of viral infections with focus on coronaviruses and encompasses nano-based formulations and delivery platforms, nanovaccines, and promising methods for clinical diagnosis, especially regarding SARS-CoV-2.

Department of Chemistry Faculty of Science University of Qom Qom 37185 359 Iran

Faculty of Pharmacy and Pharmaceutical Sciences Isfahan University of Medical Sciences Isfahan 81746 73461 Iran

Radiology Department School of Medicine Isfahan University of Medical Sciences Isfahan 81746 73461 Iran

Regional Centre of Advanced Technologies and Materials Palacký University in Olomouc Šlechtitelů 27 783 71 CZ 779 00 Olomouc Czech Republic

Zobrazit více v PubMed

Kahn R.E., Ma W., Richt J.A. Influenza Pathogenesis and Control-Volume I. Springer; Berlin, Germany: 2014. Swine and influenza: A challenge to one health research; pp. 205–218. PubMed

Qasim M., Lim D.-J., Park H., Na D. Nanotechnology for diagnosis and treatment of infectious diseases. J. Nanosci. Nanotechnol. 2014;14:7374–7387. doi: 10.1166/jnn.2014.9578. PubMed DOI

Wejse C., Patsche C.B., Kühle A., Bamba F.J.V., Mendes M.S., Lemvik G., Gomes V.F., Rudolf F. Impact of HIV-1, HIV-2, and HIV-1+ 2 dual infection on the outcome of tuberculosis. Int. J. Infect. Dis. 2015;32:128–134. doi: 10.1016/j.ijid.2014.12.015. PubMed DOI

Braden C.R., Dowell S.F., Jernigan D.B., Hughes J.M. Progress in global surveillance and response capacity 10 years after severe acute respiratory syndrome. Emerg. Infect. Dis. 2013;19:864. doi: 10.3201/eid1906.130192. PubMed DOI PMC

World Health Organization . World Health Statistics 2016: Monitoring Health for the SDGs Sustainable Development Goals. World Health Organization; Geneva, Switzerland: 2016.

Kutter J.S., Spronken M.I., Fraaij P.L., Fouchier R.A.M., Herfst S. Transmission routes of respiratory viruses among humans. Curr. Opin. Virol. 2018;28:142–151. doi: 10.1016/j.coviro.2018.01.001. PubMed DOI PMC

Pavia A.T. Viral infections of the lower respiratory tract: Old viruses, new viruses, and the role of diagnosis. Clin. Infect. Dis. 2011;52:S284–S289. doi: 10.1093/cid/cir043. PubMed DOI PMC

Walker T.A., Khurana S., Tilden S.J. Viral respiratory infections. Pediatric Clin. North Am. 1994;41:1365–1381. doi: 10.1016/S0031-3955(16)38876-9. PubMed DOI

Cojocaru F.-D., Botezat D., Gardikiotis I., Uritu C.-M., Dodi G., Trandafir L., Rezus C., Rezus E., Tamba B.-I., Mihai C.-T. Nanomaterials designed for antiviral drug delivery transport across biological barriers. Pharmaceutics. 2020;12:171. doi: 10.3390/pharmaceutics12020171. PubMed DOI PMC

Wong S.S.Y., Yuen K.-Y. The management of coronavirus infections with particular reference to SARS. J. Antimicrob. Chemother. 2008;62:437–441. doi: 10.1093/jac/dkn243. PubMed DOI PMC

Principi N., Piralla A., Zampiero A., Bianchini S., Umbrello G., Scala A., Bosis S., Fossali E., Baldanti F., Esposito S. Bocavirus infection in otherwise healthy children with respiratory disease. PLoS ONE. 2015:10. doi: 10.1371/journal.pone.0135640. PubMed DOI PMC

Gorbalenya A.E., Baker S.C., Baric R.S., de Groot R.J., Drosten C., Gulyaeva A.A., Haagmans B.I., Iauber C., Ieontovich A.M., Neuman B.W., et al. The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020:5. doi: 10.1038/s41564-41020-40695-z. PubMed DOI PMC

Branche A.R., Falsey A.R. Parainfluenza virus infection. Semin. Resp. Crit. Care Med. 2016:538–554. doi: 10.1055/s-0036-1584798. PubMed DOI PMC

Mazur N.I., Higgins D., Nunes M.C., Melero J.A., Langedijk A.C., Horsley N., Buchholz U.J., Openshaw P.J., McLellan J.S., Englund J.A. The respiratory syncytial virus vaccine landscape: Lessons from the graveyard and promising candidates. Lancet Infect. Dis. 2018;18:e295–e311. doi: 10.1016/S1473-3099(18)30292-5. PubMed DOI

Lu M.-P., Ma L.-Y., Zheng Q., Dong L.-L., Chen Z.-M. Clinical characteristics of adenovirus associated lower respiratory tract infection in children. World J. Pediatrics. 2013;9:346–349. doi: 10.1007/s12519-013-0431-3. PubMed DOI

Munster V.J., Koopmans M., van Doremalen N., van Riel D., de Wit E. A novel coronavirus emerging in China—key questions for impact assessment. New Engl. J. Med. 2020;382:692–694. doi: 10.1056/NEJMp2000929. PubMed DOI

Sportelli M.C., Izzi M., Kukushkina E.A., Hossain S.I., Picca R.A., Ditaranto N., Cioffi N. Can Nanotechnology and Materials Science Help the Fight against SARS-CoV-2? Nanomaterials. 2020;10:802. doi: 10.3390/nano10040802. PubMed DOI PMC

Hayden F. Developing new antiviral agents for influenza treatment: What does the future hold? Clin. Infect. Dis. 2009;48:S3–S13. doi: 10.1086/591851. PubMed DOI

Little S.J., Holte S., Routy J.-P., Daar E.S., Markowitz M., Collier A.C., Koup R.A., Mellors J.W., Connick E., Conway B. Antiretroviral-drug resistance among patients recently infected with HIV. N. Engl. J. Med. 2002;347:385–394. doi: 10.1056/NEJMoa013552. PubMed DOI

Maseko S.B., Natarajan S., Sharma V., Bhattacharyya N., Govender T., Sayed Y., Maguire G.E.M., Lin J., Kruger H.G. Purification and characterization of naturally occurring HIV-1 (South African subtype C) protease mutants from inclusion bodies. Protein Expr. Purif. 2016;122:90–96. doi: 10.1016/j.pep.2016.02.013. PubMed DOI

Parboosing R., Maguire G.E.M., Govender P., Kruger H.G. Nanotechnology and the treatment of HIV infection. Viruses. 2012;4:488–520. doi: 10.3390/v4040488. PubMed DOI PMC

Nasrollahzadeh M., Sajadi S.M., Sajjadi M., Issaabadi Z. Interface Science and Technology. Volume 28. Elsevier; Amsterdam, The Netherlands: 2019. An Introduction to Nanotechnology; pp. 1–27.

Moghimi S.M., Hunter A.C., Murray J.C. Nanomedicine: Current status and future prospects. FASEB J. 2005;19:311–330. doi: 10.1096/fj.04-2747rev. PubMed DOI

Chen Y.-C., Cheng H.-F., Yang Y.-C., Yeh M.-K. Nanotechnologies applied in biomedical vaccines. Micro Nanotechn. Biotech. 2016 doi: 10.5772/63453d. DOI

Kingsley J.D., Dou H., Morehead J., Rabinow B., Gendelman H.E., Destache C.J. Nanotechnology: A focus on nanoparticles as a drug delivery system. J. Neuroimmune Pharmacol. 2006;1:340–350. doi: 10.1007/s11481-006-9032-4. PubMed DOI

Poeschla E.M. Integrase, LEDGF/p75 and HIV replication. Cell. Mol. Life Sci. 2008;65:1403–1424. doi: 10.1007/s00018-008-7540-5. PubMed DOI PMC

Adesina S.K., Akala E.O. Nanotechnology approaches for the delivery of exogenous siRNA for HIV therapy. Mol. Pharm. 2015;12:4175–4187. doi: 10.1021/acs.molpharmaceut.5b00335. PubMed DOI PMC

Duan L., Yan Y., Liu J., Wang B., Li P., Hu Q., Chen W. Target delivery of small interfering RNAs with vitamin E-coupled nanoparticles for treating hepatitis C. Sci. Rep. 2016;6:24867. doi: 10.1038/srep24867. PubMed DOI PMC

Yang X.X., Li C.M., Huang C.Z. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection. Nanoscale. 2016;8:3040–3048. doi: 10.1039/C5NR07918G. PubMed DOI

Li Y., Lin Z., Zhao M., Guo M., Xu T., Wang C., Xia H., Zhu B. Reversal of H1N1 influenza virus-induced apoptosis by silver nanoparticles functionalized with amantadine. RSC Adv. 2016;6:89679–89686. doi: 10.1039/C6RA18493F. DOI

Li Y., Lin Z., Guo M., Zhao M., Xia Y., Wang C., Xu T., Zhu B. Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium nanoparticles with amantadine through ROS-mediated AKT signaling pathways. Int. J. Nanomed. 2018;13:2005. doi: 10.2147/IJN.S155994. PubMed DOI PMC

Li Y., Lin Z., Guo M., Xia Y., Zhao M., Wang C., Xu T., Chen T., Zhu B. Inhibitory activity of selenium nanoparticles functionalized with oseltamivir on H1N1 influenza virus. Int. J. Nanomed. 2017;12:5733. doi: 10.2147/IJN.S140939. PubMed DOI PMC

Hu C.-M.J., Chen Y.-T., Fang Z.-S., Chang W.-S., Chen H.-W. Antiviral efficacy of nanoparticulate vacuolar ATPase inhibitors against influenza virus infection. Int. J. Nanomed. 2018;13:8579. doi: 10.2147/IJN.S185806. PubMed DOI PMC

Yang X., Shah S.J., Wang Z., Agrahari V., Pal D., Mitra A.K. Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir. Drug Deliv. 2016;23:2399–2409. doi: 10.3109/10717544.2014.996833. PubMed DOI

Yadavalli T., Ames J., Agelidis A., Suryawanshi R., Jaishankar D., Hopkins J., Thakkar N., Koujah L., Shukla D. Drug-encapsulated carbon (DECON): A novel platform for enhanced drug delivery. Sci. Adv. 2019;5:eaax0780. doi: 10.1126/sciadv.aax0780. PubMed DOI PMC

Öztürk A.A., Kırımlıoğlu G.Y. Preparation and in vitro of characterization lamivudine loaded nanoparticles prepared by acid or ester terminated PLGA for effective oral antiretroviral therapy. J. Res. Pharm. 2019;23:897–913.

Venkatesh D.N., Baskaran M., Karri V.V.S.R., Mannemala S.S., Radhakrishna K., Goti S. Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect. Saudi Pharm. J. 2015;23:667–674. doi: 10.1016/j.jsps.2015.02.021. PubMed DOI PMC

Shah L.K., Amiji M.M. Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for HIV/AIDS. Pharm. Res. 2006;23:2638–2645. doi: 10.1007/s11095-006-9101-7. PubMed DOI

Tang X., Liang Y., Liu X., Zhou S., Liu L., Zhang F., Xie C., Cai S., Wei J., Zhu Y. PLGA-PEG nanoparticles coated with anti-CD45RO and loaded with HDAC plus protease inhibitors activate latent HIV and inhibit viral spread. Nanoscale Res. Lett. 2015;10:1–8. doi: 10.1186/s11671-015-1112-z. PubMed DOI PMC

Sankar V., Keerthi M.L., Parmar N. Formation and In-vitro Evaluation of Zidovudine-Lamivudine Nanoparticles. Ind. J. Pharma. Educ. Res. 2012;46:192–196.

Fiandra L., Colombo M., Mazzucchelli S., Truffi M., Santini B., Allevi R., Nebuloni M., Capetti A., Rizzardini G., Prosperi D. Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice. Nanomed. Nanotechnol. Biol. Med. 2015;11:1387–1397. doi: 10.1016/j.nano.2015.03.009. PubMed DOI

Donalisio M., Leone F., Civra A., Spagnolo R., Ozer O., Lembo D., Cavalli R. Acyclovir-loaded chitosan nanospheres from nano-emulsion templating for the topical treatment of herpesviruses infections. Pharmaceutics. 2018;10:46. doi: 10.3390/pharmaceutics10020046. PubMed DOI PMC

Lauster D., Glanz M., Bardua M., Ludwig K., Hellmund M., Hoffmann U., Hamann A., Böttcher C., Haag R., Hackenberger C.P.R. Multivalent Peptide–Nanoparticle Conjugates for Influenza-Virus Inhibition. Angew. Chem. Int. Ed. 2017;56:5931–5936. doi: 10.1002/anie.201702005. PubMed DOI PMC

Freeling J.P., Koehn J., Shu C., Sun J., Ho R.J.Y. Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates. AIDS Res. Hum. Retrovir. 2015;31:107–114. doi: 10.1089/aid.2014.0210. PubMed DOI PMC

Duan J., Freeling J.P., Koehn J., Shu C., Ho R.J.Y. Evaluation of atazanavir and darunavir interactions with lipids for developing pH-responsive anti-HIV drug combination nanoparticles. J. Pharm. Sci. 2014;103:2520–2529. doi: 10.1002/jps.24046. PubMed DOI PMC

Raskin M.M., Schlachet I., Sosnik A. Mucoadhesive nanogels by ionotropic crosslinking of chitosan-g-oligo (NiPAam) polymeric micelles as novel drug nanocarriers. Nanomedicine. 2016;11:217–233. doi: 10.2217/nnm.15.191. PubMed DOI

Ahmed S.R., Nagy E., Neethirajan S. Self-assembled star-shaped chiroplasmonic gold nanoparticles for ultrasensitive chiro-immunosensor of viruses. RSC Adv. 2017;7:40849–40857. doi: 10.1039/C7RA07175B. DOI

Chen Y.-N., Hsueh Y.-H., Hsieh C.-T., Tzou D.-Y., Chang P.-L. Antiviral activity of graphene-silver nanocomposites against non-enveloped and enveloped viruses. Int. J. Env. Res. Public Health. 2016;13:430. doi: 10.3390/ijerph13040430. PubMed DOI PMC

Layqah L.A., Eissa S. An electrochemical immunosensor for the corona virus associated with the Middle East respiratory syndrome using an array of gold nanoparticle-modified carbon electrodes. Mikrochim. Acta. 2019;186:224. doi: 10.1007/s00604-019-3345-5. PubMed DOI PMC

Sekimukai H., Iwata-Yoshikawa N., Fukushi S., Tani H., Kataoka M., Suzuki T., Hasegawa H., Niikura K., Arai K., Nagata N. Gold nanoparticle-adjuvanted S protein induces a strong antigen-specific IgG response against severe acute respiratory syndrome-related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs. Microbiol. Immunol. 2020;64:33–51. doi: 10.1111/1348-0421.12754. PubMed DOI PMC

Ting D., Dong N., Fang L., Lu J., Bi J., Xiao S., Han H. Multisite Inhibitors for Enteric Coronavirus: Antiviral Cationic Carbon Dots Based on Curcumin. ACS Appl. Nano Mater. 2018;1:5451–5459. doi: 10.1021/acsanm.8b00779. PubMed DOI

Du T., Liang J., Dong N., Lu J., Fu Y., Fang L., Xiao S., Han H. Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through Blockage of Viral RNA Synthesis and Budding. ACS Appl. Mater. Interfaces. 2018;10:4369–4378. doi: 10.1021/acsami.7b13811. PubMed DOI

Ahmed S.R., Kang S.W., Oh S., Lee J., Neethirajan S. Chiral zirconium quantum dots: A new class of nanocrystals for optical detection of coronavirus. Heliyon. 2018;4:e00766. doi: 10.1016/j.heliyon.2018.e00766. PubMed DOI PMC

Mo Y., Fisher D. Review of Treatment Modalities Of Middle Repsiratorey Syndroms. J. Antimicrob. Chemother. 2016;71:3340–3350. doi: 10.1093/jac/dkw338. PubMed DOI PMC

Uyeki T.M., Erlandson K.J., Korch G., O’Hara M., Wathen M., Hu-Primmer J., Hojvat S., Stemmy E.J., Donabedian A. Evelopment of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus. Emerg. Infect. Dis. 2016;22:1–6. doi: 10.3201/eid2207.160022. PubMed DOI PMC

Zumla A., Chan J.F.W., Azhar E.I., Hui D.S.C., Yuen K.-Y. Coronavirus-Drug Discovery and Therapeutic Options. Nat. Rev. 2016;15:327–347. PubMed PMC

