Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Current Frontiers

Progress in Studies on Structural and Remedial Aspects of Newly Born Coronavirus, SARS-CoV-2

Author(s): Satya P. Gupta*

Volume 20 , Issue 26 , 2020

Page: [2362 - 2378] Pages: 17

DOI: 10.2174/1568026620666200922112300

Price: $65


The article highlights an up-to-date progress in studies on structural and the remedial aspects of novel coronavirus 2019-nCoV, renamed as SARS-CoV-2, leading to the disease COVID-19, a pandemic. In general, all CoVs including SARS-CoV-2 are spherical positive single-stranded RNA viruses containing spike (S) protein, envelope (E) protein, nucleocapsid (N) protein, and membrane (M) protein, where S protein has a Receptor-binding Domain (RBD) that mediates the binding to host cell receptor, Angiotensin Converting Enzyme 2 (ACE2). The article details the repurposing of some drugs to be tried for COVID-19 and presents the status of vaccine development so far. Besides drugs and vaccines, the role of Convalescent Plasma (CP) therapy to treat COVID-19 is also discussed.

Keywords: 2019-CoV-2, COVID-19, Anti-COVID-19 drugs, Vaccines, Convalescent plasma (CP) therapy, Epitopes, Antibodies.

Graphical Abstract
Woo, P.C.; Huang, Y.; Lau, S.K.; Yuen, K.Y. Coronavirus genomics and bioinformatics analysis. Viruses, 2010, 2(8), 1804-1820.
[ ] [PMID: 21994708]
Woo, P.C.; Lau, S.K.; Lam, C.S.; Lau, C.C.; Tsang, A.K.; Lau, J.H.; Bai, R.; Teng, J.L.; Tsang, C.C.; Wang, M.; Zheng, B.J.; Chan, K.H.; Yuen, K.Y. Discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J. Virol., 2012, 86(7), 3995-4008.
[ ] [PMID: 22278237]
Ashour, H.M.; Elkhatib, W.F.; Rahman, M.M.; Elshabrawy, H.A.; Elshabrawy, H.A. Insights into the recent 2019 novel coronavirus (SARS- CoV-2) in light of past human coronavirus outbreaks. Pathogens, 2020, 9(3), 186.
[ ] [PMID: 32143502]
Drosten, C.; Günther, S.; Preiser, W.; van der Werf, S.; Brodt, H.R.; Becker, S.; Rabenau, H.; Panning, M.; Kolesnikova, L.; Fouchier, R.A.; Berger, A.; Burguière, A.M.; Cinatl, J.; Eickmann, M.; Escriou, N.; Grywna, K.; Kramme, S.; Manuguerra, J.C.; Müller, S.; Rickerts, V.; Stürmer, M.; Vieth, S.; Klenk, H.D.; Osterhaus, A.D.; Schmitz, H.; Doerr, H.W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med., 2003, 348(20), 1967-1976.
[ ] [PMID: 12690091]
Zaki, A.M.; van Boheemen, S.; Bestebroer, T.M.; Osterhaus, A.D.; Fouchier, R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med., 2012, 367(19), 1814-1820.
[ ] [PMID: 23075143]
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, G.F.; Tan, W. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in china, 2019. N. Engl. J. Med., 2020, 382(8), 727-733.
[ ] [PMID: 31978945]
Rothe, C.; Schunk, M.; Sothmann, P.; Bretzel, G.; Froeschl, G.; Wallrauch, C.; Zimmer, T.; Thiel, V.; Janke, C.; Guggemos, W.; Seilmaier, M.; Drosten, C.; Vollmar, P.; Zwirglmaier, K.; Zange, S.; Wölfel, R.; Hoelscher, M. Transmission of 2019-nCoV infection from an asymptomatic contact in germany. N. Engl. J. Med., 2020, 382(10), 970-971.
[ ] [PMID: 32003551]
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W.J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020, 395(10224), 565-574.
[ ] [PMID: 32007145]
Barcena, M.; Oostergetel, G.T.; Bartelink, W.; Faas, F.G.; Verkleij, A.; Rottier, P.J.; Koster, A.J.; Bosch, B.J. Cryo-electron tomography of mouse hepatitis virus: Insights into the structure of the coronavirion. Proc. Natl. Acad. Sci. USA, 2009, 106(2), 582-587.
[ ] [PMID: 19124777]
Neuman, B.W.; Adair, B.D.; Yoshioka, C.; Quispe, J.D.; Orca, G.; Kuhn, P.; Milligan, R.A.; Yeager, M.; Buchmeier, M.J. Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy. J. Virol., 2006, 80(16), 7918-7928.
[ ] [PMID: 16873249]
Fehr, A.R.; Perlman, S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol. Biol., 2015, 1282, 1-23.
[ ] [PMID: 25720466]
Belouzard, S.; Millet, J.K.; Licitra, B.N.; Whittaker, G.R. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses, 2012, 4(6), 1011-1033.
[ ] [PMID: 22816037]
Madu, I.G.; Roth, S.L.; Belouzard, S.; Whittaker, G.R. Characterization of a highly conserved domain within the severe acute respiratory syndrome coronavirus spike protein S2 domain with characteristics of a viral fusion peptide. J. Virol., 2009, 83(15), 7411-7421.
[ ] [PMID: 19439480]
Lai, A.L.; Millet, J.K.; Daniel, S.; Freed, J.H.; Whittaker, G.R. The SARS-CoV fusion peptide forms an extended bipartite fusion platform that perturbs membrane order in a calcium-dependent manner. J. Mol. Biol., 2017, 429(24), 3875-3892.
[ ] [PMID: 29056462]
Schoeman, D.; Fielding, B.C. Coronavirus envelope protein: current knowledge. Virol. J., 2019, 16(1), 69.
[ ] [PMID: 31133031]
Chang, C.K.; Sue, S.C.; Yu, T.H.; Hsieh, C.M.; Tsai, C.K.; Chiang, Y.C.; Lee, S.J.; Hsiao, H.H.; Wu, W.J.; Chang, W.L.; Lin, C.H.; Huang, T.H. Modular organization of SARS coronavirus nucleocapsid protein. J. Biomed. Sci., 2006, 13(1), 59-72.
[ ] [PMID: 16228284]
Hurst, K.R.; Koetzner, C.A.; Masters, P.S. Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. J. Virol., 2009, 83(14), 7221-7234.
[ ] [PMID: 19420077]
Siu, Y.L.; Teoh, K.T.; Lo, J.; Chan, C.M.; Kien, F.; Escriou, N.; Tsao, S.W.; Nicholls, J.M.; Altmeyer, R.; Peiris, J.S.; Bruzzone, R.; Nal, B. The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles. J. Virol., 2008, 82(22), 11318-11330.
[ ] [PMID: 18753196]
J., Alsaadi E.A.; Jones, I.M. Membrane binding proteins of coronaviruses. Future Virol., 2019, 14(4), 275-286.
[ ] [PMID: 32201500]
Li, W.; Shi, Z.; Yu, M.; Ren, W.; Smith, C.; Epstein, J.H.; Wang, H.; Crameri, G.; Hu, Z.; Zhang, H.; Zhang, J.; McEachern, J.; Field, H.; Daszak, P.; Eaton, B.T.; Zhang, S.; Wang, L.F. Bats are natural reservoirs of SARS-like coronaviruses. Science, 2005, 310(5748), 676-679.
[ ] [PMID: 16195424]
Lau, S.K.; Woo, P.C.; Li, K.S.; Huang, Y.; Tsoi, H.W.; Wong, B.H.; Wong, S.S.; Leung, S.Y.; Chan, K.H.; Yuen, K.Y. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc. Natl. Acad. Sci. USA, 2005, 102(39), 14040-14045.
[ ] [PMID: 16169905]
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), 6134-6142.
[ ] [PMID: 15163706]
Li, W.; Moore, M.J.; Vasilieva, N.; Sui, J.; Wong, S.K.; Berne, M.A.; Somasundaran, M.; Sullivan, J.L.; Luzuriaga, K.; Greenough, T.C.; Choe, H.; Farzan, M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003, 426(6965), 450-454.
[ ] [PMID: 14647384]
Li, W.; Zhang, C.; Sui, J.; Kuhn, J.H.; Moore, M.J.; Luo, S.; Wong, S.K.; Huang, I.C.; Xu, K.; Vasilieva, N.; Murakami, A.; He, Y.; Marasco, W.A.; Guan, Y.; Choe, H.; Farzan, M. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J., 2005, 24(8), 1634-1643.
[ ] [PMID: 15791205]
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(6483), 1260-1263.
[ ] [PMID: 32075877]
Coutard, B.; Valle, C.; de Lamballerie, X.; Canard, B.; Seidah, N.G.; Decroly, E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res., 2020, 176, 104742
[ ] [PMID: 32057769]
Li, F. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J. Virol., 2015, 89(4), 1954-1964.
[ ] [PMID: 25428871]
Li, F. Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections. J. Virol., 2008, 82(14), 6984-6991.
[ ] [PMID: 18448527]
Li, F.; Li, W.; Farzan, M.; Harrison, S.C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 2005, 309(5742), 1864-1868.
[ ] [PMID: 16166518]
Wu, K.; Peng, G.; Wilken, M.; Geraghty, R.J.; Li, F. Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. J. Biol. Chem., 2012, 287(12), 8904-8911.
[ ] [PMID: 22291007]
Wan, Y.; Shang, J.; Graham, R.; Baric, R.S.; Li, F. Receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J. Virol., 2020, 94(7), 1-9.
[ ] [PMID: 31996437]
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, 181(2), 281-292.e6.
[ ] [PMID: 32155444]
Ziebuhr, J.; Snijder, E.J.; Gorbalenya, A.E. Virus-encoded proteinases and proteolytic processing in the Nidovirales. J. Gen. Virol., 2000, 81(Pt 4), 853-879.
[ ] [PMID: 10725411]
Xu, X.; Liu, Y.; Weiss, S.; Arnold, E.; Sarafianos, S.G.; Ding, J. Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design. Nucleic Acids Res., 2003, 31(24), 7117-7130.
[ ] [PMID: 14654687]
Li, F. Structure, function, and evolution of coronavirus spike proteins. Annu. Rev. Virol., 2016, 3(1), 237-261.
[ ] [PMID: 27578435]
Bosch, B.J.; van der Zee, R.; de Haan, C.A.; Rottier, P.J. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J. Virol., 2003, 77(16), 8801-8811.
[ ] [PMID: 12885899]
Walls, A.C.; Tortorici, M.A.; Snijder, J.; Xiong, X.; Bosch, B.J.; Rey, F.A.; Veesler, D. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl. Acad. Sci. USA, 2017, 114(42), 11157-11162.
[ ] [PMID: 29073020]
Gui, M.; Song, W.; Zhou, H.; Xu, J.; Chen, S.; Xiang, Y.; Wang, X. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res., 2017, 27(1), 119-129.
[ ] [PMID: 28008928]
Pallesen, J.; Wang, N.; Corbett, K.S.; Wrapp, D.; Kirchdoerfer, R.N.; Turner, H.L.; Cottrell, C.A.; Becker, M.M.; Wang, L.; Shi, W.; Kong, W.P.; Andres, E.L.; Kettenbach, A.N.; Denison, M.R.; Chappell, J.D.; Graham, B.S.; Ward, A.B.; McLellan, J.S. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl. Acad. Sci. USA, 2017, 114(35), E7348-E7357.
[ ] [PMID: 28807998]
Walls, A.C.; Xiong, X.; Park, Y-J.; Tortorici, M.A.; Snijder, J.; Quispe, J.; Cameroni, E.; Gopal, R.; Dai, M.; Lanzavecchia, A.; Zambon, M.; Rey, F.A.; Corti, D.; Veesler, D. Unexpected receptor functional mimicry elucidates activation of coronavirus fusion. Cell, 2019, 176(5), 1026-1039.
[ ] [PMID: 30712865]
Yuan, Y.; Cao, D.; Zhang, Y.; Ma, J.; Qi, J.; Wang, Q.; Lu, G.; Wu, Y.; Yan, J.; Shi, Y.; Zhang, X.; Gao, G.F. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat. Commun., 2017, 8, 15092.
[ ] [PMID: 28393837]
Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science, 2020, 367(6485), 1444-1448.
[ ] [PMID: 32132184]
Donoghue, M.; Hsieh, F.; Baronas, E.; Godbout, K.; Gosselin, M.; Stagliano, N.; Donovan, M.; Woolf, B.; Robison, K.; Jeyaseelan, R.; Breitbart, R.E.; Acton, S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res., 2000, 87(5), E1-E9.
[ ] [PMID: 10969042]
Zhang, H.; Wada, J.; Hida, K.; Tsuchiyama, Y.; Hiragushi, K.; Shikata, K.; Wang, H.; Lin, S.; Kanwar, Y.S.; Makino, H. Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys. J. Biol. