COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics

Kuldeep Dhama, Khan Sharun, Ruchi Tiwari, Maryam Dadar, Yashpal Singh Malik, Karam Pal Singh, Wanpen Chaicumpa, Kuldeep Dhama, Khan Sharun, Ruchi Tiwari, Maryam Dadar, Yashpal Singh Malik, Karam Pal Singh, Wanpen Chaicumpa

Abstract

The novel coronavirus infection (COVID-19 or Coronavirus disease 2019) that emerged from Wuhan, Hubei province of China has spread to many countries worldwide. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS in the past decades. However, to date, no licensed antiviral treatment or vaccine exists for MERS and SARS. Most of the efforts for developing CoV vaccines and drugs target the spike glycoprotein or S protein, the major inducer of neutralizing antibodies. Although a few candidates have shown efficacy in in vitro studies, not many have progressed to randomized animal or human trials, hence may have limited use to counter COVID-19 infection. This article highlights ongoing advances in designing vaccines and therapeutics to counter COVID-19 while also focusing on such experiences and advances as made with earlier SARS- and MERS-CoVs, which together could enable efforts to halt this emerging virus infection.

Keywords: COVID-19; Emerging coronavirus; drugs; therapeutics; vaccines.

References

    1. Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, Haagmans BL, Lauber C, Leontovich AM, Neuman BW, et al. Severe acute respiratory syndrome-related coronavirus: the species and its viruses–a statement of the coronavirus study group. BioRxiv. 2020. 2020.02.07.937862. doi:10.1101/2020.02.07.937862.
    1. Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020. doi:10.5582/bst.2020.01020.
    1. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):222. doi:10.1038/s41467-019-13940-6.
    1. Pillaiyar T, Meenakshisundaram S, Manickam M. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discov Today. 2020. S1359-6446(20)30041–6. doi:10.1016/j.drudis.2020.01.015.
    1. Graham RL, Donaldson EF, Baric RS. A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol. 2013;11(12):836–48. doi:10.1038/nrmicro3143.
    1. Munjal A, Khandia R, Dhama K, Sachan S, Karthik K, Tiwari R, Malik YS, Kumar D, Singh RK, Iqbal HMN, et al. Advances in developing therapies to combat Zika virus: current knowledge and future perspectives. Front Microbiol. 2017;8:1469. doi:10.3389/fmicb.2017.01469.
    1. Dhama K, Karthik K, Khandia R, Chakraborty S, Munjal A, Latheef SK, Kumar D, Ramakrishnan MA, Malik YS, Singh R, et al. Advances in designing and developing vaccines, drugs, and therapies to counter Ebola virus. Front Immunol. 2018;9:1803. doi:10.3389/fimmu.2018.01803.
    1. Singh RK, Dhama K, Chakraborty S, Tiwari R, Natesan S, Khandia R, Munjal A, Vora KS, Latheef SK, Karthik K, et al. Nipah virus: epidemiology, pathology, immunobiology and advances in diagnosis, vaccine designing and control strategies - a comprehensive review. Vet Q. 2019;39(1):26–55. doi:10.1080/01652176.2019.1580827.
    1. Yang ZY, Kong WP, Huang Y, Roberts A, Murphy BR, Subbarao K, Nabel GJ. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature. 2004;428(6982):561–64. doi:10.1038/nature02463.
    1. Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, Kao RY, Poon LL, Wong CL, Guan Y, et al., HKU/UCH SARS Study Group . Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59(3):252–56. doi:10.1136/thorax.2003.012658.
    1. Kumar V, Jung Y-S, Liang P-H. Anti-SARS coronavirus agents: a patent review (2008–present). Expert Opin Ther Pat. 2013;23(10):1337–48. doi:10.1517/13543776.2013.823159.