Łoczechin A., Séron K., Barras A., Giovanelli E., Belouzard S., Chen Y.T., Metzler-Nolte N., Boukherroub R., Dubuisson J., Szunerits S. Functional Carbon Quantum Dots as Medical Countermeasures to Human Coronavirus. ACS Appl. Mater. Interfaces. 2019;11:42964–42974. doi: 10.1021/acsami.9b15032. PubMed DOI PMC

Du L., Yang Y., Zhou Y., Lu L., Li F., Jiang S. ERS-Cov Spike Protein: A Key Target for Antivirals. Exp. Opin. Ther. Targets. 2017;21:131–143. doi: 10.1080/14728222.2017.1271415. PubMed DOI PMC

Lu L., Liu Q., Zhu Y., Chan K.-H., Qin L., Li Y., Wang Q., Chan J.F.W., Du L., Yu F., et al. Sructures-Based Discovery Of Middle East Repiratory Syndrome Coronavirus Fusion Inhibitor. Nat. Commun. 2014;5:1–15. PubMed PMC

Szunerits S., Barras A., Khanal M., Pagneux Q., Boukherroub R. Nanostructures for the Inhibition of Viral Infections. Molecules. 2015;20:14051–14081. doi: 10.3390/molecules200814051. PubMed DOI PMC

Huang X., Li M., Xu Y., Zhang J., Meng X., An X., Sun L., Guo L., Shan X., Ge J., et al. Novel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus. ACS Appl. Mater. Interfaces. 2019;11:19799–19807. doi: 10.1021/acsami.9b04240. PubMed DOI

Zhou Y., Jiang X., Tong T., Fang L., Wu Y., Liang J., Xiao S. High antiviral activity of mercaptoethane sulfonate functionalized Te/BSA nanostars against arterivirus and coronavirus. RSC Adv. 2020;10:14161–14169. doi: 10.1039/D0RA01387K. PubMed DOI PMC

Walsh J.H., Yalow R.S., Berson S.A. Radioimmunoassay of Australia antigen. VoxSanguinis. 1970;19:217–224. PubMed

Bosch A. In: Diagnostic Virology Protocols. John R., Stephenson A.W., editors. Volume 2. Springer; Berlin/Heidelberg, Germany: 1999. p. 56.

Zehbe I., Hacker G.W., Su H., Hauser-Kronberger C., Hainfeld J.F., Tubbs R. Sensitive in situ hybridization with catalyzed reporter deposition, streptavidin-Nanogold, and silver acetate autometallography: Detection of single-copy human papillomavirus. Am. J. Pathol. 1997;150:1553. PubMed PMC

Wang X., Liu L.-H., Ramstroem O., Yan M. Engineering nanomaterial surfaces for biomedical applications. Exp. Biol. Med. 2009;234:1128–1139. doi: 10.3181/0904-MR-134. PubMed DOI PMC

Alivisatos P. The use of nanocrystals in biological detection. Nat. Biotechnol. 2004;22:47–52. doi: 10.1038/nbt927. PubMed DOI

Rosi N.L., Mirkin C.A. Nanostructures in biodiagnostics. Chem. Rev. 2005;105:1547–1562. doi: 10.1021/cr030067f. PubMed DOI

Draz M.S., Shafiee H. Applications of gold nanoparticles in virus detection. Theranostics. 2018;8:1985. doi: 10.7150/thno.23856. PubMed DOI PMC

Qiu G., Gai Z., Tao Y., Schmitt J., Kullak-Ublick G.A., Wang J. Dual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 Detection. ACS Nano. 2020 doi: 10.1021/acsnano.0c02439. PubMed DOI

Seo G., Lee G., Kim M.J., Baek S.H., Choi M., Ku K.B., Lee C.S., Jun S., Park D., Kim H.G., et al. Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor. ACS Nano. 2020 doi: 10.1021/acsnano.0c02823. PubMed DOI

Rauch S., Jasny E., Schmidt K.E., Petsch B. New vaccine technologies to combat outbreak situations. Front. Immunol. 2018;9:1963. doi: 10.3389/fimmu.2018.01963. PubMed DOI PMC

Callaway E. The race for coronavirus vaccines: A graphical guide. Nature. 2020;580:576–577. doi: 10.1038/d41586-020-01221-y. PubMed DOI

Shang W., Yang Y., Rao Y., Rao X. The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines. NPJ Vaccin. 2020:5. doi: 10.1038/s41541-020-0170-0. PubMed DOI PMC

Amanat F., Krammer F. SARS-CoV-2 Vaccines: Status Report. Immunity. 2020;52:583–589. doi: 10.1016/j.immuni.2020.03.007. PubMed DOI PMC

Thanh Le T., Andreadakis Z., Kumar A., Gómez Román R., Tollefsen S., Saville M., Mayhew S. The COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. 2020;19:305–306. doi: 10.1038/d41573-020-00073-5. PubMed DOI

Naiman B.M., Alt D., Bolin C.A., Zuerner R., Baldwin C.L. Protective killed Leptospira borgpetersenii vaccine induces potent Th1 immunity comprising responses by CD4 and γδ T lymphocytes. Infect. Immun. 2001;69:7550–7558. doi: 10.1128/IAI.69.12.7550-7558.2001. PubMed DOI PMC

Saha A., Chowdhury M.I., Nazim M., Alam M.M., Ahmed T., Hossain M.B., Hore S.K., Sultana G.N.N., Svennerholm A.-M., Qadri F. Vaccine specific immune response to an inactivated oral cholera vaccine and EPI vaccines in a high and low arsenic area in Bangladeshi children. Vaccine. 2013;31:647–652. doi: 10.1016/j.vaccine.2012.11.049. PubMed DOI

Scallan C.D., Tingley D.W., Lindbloom J.D., Toomey J.S., Tucker S.N. An adenovirus-based vaccine with a double-stranded RNA adjuvant protects mice and ferrets against H5N1 avian influenza in oral delivery models. Clin. Vaccine Immunol. 2013;20:85–94. doi: 10.1128/CVI.00552-12. PubMed DOI PMC

Epstein J.E., Tewari K., Lyke K.E., Sim B.K.L., Billingsley P.F., Laurens M.B., Gunasekera A., Chakravarty S., James E.R., Sedegah M. Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity. Science. 2011;334:475–480. doi: 10.1126/science.1211548. PubMed DOI

Norton E.B., Lawson L.B., Mahdi Z., Freytag L.C., Clements J.D. The A subunit of Escherichia coli heat-labile enterotoxin functions as a mucosal adjuvant and promotes IgG2a, IgA, and Th17 responses to vaccine antigens. Infect. Immun. 2012;80:2426–2435. doi: 10.1128/IAI.00181-12. PubMed DOI PMC

Tevi-Benissan M.C., Moturi E., Anya B.-P.M., Aschalew T., Dicky A.B., Nyembo P.A., Mbulu L.K., Okeibunor J., Mihigo R., Zawaira F. Contribution of polio eradication initiative to effective new vaccine introduction in Africa, 2010–2015. Vaccine. 2016;34:5193–5198. doi: 10.1016/j.vaccine.2016.05.063. PubMed DOI

Nuismer S.L., Althouse B.M., May R., Bull J.J., Stromberg S.P., Antia R. Eradicating infectious disease using weakly transmissible vaccines. Proc. Biol. Sci. 2016;283:20161903. doi: 10.1098/rspb.2016.1903. PubMed DOI PMC

Staroverov S.A., Vidyasheva I.V., Gabalov K.P., Vasilenko O.A., Laskavyi V.N., Dykman L.A. Immunostimulatory effect of gold nanoparticles conjugated with transmissible gastroenteritis virus. Bull. Exp. Biol. Med. 2011;151:436. doi: 10.1007/s10517-011-1350-8. PubMed DOI PMC

Kim Y.S., Son A., Kim J., Kwon S.B., Kim M.H., Kim P., Kim J., Byun Y.H., Sung J., Lee J., et al. Chaperna-Mediated Assembly of Ferritin-Based Middle East Respiratory Syndrome-Coronavirus Nanoparticles. Front. Immunol. 2018;9:1093. doi: 10.3389/fimmu.2018.01093. PubMed DOI PMC

Lin L.C.W., Huang C.Y., Yao B.Y., Lin J.C., Agrawal A., Algaissi A., Peng B.H., Liu Y.H., Huang P.H., Juang R.H., et al. Viromimetic STING agonist-loaded hollow polymeric nanoparticles for safe and effective vaccination against Middle East respiratory syndrome coronavirus. Adv. Funct. Mater. 2019;29:1807616. doi: 10.1002/adfm.201807616. PubMed DOI PMC

Jung S.Y., Kang K.W., Lee E.Y., Seo D.W., Kim H.L., Kim H., Kwon T., Park H.L., Kim H., Lee S.M., et al. Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East Respiratory syndrome coronavirus. Vaccine. 2018;36:3468–3476. doi: 10.1016/j.vaccine.2018.04.082. PubMed DOI PMC

Ball J.M., Graham D.Y., Opekun A.R., Gilger M.A., Guerrero R.A., Estes M.K. Recombinant Norwalk virus–like particles given orally to volunteers: Phase I study. Gastroenterology. 1999;117:40–48. doi: 10.1016/S0016-5085(99)70548-2. PubMed DOI

Geldmacher A., Skrastina D., Borisova G., Petrovskis I., Krüger D.H., Pumpens P., Ulrich R. A hantavirus nucleocapsid protein segment exposed on hepatitis B virus core particles is highly immunogenic in mice when applied without adjuvants or in the presence of pre-existing anti-core antibodies. Vaccine. 2005;23:3973–3983. doi: 10.1016/j.vaccine.2005.02.025. PubMed DOI

Xu L., Liu Y., Chen Z., Li W., Liu Y., Wang L., Liu Y., Wu X., Ji Y., Zhao Y. Surface-engineered gold nanorods: Promising DNA vaccine adjuvant for HIV-1 treatment. Nano Lett. 2012;12:2003–2012. doi: 10.1021/nl300027p. PubMed DOI

Tao W., Gill H.S. M2e-immobilized gold nanoparticles as influenza A vaccine: Role of soluble M2e and longevity of protection. Vaccine. 2015;33:2307–2315. doi: 10.1016/j.vaccine.2015.03.063. PubMed DOI PMC

Chen Y.-S., Hung Y.-C., Lin W.-H., Huang G.S. Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide. Nanotechnology. 2010;21:195101. doi: 10.1088/0957-4484/21/19/195101. PubMed DOI

Tao W., Hurst B.L., Shakya A.K., Uddin M.J., Ingrole R.S.J., Hernandez-Sanabria M., Arya R.P., Bimler L., Paust S., Tarbet E.B. Consensus M2e peptide conjugated to gold nanoparticles confers protection against H1N1, H3N2 and H5N1 influenza A viruses. Antivir. Res. 2017;141:62–72. doi: 10.1016/j.antiviral.2017.01.021. PubMed DOI PMC

Lugade A.A., Bharali D.J., Pradhan V., Elkin G., Mousa S.A., Thanavala Y. Single low-dose un-adjuvanted HBsAg nanoparticle vaccine elicits robust, durable immunity. Nanomed. Nanotechnol. Biol. Med. 2013;9:923–934. doi: 10.1016/j.nano.2013.03.008. PubMed DOI

Schreiber H.A., Prechl J., Jiang H., Zozulya A., Fabry Z., Denes F., Sandor M. Using carbon magnetic nanoparticles to target, track, and manipulate dendritic cells. J. Immunol. Method. 2010;356:47–59. doi: 10.1016/j.jim.2010.02.009. PubMed DOI PMC

Zhao K., Chen G., Shi X.-M., Gao T.-T., Li W., Zhao Y., Zhang F.-Q., Wu J., Cui X., Wang Y.-F. Preparation and efficacy of a live newcastle disease virus vaccine encapsulated in chitosan nanoparticles. PLoS ONE. 2012:7. doi: 10.1371/journal.pone.0053314. PubMed DOI PMC

Jesus S., Soares E., Costa J., Borchard G., Borges O. Immune response elicited by an intranasally delivered HBsAg low-dose adsorbed to poly-ε-caprolactone based nanoparticles. Int. J. Pharm. 2016;504:59–69. doi: 10.1016/j.ijpharm.2016.03.013. PubMed DOI

Okamoto S., Matsuura M., Akagi T., Akashi M., Tanimoto T., Ishikawa T., Takahashi M., Yamanishi K., Mori Y. Poly (γ-glutamic acid) nano-particles combined with mucosal influenza virus hemagglutinin vaccine protects against influenza virus infection in mice. Vaccine. 2009;27:5896–5905. doi: 10.1016/j.vaccine.2009.07.037. PubMed DOI

Bright R.A., Carter D.M., Daniluk S., Toapanta F.R., Ahmad A., Gavrilov V., Massare M., Pushko P., Mytle N., Rowe T. Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin. Vaccine. 2007;25:3871–3878. doi: 10.1016/j.vaccine.2007.01.106. PubMed DOI

Parez N., Fourgeux C., Mohamed A., Dubuquoy C., Pillot M., Dehee A., Charpilienne A., Poncet D., Schwartz-Cornil I., Garbarg-Chenon A. Rectal immunization with rotavirus virus-like particles induces systemic and mucosal humoral immune responses and protects mice against rotavirus infection. J. Virol. 2006;80:1752–1761. doi: 10.1128/JVI.80.4.1752-1761.2006. PubMed DOI PMC

Pimentel T.A.P.F., Yan Z., Jeffers S.A., Holmes K.V., Hodges R.S., Burkhard P. Peptide nanoparticles as novel immunogens: Design and analysis of a prototypic severe acute respiratory syndrome vaccine. Chem. Biol. Drug Des. 2009;73:53–61. doi: 10.1111/j.1747-0285.2008.00746.x. PubMed DOI PMC

Borges O., Cordeiro-da-Silva A., Tavares J., Santarém N., de Sousa A., Borchard G., Junginger H.E. Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles. Eur. J. Pharm. Biopharm. 2008;69:405–416. doi: 10.1016/j.ejpb.2008.01.019. PubMed DOI

Thomas C., Rawat A., Hope-Weeks L., Ahsan F. Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine responses to hepatitis B vaccine. Mol. Pharm. 2011;8:405–415. doi: 10.1021/mp100255c. PubMed DOI

Raghuvanshi R.S., Katare Y.K., Lalwani K., Ali M.M., Singh O., Panda A.K. Improved immune response from biodegradable polymer particles entrapping tetanus toxoid by use of different immunization protocol and adjuvants. Int. J. Pharm. 2002;245:109–121. doi: 10.1016/S0378-5173(02)00342-3. PubMed DOI

Mansoor F., Earley B., Cassidy J.P., Markey B., Doherty S., Welsh M.D. Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves. BMC Vet. Res. 2015;11:220. doi: 10.1186/s12917-015-0481-y. PubMed DOI PMC

McGill J.L., Kelly S.M., Kumar P., Speckhart S., Haughney S.L., Henningson J., Narasimhan B., Sacco R.E. Efficacy of mucosal polyanhydride nanovaccine against respiratory syncytial virus infection in the neonatal calf. Sci. Rep. 2018;8:1–15. doi: 10.1038/s41598-018-21292-2. PubMed DOI PMC

Francica J.R., Lynn G.M., Laga R., Joyce M.G., Ruckwardt T.J., Morabito K.M., Chen M., Chaudhuri R., Zhang B., Sastry M. Thermoresponsive polymer nanoparticles co-deliver RSV F trimers with a TLR-7/8 adjuvant. Bioconjugate Chem. 2016;27:2372–2385. doi: 10.1021/acs.bioconjchem.6b00370. PubMed DOI

Lynn G.M., Laga R., Darrah P.A., Ishizuka A.S., Balaci A.J., Dulcey A.E., Pechar M., Pola R., Gerner M.Y., Yamamoto A. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nat. Biotechnol. 2015;33:1201. doi: 10.1038/nbt.3371. PubMed DOI PMC

Tai W., Roberts L., Seryshev A., Gubatan J.M., Bland C.S., Zabriskie R., Kulkarni S., Soong L., Mbawuike I., Gilbert B. Multistrain influenza protection induced by a nanoparticulate mucosal immunotherapeutic. Mucosal Immunol. 2011;4:197–207. doi: 10.1038/mi.2010.50. PubMed DOI

Zhao M., Li M., Zhang Z., Gong T., Sun X. Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA. Drug Deliv. 2016;23:2596–2607. doi: 10.3109/10717544.2015.1038856. PubMed DOI

Fredriksen B.N., Grip J. PLGA/PLA micro-and nanoparticle formulations serve as antigen depots and induce elevated humoral responses after immunization of Atlantic salmon (Salmo salar L.) Vaccine. 2012;30:656–667. doi: 10.1016/j.vaccine.2011.10.105. PubMed DOI

Kumar A., Ma H., Zhang X., Huang K., Jin S., Liu J., Wei T., Cao W., Zou G., Liang X.-J. Gold nanoparticles functionalized with therapeutic and targeted peptides for cancer treatment. Biomaterials. 2012;33:1180–1189. doi: 10.1016/j.biomaterials.2011.10.058. PubMed DOI

McNeil S.E. Characterization of Nanoparticles Intended for Drug Delivery. Springer; Berlin, Germany: 2011. Unique benefits of nanotechnology to drug delivery and diagnostics; pp. 3–8. PubMed

Chiappetta D.A., Facorro G., de Celis E.R., Sosnik A. Synergistic encapsulation of the anti-HIV agent efavirenz within mixed poloxamine/poloxamer polymeric micelles. Nanomed. Nanotechnol. Biol. Med. 2011;7:624–637. doi: 10.1016/j.nano.2011.01.017. PubMed DOI

Santos-Martinez M.J., Rahme K., Corbalan J.J., Faulkner C., Holmes J.D., Tajber L., Medina C., Radomski M.W. Pegylation increases platelet biocompatibility of gold nanoparticles. J. Biomed. Nanotechnol. 2014;10:1004–1015. doi: 10.1166/jbn.2014.1813. PubMed DOI

Alexis F., Pridgen E., Molnar L.K., Farokhzad O.C. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 2008;5:505–515. doi: 10.1021/mp800051m. PubMed DOI PMC

Apostolopoulos V., Thalhammer T., Tzakos A.G., Stojanovska L. Targeting antigens to dendritic cell receptors for vaccine development. J. Drug Deliv. 2013;2013 doi: 10.1155/2013/869718. PubMed DOI PMC

Raghuwanshi D., Mishra V., Suresh M.R., Kaur K. A simple approach for enhanced immune response using engineered dendritic cell targeted nanoparticles. Vaccine. 2012;30:7292–7299. doi: 10.1016/j.vaccine.2012.09.036. PubMed DOI

Misumi S., Masuyama M., Takamune N., Nakayama D., Mitsumata R., Matsumoto H., Urata N., Takahashi Y., Muneoka A., Sukamoto T. Targeted delivery of immunogen to primate m cells with tetragalloyl lysine dendrimer. J. Immunol. 2009;182:6061–6070. doi: 10.4049/jimmunol.0802928. PubMed DOI

Lepenies B., Lee J., Sonkaria S. Targeting C-type lectin receptors with multivalent carbohydrate ligands. Adv. Drug Deliv. Rev. 2013;65:1271–1281. doi: 10.1016/j.addr.2013.05.007. PubMed DOI

Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.-L., Abiona O., Graham B.S., McLellan J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260–1263. doi: 10.1126/science.abb2507. PubMed DOI PMC

Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;180:1–12. doi: 10.1016/j.cell.2020.02.058. PubMed DOI PMC

Coleman C.M., Liu Y.V., Mu H., Taylor J.K., Massare M., Flyer D.C., Smith G.E., Frieman M.B. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine. 2014;32:3169–3174. doi: 10.1016/j.vaccine.2014.04.016. PubMed DOI PMC

Liu Y.V., Massare M.J., Barnard D.L., Kort T., Nathan M., Wang L., Smith G. Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV. Vaccine. 2011;29:6606–6613. doi: 10.1016/j.vaccine.2011.06.111. PubMed DOI PMC

Coleman C.M., Venkataraman T., Liu Y.V., Glenn G.M., Smith G.E., Flyer D.C., Frieman M.B. MERS-CoV spike nanoparticles protect mice from MERS-CoV infection. Vaccine. 2017;35:1586–1589. doi: 10.1016/j.vaccine.2017.02.012. PubMed DOI PMC

Kato T., Takami Y., Deo V.K., Park E.Y. Preparation of virus-like particle mimetic nanovesicles displaying the S protein of Middle East respiratory syndrome coronavirus using insect cells. J. Biotechnol. 2019;306:177–184. doi: 10.1016/j.jbiotec.2019.10.007. PubMed DOI PMC

Sanchez-Guzman D., Le Guen P., Villeret B., Sola N., Le Borgne R., Guyard A., Kemmel A., Crestani B., Sallenave J.M., Garcia-Verdugo I. Silver nanoparticle-adjuvanted vaccine protects against lethal influenza infection through inducing BALT and IgA-mediated mucosal immunity. Biomaterials. 2019;217:119308. doi: 10.1016/j.biomaterials.2019.119308. PubMed DOI

Ye S., Shao K., Li Z., Guo N., Zuo Y., Li Q., Lu Z., Chen L., He Q., Han H. Antiviral Activity of Graphene Oxide: How Sharp Edged Structure and Charge Matter. ACS Appl. Mater. Interfaces. 2015;7:21571–21579. doi: 10.1021/acsami.5b06876. PubMed DOI

Du T., Lu J., Liu L., Dong N., Fang L., Xiao S., Han H. Antiviral Activity of Graphene Oxide–Silver Nanocomposites by Preventing Viral Entry and Activation of the Antiviral Innate Immune Response. ACS Appl. Bio Mater. 2018;1:1286–1293. doi: 10.1021/acsabm.8b00154. PubMed DOI

Sanhai W.R., Sakamoto J.H., Canady R., Ferrari M. Seven challenges for nanomedicine. Nat. Nanotechnol. 2008;3:242. doi: 10.1038/nnano.2008.114. PubMed DOI

Duncan R., Gaspar R. Nanomedicine (s) under the microscope. Mol. Pharm. 2011;8:2101–2141. doi: 10.1021/mp200394t. PubMed DOI

Ferrari M. Cancer nanotechnology: Opportunities and challenges. Nat. Rev. Cancer. 2005;5:161–171. doi: 10.1038/nrc1566. PubMed DOI

De Oliveira M.P., Garcion E., Venisse N., Benoît J.-P., Couet W., Olivier J.-C. Tissue distribution of indinavir administered as solid lipid nanocapsule formulation in mdr1a (+/+) and mdr1a (−/−) CF-1 mice. Pharm. Res. 2005;22:1898–1905. doi: 10.1007/s11095-005-7147-6. PubMed DOI

Caron J., Reddy L.H., Lepêtre-Mouelhi S., Wack S., Clayette P., Rogez-Kreuz C., Yousfi R., Couvreur P., Desmaële D. Squalenoyl nucleoside monophosphate nanoassemblies: New prodrug strategy for the delivery of nucleotide analogues. Bioorg. Med. Chem. Lett. 2010;20:2761–2764. doi: 10.1016/j.bmcl.2010.03.070. PubMed DOI

Sanvicens N., Marco M.P. Multifunctional nanoparticles–properties and prospects for their use in human medicine. Trends Biotechnol. 2008;26:425–433. doi: 10.1016/j.tibtech.2008.04.005. PubMed DOI

Gagliardi M. Biomimetic and bioinspired nanoparticles for targeted drug delivery. Ther. Deliv. 2017;8:289–299. doi: 10.4155/tde-2017-0013. PubMed DOI

Lara H.H., Ayala-Nuñez N.V., Ixtepan-Turrent L., Rodriguez-Padilla C. Mode of antiviral action of silver nanoparticles against HIV-1. J. Nanobiotechn. 2010;8:1. doi: 10.1186/1477-3155-8-1. PubMed DOI PMC

Mallipeddi R., Rohan L.C. Progress in antiretroviral drug delivery using nanotechnology. Int. J. Nanomed. 2010;5:533. PubMed PMC

Petros R.A., DeSimone J.M. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 2010;9:615–627. doi: 10.1038/nrd2591. PubMed DOI

Maurer P., Jennings G.T., Willers J., Rohner F., Lindman Y., Roubicek K., Renner W.A., Müller P., Bachmann M.F. A therapeutic vaccine for nicotine dependence: Preclinical efficacy, and Phase I safety and immunogenicity. Eur. J. Immunol. 2005;35:2031–2040. doi: 10.1002/eji.200526285. PubMed DOI

Roldao A., Mellado M.C.M., Castilho L.R., Carrondo M.J.T., Alves P.M. Virus-like particles in vaccine development. Expert Rev. Vaccin. 2010;9:1149–1176. doi: 10.1586/erv.10.115. PubMed DOI

Greenwood B. The contribution of vaccination to global health: Past, present and future. R. Soc. 2014;369:20130433. doi: 10.1098/rstb.2013.0433. PubMed DOI PMC

Peek L.J., Middaugh C.R., Berkland C. Nanotechnology in vaccine delivery. Adv. Drug Deliv. Rev. 2008;60:915–928. doi: 10.1016/j.addr.2007.05.017. PubMed DOI PMC

Nandedkar T.D. Nanovaccines: Recent developments in vaccination. J. Biosci. 2009;34:995–1003. doi: 10.1007/s12038-009-0114-3. PubMed DOI

Zhao L., Seth A., Wibowo N., Zhao C.-X., Mitter N., Yu C., Middelberg A.P.J. Nanoparticle vaccines. Vaccine. 2014;32:327–337. doi: 10.1016/j.vaccine.2013.11.069. PubMed DOI

Kerry R.G., Malik S., Redda Y.T., Sahoo S., Patra J.K., Majhi S. Nano-based approach to combat emerging viral (NIPAH virus) infection. Nanomed. Nanotechnol. Biol. Med. 2019;18:196–220. doi: 10.1016/j.nano.2019.03.004. PubMed DOI PMC

Shaligram S., Campbell A. Toxicity of copper salts is dependent on solubility profile and cell type tested. Toxicol. Vitr. 2013;27:844–851. doi: 10.1016/j.tiv.2012.12.026. PubMed DOI

Zhu S., Li J., Huang A.-G., Huang J.-Q., Huang Y.-Q., Wang G.-X. Anti-betanodavirus activity of isoprinosine and improved efficacy using carbon nanotubes based drug delivery system. Aquaculture. 2019;512:734377. doi: 10.1016/j.aquaculture.2019.734377. DOI

Singh L., Kruger H.G., Maguire G.E.M., Govender T., Parboosing R. The role of nanotechnology in the treatment of viral infections. Adv. Infect. Dis. 2017;4:105–131. doi: 10.1177/2049936117713593. PubMed DOI PMC

Dormont F., Brusini R., Cailleau C., Reynaud F., Peramo A., Gendron A., Mougin J., Gaudin F., Varna M., Couvreur P. Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation. Sci. Adv. 2020:eaaz5466. doi: 10.1126/sciadv.aaz5466. PubMed DOI PMC

Nanosponges: An overlooked promising strategy to combat SARS-CoV-2

Quantum dots against SARS-CoV-2: diagnostic and therapeutic potentials