Skip to main content
SpringerLink
Log in

Coronavirus Entry Inhibitors

  • Chapter
  • First Online:
Virus Entry Inhibitors

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1366))

Abstract

Coronaviruses (CoVs) are enveloped RNA viruses that widely exist in the environment. Several CoVs possess a strong ability to infect humans, termed as human coronavirus (HCoVs). Among seven known HCoVs, SARS-CoV-2, SARS-CoV, and MERS-CoV belong to highly pathogenic HCoVs, which can cause severe clinical symptoms and even death. Especially, the current COVID-19 pandemic severely threatens human survival and health, which emphasizes the importance of developing effective CoV vaccines and anti-CoV agents to protect humans from HCoV infections. Coronavirus entry inhibitors can block various processes in viral entry, such as receptor binding, proteolytic activation of spike protein, or virus-cell membrane fusion. Coronavirus entry inhibitors, alone or in combination with other drugs, play important roles in the treatment of coronavirus diseases. Thus, we summarize and discuss the development of coronavirus entry inhibitors in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Amanat F, Thapa M, Lei T, Ahmed SMS, Adelsberg DC, Carreno JM, Strohmeier S, Schmitz AJ, Zafar S, Zhou JQ, Rijnink W, Alshammary H, Borcherding N, Reiche AG, Srivastava K, Sordillo EM, van Bakel H, Personalized Virology I, Turner JS, Bajic G, Simon V, Ellebedy AH, Krammer F (2021) SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2. Cell 184(15):3936–3948.e3910. https://doi.org/10.1016/j.cell.2021.06.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Apaydin CB, Cinar G, Cihan-Ustundag G (2021) Small-molecule antiviral agents in ongoing clinical trials for COVID-19. Curr Drug Targets 22:1986. https://doi.org/10.2174/1389450122666210215112150

    Article  CAS  PubMed  Google Scholar 

  • Arya R, Kumari S, Pandey B, Mistry H, Bihani SC, Das A, Prashar V, Gupta GD, Panicker L, Kumar M (2021) Structural insights into SARS-CoV-2 proteins. J Mol Biol 433(2):166725. https://doi.org/10.1016/j.jmb.2020.11.024

    Article  CAS  PubMed  Google Scholar 

  • Axfors C, Schmitt AM, Janiaud P, Van’t Hooft J, Abd-Elsalam S, Abdo EF, Abella BS, Akram J, Amaravadi RK, Angus DC, Arabi YM, Azhar S, Baden LR, Baker AW, Belkhir L, Benfield T, Berrevoets MAH, Chen CP, Chen TC, Cheng SH, Cheng CY, Chung WS, Cohen YZ, Cowan LN, Dalgard O, de Almeida EVFF, de Lacerda MVG, de Melo GC, Derde L, Dubee V, Elfakir A, Gordon AC, Hernandez-Cardenas CM, Hills T, Hoepelman AIM, Huang YW, Igau B, Jin R, Jurado-Camacho F, Khan KS, Kremsner PG, Kreuels B, Kuo CY, Le T, Lin YC, Lin WP, Lin TH, Lyngbakken MN, McArthur C, McVerry BJ, Meza-Meneses P, Monteiro WM, Morpeth SC, Mourad A, Mulligan MJ, Murthy S, Naggie S, Narayanasamy S, Nichol A, Novack LA, O’Brien SM, Okeke NL, Perez L, Perez-Padilla R, Perrin L, Remigio-Luna A, Rivera-Martinez NE, Rockhold FW, Rodriguez-Llamazares S, Rolfe R, Rosa R, Rosjo H, Sampaio VS, Seto TB, Shahzad M, Soliman S, Stout JE, Thirion-Romero I, Troxel AB, Tseng TY, Turner NA, Ulrich RJ, Walsh SR, Webb SA, Weehuizen JM, Velinova M, Wong HL, Wrenn R, Zampieri FG, Zhong W, Moher D, Goodman SN, Ioannidis JPA, Hemkens LG (2021) Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nat Commun 12(1):2349. https://doi.org/10.1038/s41467-021-22446-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bariola JR, McCreary EK, Wadas RJ, Kip KE, Marroquin OC, Minnier T, Koscumb S, Collins K, Schmidhofer M, Shovel JA, Wisniewski MK, Sullivan C, Yealy DM, Nace DA, Huang DT, Haidar G, Khadem T, Linstrum K, Seymour CW, Montgomery SK, Angus DC, Snyder GM (2021) Impact of bamlanivimab monoclonal antibody treatment on hospitalization and mortality among nonhospitalized adults with severe acute respiratory syndrome coronavirus 2 infection. Open Forum Infect Dis 8(7):ofab254. https://doi.org/10.1093/ofid/ofab254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baum A, Ajithdoss D, Copin R, Zhou A, Lanza K, Negron N, Ni M, Wei Y, Mohammadi K, Musser B, Atwal GS, Oyejide A, Goez-Gazi Y, Dutton J, Clemmons E, Staples HM, Bartley C, Klaffke B, Alfson K, Gazi M, Gonzalez O, Dick E Jr, Carrion R Jr, Pessaint L, Porto M, Cook A, Brown R, Ali V, Greenhouse J, Taylor T, Andersen H, Lewis MG, Stahl N, Murphy AJ, Yancopoulos GD, Kyratsous CA (2020) REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science 370(6520):1110–1115. https://doi.org/10.1126/science.abe2402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao L, Goreshnik I, Coventry B, Case JB, Miller L, Kozodoy L, Chen RE, Carter L, Walls AC, Park YJ, Strauch EM, Stewart L, Diamond MS, Veesler D, Baker D (2020) De novo design of picomolar SARS-CoV-2 miniprotein inhibitors. Science 370(6515):426–431. https://doi.org/10.1126/science.abd9909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Case JB, Chen RE, Cao L, Ying B, Winkler ES, Johnson M, Goreshnik I, Pham MN, Shrihari S, Kafai NM, Bailey AL, Xie X, Shi PY, Ravichandran R, Carter L, Stewart L, Baker D, Diamond MS (2021) Ultrapotent miniproteins targeting the SARS-CoV-2 receptor-binding domain protect against infection and disease. Cell Host Microbe 29(7):1151–1161.e1155. https://doi.org/10.1016/j.chom.2021.06.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ceccarelli G, Alessandri F, Oliva A, Borrazzo C, Dell’Isola S, Ialungo AM, Rastrelli E, Pelli M, Raponi G, Turriziani O, Ruberto F, Rocco M, Pugliese F, Russo A, d’Ettorre G, Venditti M (2021) The role of teicoplanin in the treatment of SARS-CoV-2 infection: a retrospective study in critically ill COVID-19 patients (Tei-COVID study). J Med Virol 93(7):4319–4325. https://doi.org/10.1002/jmv.26925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chan KK, Tan TJC, Narayanan KK, Procko E (2021) An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants. Sci Adv 7(8):eabf1738. https://doi.org/10.1126/sciadv.abf1738

    Article  PubMed  PubMed Central  Google Scholar 

  • Channappanavar R, Lu L, Xia S, Du L, Meyerholz DK, Perlman S, Jiang S (2015) Protective effect of intranasal regimens containing peptidic middle east respiratory syndrome coronavirus fusion inhibitor against MERS-CoV infection. J Infect Dis 212(12):1894–1903. https://doi.org/10.1093/infdis/jiv325

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Tian EK, He B, Tian L, Han R, Wang S, Xiang Q, Zhang S, El Arnaout T, Cheng W (2020) Overview of lethal human coronaviruses. Signal Transduct Target Ther 5(1):89. https://doi.org/10.1038/s41392-020-0190-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Adams AC, Van Naarden J, Custer KL, Shen L, Durante M, Oakley G, Schade AE, Sabo J, Patel DR, Klekotka P, Skovronsky DM, Investigators B (2021) SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with covid-19. N Engl J Med 384(3):229–237. https://doi.org/10.1056/NEJMoa2029849

    Article  CAS  PubMed  Google Scholar 

  • Cheng YW, Chao TL, Li CL, Chiu MF, Kao HC, Wang SH, Pang YH, Lin CH, Tsai YM, Lee WH, Tao MH, Ho TC, Wu PY, Jang LT, Chen PJ, Chang SY, Yeh SH (2020) Furin inhibitors block SARS-CoV-2 spike protein cleavage to suppress virus production and cytopathic effects. Cell Rep 33(2):108254. https://doi.org/10.1016/j.celrep.2020.108254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chi X, Yan R, Zhang J, Zhang G, Zhang Y, Hao M, Zhang Z, Fan P, Dong Y, Yang Y, Chen Z, Guo Y, Zhang J, Li Y, Song X, Chen Y, Xia L, Fu L, Hou L, Xu J, Yu C, Li J, Zhou Q, Chen W (2020) A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science 369(6504):650–655. https://doi.org/10.1126/science.abc6952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen MS, Nirula A, Mulligan MJ, Novak RM, Marovich M, Yen C, Stemer A, Mayer SM, Wohl D, Brengle B, Montague BT, Frank I, McCulloh RJ, Fichtenbaum CJ, Lipson B, Gabra N, Ramirez JA, Thai C, Chege W, Gomez Lorenzo MM, Sista N, Farrior J, Clement ME, Brown ER, Custer KL, Van Naarden J, Adams AC, Schade AE, Dabora MC, Knorr J, Price KL, Sabo J, Tuttle JL, Klekotka P, Shen L, Skovronsky DM, Investigators B (2021) Effect of bamlanivimab vs placebo on incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities: a randomized clinical trial. JAMA 326(1):46–55. https://doi.org/10.1001/jama.2021.8828

    Article  CAS  PubMed  Google Scholar 

  • Corti D, Purcell LA, Snell G, Veesler D (2021) Tackling COVID-19 with neutralizing monoclonal antibodies. Cell 184(12):3086–3108. https://doi.org/10.1016/j.cell.2021.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui J, Li F, Shi ZL (2019) Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 17(3):181–192. https://doi.org/10.1038/s41579-018-0118-9

    Article  CAS  PubMed  Google Scholar 

  • Daly JL, Simonetti B, Klein K, Chen KE, Williamson MK, Anton-Plagaro C, Shoemark DK, Simon-Gracia L, Bauer M, Hollandi R, Greber UF, Horvath P, Sessions RB, Helenius A, Hiscox JA, Teesalu T, Matthews DA, Davidson AD, Collins BM, Cullen PJ, Yamauchi Y (2020) Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 370(6518):861–865. https://doi.org/10.1126/science.abd3072

    Article  CAS  PubMed  Google Scholar 

  • Davies NG, Abbott S, Barnard RC, Jarvis CI, Kucharski AJ, Munday JD, Pearson CAB, Russell TW, Tully DC, Washburne AD, Wenseleers T, Gimma A, Waites W, Wong KLM, van Zandvoort K, Silverman JD, Diaz-Ordaz K, Keogh R, Eggo RM, Funk S, Jit M, Atkins KE, Edmunds WJ (2021) Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England. medRxiv:20248822. https://doi.org/10.1101/2020.12.24.20248822

  • Dougan M, Nirula A, Azizad M, Mocherla B, Gottlieb RL, Chen P, Hebert C, Perry R, Boscia J, Heller B, Morris J, Crystal C, Igbinadolor A, Huhn G, Cardona J, Shawa I, Kumar P, Adams AC, Van Naarden J, Custer KL, Durante M, Oakley G, Schade AE, Holzer TR, Ebert PJ, Higgs RE, Kallewaard NL, Sabo J, Patel DR, Dabora MC, Klekotka P, Shen L, Skovronsky DM, Investigators B (2021) Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19. N Engl J Med 385:1382. https://doi.org/10.1056/NEJMoa2102685

    Article  CAS  PubMed  Google Scholar 

  • Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S (2009) The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat Rev Microbiol 7(3):226–236. https://doi.org/10.1038/nrmicro2090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fung TS, Liu DX (2019) Human coronavirus: host-pathogen interaction. Annu Rev Microbiol 73:529–557. https://doi.org/10.1146/annurev-micro-020518-115759

    Article  CAS  PubMed  Google Scholar 

  • Gottlieb RL, Nirula A, Chen P, Boscia J, Heller B, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Kumar P, Adams AC, Van Naarden J, Custer KL, Durante M, Oakley G, Schade AE, Holzer TR, Ebert PJ, Higgs RE, Kallewaard NL, Sabo J, Patel DR, Klekotka P, Shen L, Skovronsky DM (2021) Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA 325(7):632–644. https://doi.org/10.1001/jama.2021.0202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gunst JD, Staerke NB, Pahus MH, Kristensen LH, Bodilsen J, Lohse N, Dalgaard LS, Bronnum D, Frobert O, Honge B, Johansen IS, Monrad I, Erikstrup C, Rosendal R, Vilstrup E, Mariager T, Bove DG, Offersen R, Shakar S, Cajander S, Jorgensen NP, Sritharan SS, Breining P, Jespersen S, Mortensen KL, Jensen ML, Kolte L, Frattari GS, Larsen CS, Storgaard M, Nielsen LP, Tolstrup M, Saedder EA, Ostergaard LJ, Ngo HTT, Jensen MH, Hojen JF, Kjolby M, Sogaard OS (2021) Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial. EClinicalMedicine 35:100849. https://doi.org/10.1016/j.eclinm.2021.100849

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo L, Bi W, Wang X, Xu W, Yan R, Zhang Y, Zhao K, Li Y, Zhang M, Cai X, Jiang S, Xie Y, Zhou Q, Lu L, Dang B (2021) Engineered trimeric ACE2 binds viral spike protein and locks it in “Three-up” conformation to potently inhibit SARS-CoV-2 infection. Cell Res 31(1):98–100. https://doi.org/10.1038/s41422-020-00438-w

    Article  CAS  PubMed  Google Scholar 

  • Hansen J, Baum A, Pascal KE, Russo V, Giordano S, Wloga E, Fulton BO, Yan Y, Koon K, Patel K, Chung KM, Hermann A, Ullman E, Cruz J, Rafique A, Huang T, Fairhurst J, Libertiny C, Malbec M, Lee WY, Welsh R, Farr G, Pennington S, Deshpande D, Cheng J, Watty A, Bouffard P, Babb R, Levenkova N, Chen C, Zhang B, Romero Hernandez A, Saotome K, Zhou Y, Franklin M, Sivapalasingam S, Lye DC, Weston S, Logue J, Haupt R, Frieman M, Chen G, Olson W, Murphy AJ, Stahl N, Yancopoulos GD, Kyratsous CA (2020) Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369(6506):1010–1014. https://doi.org/10.1126/science.abd0827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S (2020a) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2):271–280.e278. https://doi.org/10.1016/j.cell.2020.02.052

    Article  PubMed  PubMed Central  Google Scholar 

  • Hoffmann M, Mosbauer K, Hofmann-Winkler H, Kaul A, Kleine-Weber H, Kruger N, Gassen NC, Muller MA, Drosten C, Pohlmann S (2020b) Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. Nature 585(7826):588–590. https://doi.org/10.1038/s41586-020-2575-3

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann M, Arora P, Groß R, Seidel A, Hörnich BF, Hahn AS, Krüger N, Graichen L, Hofmann-Winkler H, Kempf A, Winkler MS, Schulz S, Jäck HM, Jahrsdörfer B, Schrezenmeier H, Müller M, Kleger A, Münch J, Pöhlmann S (2021a) SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184(9):2384–2393.e2312. https://doi.org/10.1016/j.cell.2021.03.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann M, Hofmann-Winkler H, Kruger N, Kempf A, Nehlmeier I, Graichen L, Arora P, Sidarovich A, Moldenhauer AS, Winkler MS, Schulz S, Jack HM, Stankov MV, Behrens GMN, Pohlmann S (2021b) SARS-CoV-2 variant B.1.617 is resistant to bamlanivimab and evades antibodies induced by infection and vaccination. Cell Rep 36(3):109415. https://doi.org/10.1016/j.celrep.2021.109415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hofmann H, Geier M, Marzi A, Krumbiegel M, Peipp M, Fey GH, Gramberg T, Pohlmann S (2004) Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor. Biochem Biophys Res Commun 319(4):1216–1221. https://doi.org/10.1016/j.bbrc.2004.05.114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu B, Guo H, Zhou P, Shi ZL (2021) Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol 19(3):141–154. https://doi.org/10.1038/s41579-020-00459-7

    Article  CAS  PubMed  Google Scholar 

  • Hui DS (2016) Super-spreading events of MERS-CoV infection. Lancet 388(10048):942–943. https://doi.org/10.1016/S0140-6736(16)30828-5

    Article  PubMed  PubMed Central  Google Scholar 

  • Inn KS, Kim Y, Aigerim A, Park U, Hwang ES, Choi MS, Kim YS, Cho NH (2018) Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected with Middle East respiratory syndrome coronavirus. Virology 518:324–327. https://doi.org/10.1016/j.virol.2018.03.015

    Article  CAS  PubMed  Google Scholar 

  • Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, Thomas WD Jr, Thackray LB, Young MD, Mason RJ, Ambrosino DM, Wentworth DE, Demartini JC, Holmes KV (2004) CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A 101(44):15748–15753. https://doi.org/10.1073/pnas.0403812101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiaming L, Yanfeng Y, Yao D, Yawei H, Linlin B, Baoying H, Jinghua Y, Gao GF, Chuan Q, Wenjie T (2017) The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Vaccine 35(1):10–18. https://doi.org/10.1016/j.vaccine.2016.11.064

    Article  CAS  PubMed  Google Scholar 

  • Jiang S, Du L (2020) Effect of low-pathogenic human coronavirus-specific antibodies on SARS-CoV-2. Trends Immunol 41(10):853–854. https://doi.org/10.1016/j.it.2020.08.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang L, Wang N, Zuo T, Shi X, Poon KM, Wu Y, Gao F, Li D, Wang R, Guo J, Fu L, Yuen KY, Zheng BJ, Wang X, Zhang L (2014) Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci Transl Med 6(234):234ra259. https://doi.org/10.1126/scitranslmed.3008140

    Article  CAS  Google Scholar 

  • Jiang S, Hillyer C, Du L (2020) Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends Immunol 41(5):355–359. https://doi.org/10.1016/j.it.2020.03.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson BA, Xie X, Bailey AL, Kalveram B, Lokugamage KG, Muruato A, Zou J, Zhang X, Juelich T, Smith JK, Zhang L, Bopp N, Schindewolf C, Vu M, Vanderheiden A, Winkler ES, Swetnam D, Plante JA, Aguilar P, Plante KS, Popov V, Lee B, Weaver SC, Suthar MS, Routh AL, Ren P, Ku Z, An Z, Debbink K, Diamond MS, Shi PY, Freiberg AN, Menachery VD (2021) Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature 591(7849):293–299. https://doi.org/10.1038/s41586-021-03237-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones BE, Brown-Augsburger PL, Corbett KS, Westendorf K, Davies J, Cujec TP, Wiethoff CM, Blackbourne JL, Heinz BA, Foster D, Higgs RE, Balasubramaniam D, Wang L, Zhang Y, Yang ES, Bidshahri R, Kraft L, Hwang Y, Zentelis S, Jepson KR, Goya R, Smith MA, Collins DW, Hinshaw SJ, Tycho SA, Pellacani D, Xiang P, Muthuraman K, Sobhanifar S, Piper MH, Triana FJ, Hendle J, Pustilnik A, Adams AC, Berens SJ, Baric RS, Martinez DR, Cross RW, Geisbert TW, Borisevich V, Abiona O, Belli HM, de Vries M, Mohamed A, Dittmann M, Samanovic MI, Mulligan MJ, Goldsmith JA, Hsieh CL, Johnson NV, Wrapp D, McLellan JS, Barnhart BC, Graham BS, Mascola JR, Hansen CL, Falconer E (2021) The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med 13(593):eabf1906. https://doi.org/10.1126/scitranslmed.abf1906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ju B, Zhang Q, Ge J, Wang R, Sun J, Ge X, Yu J, Shan S, Zhou B, Song S, Tang X, Yu J, Lan J, Yuan J, Wang H, Zhao J, Zhang S, Wang Y, Shi X, Liu L, Zhao J, Wang X, Zhang Z, Zhang L. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020 Aug;584(7819):115-119. https://doi.org/10.1038/s41586-020-2380-z

    Google Scholar 

  • Kang YL, Chou YY, Rothlauf PW, Liu Z, Soh TK, Cureton D, Case JB, Chen RE, Diamond MS, Whelan SPJ, Kirchhausen T (2020) Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. Proc Natl Acad Sci U S A 117(34):20803–20813. https://doi.org/10.1073/pnas.2007837117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lang Y, Li W, Li Z, Koerhuis D, van den Burg ACS, Rozemuller E, Bosch BJ, van Kuppeveld FJM, Boons GJ, Huizinga EG, van der Schaar HM, de Groot RJ (2020) Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity. Proc Natl Acad Sci U S A 117(41):25759–25770. https://doi.org/10.1073/pnas.2006299117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Wan Y, Liu P, Zhao J, Lu G, Qi J, Wang Q, Lu X, Wu Y, Liu W, Zhang B, Yuen KY, Perlman S, Gao GF, Yan J (2015) A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein. Cell Res 25(11):1237–1249. https://doi.org/10.1038/cr.2015.113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, Kong Y, Ren L, Wei Q, Mei H, Hu C, Tao C, Yang R, Wang J, Yu Y, Guo Y, Wu X, Xu Z, Zeng L, Xiong N, Chen L, Wang J, Man N, Liu Y, Xu H, Deng E, Zhang X, Li C, Wang C, Su S, Zhang L, Wang J, Wu Y, Liu Z (2020a) Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA 324(5):460–470. https://doi.org/10.1001/jama.2020.10044

    Article  CAS  PubMed  Google Scholar 

  • Li X, Wang Y, Agostinis P, Rabson A, Melino G, Carafoli E, Shi Y, Sun E (2020b) Is hydroxychloroquine beneficial for COVID-19 patients? Cell Death Dis 11(7):512. https://doi.org/10.1038/s41419-020-2721-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lip KM, Shen S, Yang X, Keng CT, Zhang A, Oh HL, Li ZH, Hwang LA, Chou CF, Fielding BC, Tan TH, Mayrhofer J, Falkner FG, Fu J, Lim SG, Hong W, Tan YJ (2006) Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus. J Virol 80(2):941–950. https://doi.org/10.1128/JVI.80.2.941-950.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Xiao G, Chen Y, He Y, Niu J, Escalante CR, Xiong H, Farmar J, Debnath AK, Tien P, Jiang S (2004) Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet 363(9413):938–947. https://doi.org/10.1016/S0140-6736(04)15788-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu DX, Fung TS, Chong KK, Shukla A, Hilgenfeld R (2014) Accessory proteins of SARS-CoV and other coronaviruses. Antivir Res 109:97–109. https://doi.org/10.1016/j.antiviral.2014.06.013

    Article  CAS  PubMed  Google Scholar 

  • Lu L, Liu Q, Zhu Y, Chan KH, Qin L, Li Y, Wang Q, Chan JF, Du L, Yu F, Ma C, Ye S, Yuen KY, Zhang R, Jiang S (2014) Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat Commun 5(1):3067. https://doi.org/10.1038/ncomms4067

    Article  CAS  PubMed  Google Scholar 

  • Ma Z, Li P, Ji Y, Ikram A, Pan Q (2020) Cross-reactivity towards SARS-CoV-2: the potential role of low-pathogenic human coronaviruses. Lancet Microbe 1(4):e151. https://doi.org/10.1016/S2666-5247(20)30098-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuyama S, Shirato K, Kawase M, Terada Y, Kawachi K, Fukushi S, Kamitani W (2018) Middle east respiratory syndrome coronavirus spike protein is not activated directly by cellular furin during viral entry into target cells. J Virol 92(19):e00683–e00618. https://doi.org/10.1128/JVI.00683-18

    Article  PubMed  PubMed Central  Google Scholar 

  • McBride R, van Zyl M, Fielding BC (2014) The coronavirus nucleocapsid is a multifunctional protein. Viruses 6(8):2991–3018. https://doi.org/10.3390/v6082991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCallum M, De Marco A, Lempp FA, Tortorici MA, Pinto D, Walls AC, Beltramello M, Chen A, Liu Z, Zatta F, Zepeda S, di Iulio J, Bowen JE, Montiel-Ruiz M, Zhou J, Rosen LE, Bianchi S, Guarino B, Fregni CS, Abdelnabi R, Foo SC, Rothlauf PW, Bloyet LM, Benigni F, Cameroni E, Neyts J, Riva A, Snell G, Telenti A, Whelan SPJ, Virgin HW, Corti D, Pizzuto MS, Veesler D (2021) N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184(9):2332–2347.e2316. https://doi.org/10.1016/j.cell.2021.03.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mellott DM, Tseng CT, Drelich A, Fajtova P, Chenna BC, Kostomiris DH, Hsu J, Zhu J, Taylor ZW, Kocurek KI, Tat V, Katzfuss A, Li L, Giardini MA, Skinner D, Hirata K, Yoon MC, Beck S, Carlin AF, Clark AE, Beretta L, Maneval D, Hook V, Frueh F, Hurst BL, Wang H, Raushel FM, O’Donoghue AJ, de Siqueira-Neto JL, Meek TD, McKerrow JH (2021) A clinical-stage cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells. ACS Chem Biol 16(4):642–650. https://doi.org/10.1021/acschembio.0c00875

    Article  CAS  PubMed  Google Scholar 

  • ter Meulen J, van den Brink EN, Poon LL, Marissen WE, Leung CS, Cox F, Cheung CY, Bakker AQ, Bogaards JA, van Deventer E, Preiser W, Doerr HW, Chow VT, de Kruif J, Peiris JS, Goudsmit J (2006) Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med 3(7):e237. https://doi.org/10.1371/journal.pmed.0030237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monteil V, Kwon H, Prado P, Hagelkruys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, Hurtado Del Pozo C, Prosper F, Romero JP, Wirnsberger G, Zhang H, Slutsky AS, Conder R, Montserrat N, Mirazimi A, Penninger JM (2020) Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 181(4):905–913.e907. https://doi.org/10.1016/j.cell.2020.04.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohnuma K, Haagmans BL, Hatano R, Raj VS, Mou H, Iwata S, Dang NH, Bosch BJ, Morimoto C (2013) Inhibition of Middle East respiratory syndrome coronavirus infection by anti-CD26 monoclonal antibody. J Virol 87(24):13892–13899. https://doi.org/10.1128/JVI.02448-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pallesen J, Wang N, Corbett KS, Wrapp D, Kirchdoerfer RN, Turner HL, Cottrell CA, Becker MM, Wang L, Shi W, Kong WP, Andres EL, Kettenbach AN, Denison MR, Chappell JD, Graham BS, Ward AB, McLellan JS (2017) Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc Natl Acad Sci U S A 114(35):E7348–E7357. https://doi.org/10.1073/pnas.1707304114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park JE, Gallagher T (2017) Lipidation increases antiviral activities of coronavirus fusion-inhibiting peptides. Virology 511:9–18. https://doi.org/10.1016/j.virol.2017.07.033

    Article  CAS  PubMed  Google Scholar 

  • Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, Hunt C, Strein J, Berrebi A, Sisk JM, Matthews KL, Babb R, Chen G, Lai KM, Huang TT, Olson W, Yancopoulos GD, Stahl N, Frieman MB, Kyratsous CA (2015) Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection. Proc Natl Acad Sci U S A 112(28):8738–8743. https://doi.org/10.1073/pnas.1510830112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinana JL, Xhaard A, Tridello G, Passweg J, Kozijn A, Polverelli N, Heras I, Perez A, Sanz J, Berghuis D, Vazquez L, Suarez-Lledo M, Itala-Remes M, Ozcelik T, Iturrate Basaran I, Karakukcu M, Al Zahrani M, Choi G, Cuesta Casas MA, Batlle Massana M, Viviana A, Blijlevens N, Ganser A, Kuskonmaz B, Labussiere-Wallet H, Shaw PJ, Arzu Yegin Z, Gonzalez-Vicent M, Rocha V, Ferster A, Knelange N, Navarro D, Mikulska M, de la Camara R, Styczynski J (2021) Seasonal human coronavirus respiratory tract infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis 223(9):1564–1575. https://doi.org/10.1093/infdis/jiaa553

    Article  CAS  PubMed  Google Scholar 

  • Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, Rajah MM, Planchais C, Porrot F, Robillard N, Puech J, Prot M, Gallais F, Gantner P, Velay A, Le Guen J, Kassis-Chikhani N, Edriss D, Belec L, Seve A, Courtellemont L, Pere H, Hocqueloux L, Fafi-Kremer S, Prazuck T, Mouquet H, Bruel T, Simon-Loriere E, Rey FA, Schwartz O (2021) Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596:276. https://doi.org/10.1038/s41586-021-03777-9

    Article  CAS  PubMed  Google Scholar 

  • Raj VS, Smits SL, Provacia LB, van den Brand JM, Wiersma L, Ouwendijk WJ, Bestebroer TM, Spronken MI, van Amerongen G, Rottier PJ, Fouchier RA, Bosch BJ, Osterhaus AD, Haagmans BL (2014) Adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase 4-mediated entry of the Middle East respiratory syndrome coronavirus. J Virol 88(3):1834–1838. https://doi.org/10.1128/JVI.02935-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rey FA, Lok SM (2018) Common features of enveloped viruses and implications for immunogen design for next-generation vaccines. Cell 172(6):1319–1334. https://doi.org/10.1016/j.cell.2018.02.054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schoeman D, Fielding BC (2019) Coronavirus envelope protein: current knowledge. Virol J 16(1):69. https://doi.org/10.1186/s12985-019-1182-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A, Li F (2020) Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A 117(21):11727–11734. https://doi.org/10.1073/pnas.2003138117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen X, Tang H, Pajon R, Smith G, Glenn GM, Shi W, Korber B, Montefiori DC (2021) Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351. N Engl J Med 384(24):2352–2354. https://doi.org/10.1056/NEJMc2103740

    Article  CAS  PubMed  Google Scholar 

  • Simonis A, Theobald SJ, Fatkenheuer G, Rybniker J, Malin JJ (2021) A comparative analysis of remdesivir and other repurposed antivirals against SARS-CoV-2. EMBO Mol Med 13(1):e13105. https://doi.org/10.15252/emmm.202013105

    Article  CAS  PubMed  Google Scholar 

  • Simonovich VA, Burgos Pratx LD, Scibona P, Beruto MV, Vallone MG, Vazquez C, Savoy N, Giunta DH, Perez LG, Sanchez MDL, Gamarnik AV, Ojeda DS, Santoro DM, Camino PJ, Antelo S, Rainero K, Vidiella GP, Miyazaki EA, Cornistein W, Trabadelo OA, Ross FM, Spotti M, Funtowicz G, Scordo WE, Losso MH, Ferniot I, Pardo PE, Rodriguez E, Rucci P, Pasquali J, Fuentes NA, Esperatti M, Speroni GA, Nannini EC, Matteaccio A, Michelangelo HG, Follmann D, Lane HC, Belloso WH, PlasmAr Study G (2021) A randomized trial of convalescent plasma in covid-19 severe pneumonia. N Engl J Med 384(7):619–629. https://doi.org/10.1056/NEJMoa2031304

    Article  CAS  PubMed  Google Scholar 

  • Sivapalasingam S, Saviolakis GA, Kulcsar K, Nakamura A, Conrad T, Hassanein M, Sumner G, Elango C, Kamal MA, Eng S, Kyratsous CA, Musser BJ, Frieman M, Kantrowitz J, Weinreich DM, Yancopoulos G, Stahl N, Lipsich L (2021) Human monoclonal antibody cocktail for the treatment or prophylaxis of middle eastern respiratory syndrome coronavirus (MERS-CoV). J Infect Dis:jiab036. https://doi.org/10.1093/infdis/jiab036

  • Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, Liu W, Bi Y, Gao GF (2016) Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol 24(6):490–502. https://doi.org/10.1016/j.tim.2016.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK, Moore MJ, Tallarico AS, Olurinde M, Choe H, Anderson LJ, Bellini WJ, Farzan M, Marasco WA (2004) Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci U S A 101(8):2536–2541. https://doi.org/10.1073/pnas.0307140101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung JJ, Yu I, Zhong NS, Tsoi K (2009) Super-spreading events of SARS in a hospital setting: who, when, and why? Hong Kong Med J 15(Suppl 8):29–33

    PubMed  Google Scholar 

  • Tada T, Fan C, Chen JS, Kaur R, Stapleford KA, Gristick H, Dcosta BM, Wilen CB, Nimigean CM, Landau NR (2020) An ACE2 microbody containing a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2. Cell Rep 33(12):108528. https://doi.org/10.1016/j.celrep.2020.108528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor PC, Adams AC, Hufford MM, de la Torre I, Winthrop K, Gottlieb RL (2021) Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol 21(6):382–393. https://doi.org/10.1038/s41577-021-00542-x

    Article  CAS  PubMed  Google Scholar 

  • Tortorici MA, Veesler D (2019) Structural insights into coronavirus entry. Adv Virus Res 105:93–116. https://doi.org/10.1016/bs.aivir.2019.08.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tuccori M, Ferraro S, Convertino I, Cappello E, Valdiserra G, Blandizzi C, Maggi F, Focosi D (2020) Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline. MAbs 12(1):1854149. https://doi.org/10.1080/19420862.2020.1854149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • V’Kovski P, Kratzel A, Steiner S, Stalder H, Thiel V (2021) Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 19(3):155–170. https://doi.org/10.1038/s41579-020-00468-6

    Article  CAS  PubMed  Google Scholar 

  • Verderese JP, Stepanova M, Lam B, Racila A, Kolacevski A, Allen D, Hodson E, Aslani-Amoli B, Homeyer M, Stanmyre S, Stevens H, Garofalo S, Henry L, Venkatesan C, Gerber LH, Motew S, Jones JS, Younossi ZM (2021) Neutralizing monoclonal antibody treatment reduces hospitalization for mild and moderate COVID-19: a real-world experience. Clin Infect Dis:ciab579. https://doi.org/10.1093/cid/ciab579

  • de Vries RD, Schmitz KS, Bovier FT, Predella C, Khao J, Noack D, Haagmans BL, Herfst S, Stearns KN, Drew-Bear J, Biswas S, Rockx B, McGill G, Dorrello NV, Gellman SH, Alabi CA, de Swart RL, Moscona A, Porotto M (2021) Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets. Science 371(6536):1379–1382. https://doi.org/10.1126/science.abf4896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Shi W, Joyce MG, Modjarrad K, Zhang Y, Leung K, Lees CR, Zhou T, Yassine HM, Kanekiyo M, Yang ZY, Chen X, Becker MM, Freeman M, Vogel L, Johnson JC, Olinger G, Todd JP, Bagci U, Solomon J, Mollura DJ, Hensley L, Jahrling P, Denison MR, Rao SS, Subbarao K, Kwong PD, Mascola JR, Kong WP, Graham BS (2015) Evaluation of candidate vaccine approaches for MERS-CoV. Nat Commun 6(1):7712. https://doi.org/10.1038/ncomms8712

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Shi W, Chappell JD, Joyce MG, Zhang Y, Kanekiyo M, Becker MM, van Doremalen N, Fischer R, Wang N, Corbett KS, Choe M, Mason RD, Van Galen JG, Zhou T, Saunders KO, Tatti KM, Haynes LM, Kwong PD, Modjarrad K, Kong WP, McLellan JS, Denison MR, Munster VJ, Mascola JR, Graham BS (2018) Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on the Middle East respiratory syndrome coronavirus spike glycoprotein to avoid neutralization escape. J Virol 92(10):e02002–e02017. https://doi.org/10.1128/JVI.02002-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang C, Hua C, Xia S, Li W, Lu L, Jiang S (2019a) Combining a fusion inhibitory peptide targeting the MERS-CoV S2 protein HR1 domain and a neutralizing antibody specific for the S1 protein receptor-binding domain (RBD) showed potent synergism against pseudotyped MERS-CoV with or without mutations in RBD. Viruses 11(1):31. https://doi.org/10.3390/v11010031

    Article  CAS  PubMed Central  Google Scholar 

  • Wang L, Xu J, Kong Y, Liang R, Li W, Li J, Lu J, Dimitrov DS, Yu F, Wu Y, Ying T (2019b) Engineering a novel antibody-peptide bispecific fusion protein against MERS-CoV. Antibodies (Basel) 8(4):10.3390/antib8040053

    Google Scholar 

  • Wang N, Rosen O, Wang L, Turner HL, Stevens LJ, Corbett KS, Bowman CA, Pallesen J, Shi W, Zhang Y, Leung K, Kirchdoerfer RN, Becker MM, Denison MR, Chappell JD, Ward AB, Graham BS, McLellan JS (2019c) Structural definition of a neutralization-sensitive epitope on the MERS-CoV S1-NTD. Cell Rep 28(13):3395–3405.e3396. https://doi.org/10.1016/j.celrep.2019.08.052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang S, Li W, Hui H, Tiwari SK, Zhang Q, Croker BA, Rawlings S, Smith D, Carlin AF, Rana TM (2020) Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol. EMBO J 39(21):e106057. https://doi.org/10.15252/embj.2020106057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang C, van Haperen R, Gutierrez-Alvarez J, Li W, Okba NMA, Albulescu I, Widjaja I, van Dieren B, Fernandez-Delgado R, Sola I, Hurdiss DL, Daramola O, Grosveld F, van Kuppeveld FJM, Haagmans BL, Enjuanes L, Drabek D, Bosch BJ (2021a) A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies. Nat Commun 12(1):1715. https://doi.org/10.1038/s41467-021-21968-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang G, Yang ML, Duan ZL, Liu FL, Jin L, Long CB, Zhang M, Tang XP, Xu L, Li YC, Kamau PM, Yang L, Liu HQ, Xu JW, Chen JK, Zheng YT, Peng XZ, Lai R (2021b) Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models. Cell Res 31(1):17–24. https://doi.org/10.1038/s41422-020-00450-0

    Article  CAS  PubMed  Google Scholar 

  • Wang P, Nair MS, Liu L, Iketani S, Luo Y, Guo Y, Wang M, Yu J, Zhang B, Kwong PD, Graham BS, Mascola JR, Chang JY, Yin MT, Sobieszczyk M, Kyratsous CA, Shapiro L, Sheng Z, Huang Y, Ho DD (2021c) Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593(7857):130–135. https://doi.org/10.1038/s41586-021-03398-2

    Article  CAS  PubMed  Google Scholar 

  • Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Trial I (2021) REGN-COV2, a neutralizing antibody cocktail, in outpatients with covid-19. N Engl J Med 384(3):238–251. https://doi.org/10.1056/NEJMoa2035002

    Article  CAS  PubMed  Google Scholar 

  • Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC (2020) Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA 324(8):782–793. https://doi.org/10.1001/jama.2020.12839

    Article  CAS  PubMed  Google Scholar 

  • de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ (2014) Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 58(8):4875–4884. https://doi.org/10.1128/AAC.03011-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Wit E, van Doremalen N, Falzarano D, Munster VJ (2016) SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 14(8):523–534. https://doi.org/10.1038/nrmicro.2016.81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia S, Yan L, Xu W, Agrawal AS, Algaissi A, Tseng CK, Wang Q, Du L, Tan W, Wilson IA, Jiang S, Yang B, Lu L (2019) A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike. Sci Adv 5(4):eaav4580. https://doi.org/10.1126/sciadv.aav4580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia S, Lan Q, Su S, Wang X, Xu W, Liu Z, Zhu Y, Wang Q, Lu L, Jiang S (2020a) The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin. Signal Transduct Target Ther 5(1):92. https://doi.org/10.1038/s41392-020-0184-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S, Qi F, Bao L, Du L, Liu S, Qin C, Sun F, Shi Z, Zhu Y, Jiang S, Lu L (2020b) Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res 30(4):343–355. https://doi.org/10.1038/s41422-020-0305-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia S, Zhu Y, Liu M, Lan Q, Xu W, Wu Y, Ying T, Liu S, Shi Z, Jiang S, Lu L (2020c) Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell Mol Immunol 17(7):765–767. https://doi.org/10.1038/s41423-020-0374-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav R, Chaudhary JK, Jain N, Chaudhary PK, Khanra S, Dhamija P, Sharma A, Kumar A, Handu S (2021) Role of structural and non-structural proteins and therapeutic targets of SARS-CoV-2 for COVID-19. Cells 10(4):821. https://doi.org/10.3390/cells10040821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamoto M, Kiso M, Sakai-Tagawa Y, Iwatsuki-Horimoto K, Imai M, Takeda M, Kinoshita N, Ohmagari N, Gohda J, Semba K, Matsuda Z, Kawaguchi Y, Kawaoka Y, Inoue JI (2020) The anticoagulant nafamostat potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and viral infection in vitro in a cell-type-dependent manner. Viruses 12(6):629. https://doi.org/10.3390/v12060629

    Article  CAS  PubMed Central  Google Scholar 

  • Ying T, Prabakaran P, Du L, Shi W, Feng Y, Wang Y, Wang L, Li W, Jiang S, Dimitrov DS, Zhou T (2015) Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. Nat Commun 6:8223. https://doi.org/10.1038/ncomms9223

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Li HB, Lyu JR, Lei XM, Li W, Wu G, Lyu J, Dai ZM (2020) Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection. Int J Infect Dis 96:19–24. https://doi.org/10.1016/j.ijid.2020.04.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang AR, Shi WQ, Liu K, Li XL, Liu MJ, Zhang WH, Zhao GP, Chen JJ, Zhang XA, Miao D, Ma W, Liu W, Yang Y, Fang LQ (2021) Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012-2020. Infect Dis Poverty 10(1):66. https://doi.org/10.1186/s40249-021-00853-0

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao H, To KKW, Lam H, Zhou X, Chan JF, Peng Z, Lee ACY, Cai J, Chan WM, Ip JD, Chan CC, Yeung ML, Zhang AJ, Chu AWH, Jiang S, Yuen KY (2021) Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2. Nat Commun 12(1):1517. https://doi.org/10.1038/s41467-021-21825-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou N, Pan T, Zhang J, Li Q, Zhang X, Bai C, Huang F, Peng T, Zhang J, Liu C, Tao L, Zhang H (2016) Glycopeptide antibiotics potently inhibit cathepsin L in the late endosome/lysosome and block the entry of ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus (SARS-CoV). J Biol Chem 291(17):9218–9232. https://doi.org/10.1074/jbc.M116.716100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou H, Chen Y, Zhang S, Niu P, Qin K, Jia W, Huang B, Zhang S, Lan J, Zhang L, Tan W, Wang X (2019) Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein. Nat Commun 10(1):3068. https://doi.org/10.1038/s41467-019-10897-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798):270–273. https://doi.org/10.1038/s41586-020-2012-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou B, Thao TTN, Hoffmann D, Taddeo A, Ebert N, Labroussaa F, Pohlmann A, King J, Steiner S, Kelly JN, Portmann J, Halwe NJ, Ulrich L, Trueb BS, Fan X, Hoffmann B, Wang L, Thomann L, Lin X, Stalder H, Pozzi B, de Brot S, Jiang N, Cui D, Hossain J, Wilson MM, Keller MW, Stark TJ, Barnes JR, Dijkman R, Jores J, Benarafa C, Wentworth DE, Thiel V, Beer M (2021) SARS-CoV-2 spike D614G change enhances replication and transmission. Nature 592(7852):122–127. https://doi.org/10.1038/s41586-021-03361-1

    Article  CAS  PubMed  Google Scholar 

  • Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W, China Novel Coronavirus I, and Research T (2020a) A novel coronavirus from patients with pneumonia in china, 2019. N Engl J Med 382(8):727–733. https://doi.org/10.1056/NEJMoa2001017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Y, Yu D, Yan H, Chong H, He Y (2020b) Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity. J Virol 94(14):e00635–e00620. https://doi.org/10.1128/JVI.00635-20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, Seitz T, Traugott M, Grieb A, Pawelka E, Laferl H, Wenisch C, Neuhold S, Haider D, Stiasny K, Bergthaler A, Puchhammer-Stoeckl E, Mirazimi A, Montserrat N, Zhang H, Slutsky AS, Penninger JM (2020) Human recombinant soluble ACE2 in severe COVID-19. Lancet Respir Med 8(11):1154–1158. https://doi.org/10.1016/S2213-2600(20)30418-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY (2016) Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov 15(5):327–347. https://doi.org/10.1038/nrd.2015.37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

    Qiaoshuai Lan, Shuai Xia & Lu Lu

Authors
  1. Qiaoshuai Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuai Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lu Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lu Lu .

Editor information

Editors and Affiliations

  1. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

    Shibo Jiang

  2. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

    Lu Lu

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lan, Q., Xia, S., Lu, L. (2022). Coronavirus Entry Inhibitors. In: Jiang, S., Lu, L. (eds) Virus Entry Inhibitors. Advances in Experimental Medicine and Biology, vol 1366. Springer, Singapore. https://doi.org/10.1007/978-981-16-8702-0_7

Download citation

Publish with us

Policies and ethics

Search

Navigation