    1. Li E, Yan F, Huang P, Chi H, Xu S, Li G, Liu C, Feng N, Wang H, Zhao YY. Characterization of the immune response of MERS-CoV vaccine candidates derived from two different vectors in mice. Viruses. 2020a;12(1):pii: E125. doi:10.3390/v12010125.
    1. Cyranoski D. This scientist hopes to test coronavirus drugs on animals in locked-down Wuhan. Nature. 2020;577(7792):607. doi:10.1038/d41586-020-00190-6.
    1. Malik YS, Sircar S, Bhat S, Sharun K, Dhama K, Dadar M, Tiwari R, Chaicumpa W. Emerging novel coronavirus (2019-nCoV) - Current scenario, evolutionary perspective based on genome analysis and recent developments. Vet Q. 2020:1–12. doi:10.1080/01652176.2020.1727993.
    1. Zaher NH, Mostafa MI, Altaher AY. Design, synthesis and molecular docking of novel triazole derivatives as potential CoV helicase inhibitors. Acta Pharm. 2020;70(2):145–59. doi:10.2478/acph-2020-0024.
    1. WHO . Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected; 2020. [accessed 2020 February15].
    1. Li H, Wang YM, Xu JY, Cao B. Potential antiviral therapeutics for 2019 novel coronavirus. Zhonghua Jie He He Hu Xi ZaZhi. 2020b;43:E002. Chinese. doi:10.3760/cma.j..1001-0939.2020.0002.
    1. Jiang S, He Y, Liu S. SARS vaccine development. Emerg Infect Dis. 2005;11(7):1016–20. doi:10.3201/1107.050219.
    1. Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV–a target for vaccine and therapeutic development. Nat Rev Microbiol. 2009;7(3):226–36. doi:10.1038/nrmicro2090.
    1. Ji W, Wang W, Zhao X, Zai J, Li X. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. J Med Virol. 2020. doi:10.1002/jmv.25682.
    1. Widjaja I, Wang C, van Haperen R, Gutiérrez-Álvarez J, van Dieren B, Okba NMA, Raj VS, Li W, Fernandez-Delgado R, Grosveld F, et al. Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein. Emerging Microbes Infect. 2019;8(1):516–30. doi:10.1080/22221751.2019.1597644.
    1. Chen R, Fu J, Hu J, Li C, Zhao Y, Qu H, Wen X, Cao S, Wen Y, Wu R. Identification of the immunodominant neutralizing regions in the spike glycoprotein of porcine deltacoronavirus. Virus Res. 2020;276:197834. doi:10.1016/j.virusres.2019.197834.
    1. Buchholz UJ, Bukreyev A, Yang L, Lamirande EW, Murphy BR, Subbarao K, Collins PL. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc Natl Acad Sci U S A. 2004;101(26):9804–09. doi:10.1073/pnas.0403492101.
    1. Kim MH, Kim HJ, Chang J. Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length spike protein of Middle East respiratory syndrome coronavirus. PLoS One. 2019;14(7):e0220196. doi:10.1371/journal.pone.0220196.
    1. Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, Gao GF. T-cell immunity of SARS-CoV: implications for vaccine development against MERS-CoV. Antiviral Res. 2017;137:82–92. doi:10.1016/j.antiviral.2016.11.006.
    1. Jiang S, Du L, Shi Z. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerging Microbes Infect. 2020;9(1):275–77. doi:10.1080/22221751.2020.1723441.
    1. Yu F, Du L, Ojcius DM, Pan C, Jiang S. Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes Infect. 2020. S1286-4579(20)30025–3. doi:10.1016/j.micinf.2020.01.003.
    1. Liu W, Morse JS, Lalonde T, Xu S. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. Chembiochem. 2020. doi:10.1002/cbic.202000047.
    1. Veljkovic V, Vergara-Alert J, Segalés J, Paessler S. Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target. F1000Research. 2020;9(52):52. doi:10.12688/f1000research.22149.1.
    1. Baruah V, Bose S. Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV. J Med Virol. 2020. doi:10.1002/jmv.25698.
    1. Shi J, Zhang J, Li S, Sun J, Teng Y, Wu M, Li J, Li Y, Hu N, Wang H, et al. Epitope-based vaccine target screening against highly pathogenic MERS-CoV: an in silico approach applied to emerging infectious diseases. PLoS One. 2015;10(12):e0144475. doi:10.1371/journal.pone.0144475.
    1. Xie Q, He X, Yang F, Liu X, Li Y, Liu Y, Yang Z, Yu J, Zhang B, Zhao W. Analysis of the genome sequence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus. IEEE/ACM Trans Comput Biol Bioinform. 2018;15(4):1344–50. doi:10.1109/TCBB.2017.2702588.
    1. Bijlenga G. Proposal for vaccination against SARS coronavirus using avian infectious bronchitis virus strain H from The Netherlands. J Infect. 2005;51(3):263–65. doi:10.1016/j.jinf.2005.04.010.
    1. Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systemic review. J Med Virol. 2020. doi:10.1002/jmv.25707.
    1. NIAID . Developing therapeutics and vaccines for coronaviruses; 2020. [accessed 2020 February15].
    1. CEPI . CEPI to fund three programmes to develop vaccines against the novel coronavirus, nCoV-2019; 2020. [accessed 2020 February15].
    1. Moderna . Moderna announces funding award from CEPI to accelerate development of messenger RNA (mRNA) vaccine against novel coronavirus; 2020. [accessed 2020 February15].
    1. Goo J, Jeong Y, Park Y-S, Yang E, Jung D-I, Rho S, Park U, Sung H, Park P-G, Choi JA. Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein. Virus Res. 2020;278:197863. doi:10.1016/j.virusres.2020.197863.
    1. Zeng LP, Ge XY, Peng C, Tai W, Jiang S, Du L, Shi ZL. Cross-neutralization of SARS coronavirus-specific antibodies against bat SARS-like coronaviruses. Sci China Life Sci. 2017;60(12):1399–402. doi:10.1007/s11427-017-9189-3.
    1. Cohen J. New coronavirus threat galvanizes scientists. Science. 2020;367(6477):492–93. doi:10.1126/science.367.6477.492.
    1. Seesuay W, Jittavisutthikul S, Sae-Lim N, Sookrung N, Sakolvaree Y, Chaicumpa W. Human transbodies that interfere with the functions of Ebola virus VP35 protein in genome replication and transcription and innate immune antagonism. Emerging Microbes Infect. 2018;7(1):41. doi:10.1038/s41426-018-0031-3.
    1. Gretebeck LM, Subbarao K. Animal models for SARS and MERS coronaviruses. Curr Opin Virol. 2015;13:123–29. doi:10.1016/j.coviro.2015.06.009.
    1. Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS. Recent advances in the vaccine development against Middle East respiratory syndrome-coronavirus. Front Microbiol. 2019;10:1781. doi:10.3389/fmicb.2019.01781.
    1. Martina BE, Haagmans BL, Kuiken T, Fouchier RA, Rimmelzwaan GF, Van Amerongen G, Peiris JS, Lim W, Osterhaus AD. Virology: SARS virus infection of cats and ferrets. Nature. 2003;425(6961):915. doi:10.1038/425915a.
    1. Roberts A, Wood J, Subbarao K, Ferguson M, Wood D, Cherian T. Animal models and antibody assays for evaluating candidate SARS vaccines: summary of a technical meeting 25-26 August 2005, London, UK. Vaccine. 2006;24(49–50):7056–65. doi:10.1016/j.vaccine.2006.07.009.
    1. Lamirande EW, DeDiego ML, Roberts A, Jackson JP, Alvarez E, Sheahan T, Shieh WJ, Zaki SR, Baric R, Enjuanes L, et al. A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters. J Virol. 2008;82(15):7721–24. doi:10.1128/JVI.00304-08.
    1. Roberts A, Lamirande EW, Vogel L, Jackson JP, Paddock CD, Guarner J, Zaki SR, Sheahan T, Baric R, Subbarao K. Animal models and vaccines for SARS-CoV infection. Virus Res. 2008;133(1):20–32. doi:10.1016/j.virusres.2007.03.025.
    1. Zhao J, Li K, Wohlford-Lenane C, Agnihothram SS, Fett C, Zhao J, Gale MJ Jr, Baric RS, Enjuanes L, Gallagher T, et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A. 2014;111(13):4970–75. doi:10.1073/pnas.1323279111.
    1. Du L, Tai W, Zhou Y, Jiang S. Vaccines for the prevention against the threat of MERS-CoV. Expert Rev Vaccines. 2016;15(9):1123–34. doi:10.1586/14760584.2016.1167603.
    1. Enjuanes L, Zuñiga S, Castaño-rodriguez C, Gutierrez-Alvarez J, Canton J, Sola I. Molecular basis of coronavirus virulence and vaccine development. Adv Virus Res. 2016;96:245–86. doi:10.1016/bs.aivir.2016.08.003.
    1. Yang XH, Deng W, Tong Z, Liu YX, Zhang LF, Zhu H, Gao H, Huang L, Liu YL, Ma CM, et al. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comp Med. 2007;57:450–59.
    1. Munster VJ, de Wit E, Feldmann H. Pneumonia from human coronavirus in a macaque model. N Engl J Med. 2013;368(16):1560–62. doi:10.1056/NEJMc1215691.
    1. Falzarano D, de Wit E, Feldmann F, Rasmussen AL, Okumura A, Peng X, Thomas MJ, van Doremalen N, Haddock E, Nagy L, et al. Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog. 2014;10(8):e1004250. doi:10.1371/journal.ppat.1004250.
    1. Menachery VD, Gralinski LE, Mitchell HD, Dinnon KH 3rd, Leist SR, Yount BL Jr, McAnarney ET, Graham RL, Waters KM, Baric RS. Combination attenuation offers strategy for live attenuated coronavirus vaccines. J Virol. 2018;92(17):e00710–18. doi:10.1128/JVI.00710-18.
    1. Zhou Y, Jiang S, Du L. Prospects for a MERS-CoV spike vaccine. Expert Rev Vaccines. 2018;17(8):677–86. doi:10.1080/14760584.2018.1506702.
    1. Cockrell AS, Yount BL, Scobey T, Jensen K, Douglas M, Beall A, Tang XC, Marasco WA, Heise MT, Baric RS. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome. Nat Microbiol. 2016;2:16226. doi:10.1038/nmicrobiol.2016.226.
    1. Leist SR, Cockrell AS. Genetically engineering a susceptible mouse model for MERS-CoV-induced acute respiratory distress syndrome. Methods Mol Biol. 2020;2099:137–59. doi:10.1007/978-1-0716-0211-9_12.
    1. Eckerle I, Corman VM, Müller MA, Lenk M, Ulrich RG, Drosten C. Replicative capacity of MERS coronavirus in livestock cell lines. Emerg Infect Dis. 2014;20(2):276–79. doi:10.3201/eid2002.131182.
    1. Hofmann H, Hattermann K, Marzi A, Gramberg T, Geier M, Krumbiegel M, Kuate S, Uberla K, Niedrig M, Pöhlmann S. S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients. J Virol. 2004;78(12):6134–42. doi:10.1128/JVI.78.12.6134-6142.2004.
    1. Milewska A, Nowak P, Owczarek K, Szczepanski A, Zarebski M, Hoang A, Berniak K, Wojarski J, Zeglen S, Baster Z, et al. Entry of human coronavirus NL63 into the cell. J Virol. 2018;92(3):e01933–17. doi:10.1128/JVI.01933-17.
    1. Moore MJ, Dorfman T, Li W, Wong SK, Li Y, Kuhn JH, Coderre J, Vasilieva N, Han Z, Greenough TC, et al. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. J Virol. 2004;78(19):10628–35. doi:10.1128/JVI.78.19.10628-10635.2004.
    1. Fukushi S, Mizutani T, Saijo M, Kurane I, Taguchi F, Tashiro M, Morikawa S. Evaluation of a novel vesicular stomatitis virus pseudotype-based assay for detection of neutralizing antibody responses to SARS-CoV. J Med Virol. 2006;78(12):1509–12. doi:10.1002/jmv.20732.
    1. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020a. doi:10.1038/s41422-020-0282-0.
    1. Kilianski A, Baker SC. Cell-based antiviral screening against coronaviruses: developing virus-specific and broad-spectrum inhibitors. Antiviral Res. 2014;101:105–12. doi:10.1016/j.antiviral.2013.11.004.
    1. Xu J, Jia W, Wang P, Zhang S, Shi X, Wang X, Zhang L. Antibodies and vaccines against Middle East respiratory syndrome coronavirus. Emerg Infect Dis. 2019;8(1):841–56. doi:10.1080/22221751.2019.1624482.
    1. Qu D, Zheng B, Yao X, Guan Y, Yuan ZH, Zhong NS, Lu LW, Xie JP, Wen YM. Intranasal immunization with inactivated SARS-CoV (SARS-associated coronavirus) induced local and serum antibodies in mice. Vaccine. 2005;23(7):924–31. doi:10.1016/j.vaccine.2004.07.031.
    1. Lee JS, Poo H, Han DP, Hong SP, Kim K, Cho MW, Kim E, Sung MH, Kim CJ. Mucosal immunization with surface-displayed severe acute respiratory syndrome coronavirus spike protein on Lactobacillus casei induces neutralizing antibodies in mice. J Virol. 2006;80(8):4079–87. doi:10.1128/JVI.80.8.4079-4087.2006.
    1. Adedeji AO, Severson W, Jonsson C, Singh K, Weiss SR, Sarafianos SG. Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms. J Virol. 2013;87(14):8017–28. doi:10.1128/JVI.00998-13.
    1. Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, Brining D, Bushmaker T, Martellaro C, Baseler L, et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med. 2013;19(10):1313–17. doi:10.1038/nm.3362.
    1. Lu L, Liu Q, Du L, Jiang S. Middle East respiratory syndrome coronavirus (MERS-CoV): challenges in identifying its source and controlling its spread. Microbes Infect. 2013;15(8–9):625–29. doi:10.1016/j.micinf.2013.06.003.
    1. Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020:1–8. doi:10.1038/d41573-020-00016-0.
    1. Sun ML, Yang JM, Sun YP, Su GH. Inhibitors of RAS might be a good choice for the therapy of COVID-19 pneumonia. ZhonghuaJie He Hu Xi ZaZhi. 2020;43:E014. Chinese. doi:10.3760/cma.j..1001-0939.2020.0014.
    1. Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15(5):327–47. doi:10.1038/nrd.2015.37.
    1. Chan JF, Yao Y, Yeung ML, Deng W, Bao L, Jia L, Li F, Xiao C, Gao H, Yu P, et al. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J Infect Dis. 2015;212(12):1904–13. doi:10.1093/infdis/jiv392.
    1. Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, Kojan S, Al Jeraisy M, Deeb AM, Assiri AM, et al.; And the MIRACLE trial group . Treatment of Middle East respiratory syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials. 2018;19(1):81. doi:10.1186/s13063-017-2427-0.
    1. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020b;395:470–73. S0140-6736(20)30185-9. doi:10.1016/S0140-6736(20)30185-9.
    1. Cheng VCC, Wong SC, To KKW, Ho PL, Yuen KY. Preparedness and proactive infection control measures against the emerging Wuhan coronavirus pneumonia in China. J Hosp Infect. 2020:pii: S0195-6701(20)30034–7. doi:10.1016/j.jhin.2020.01.010.

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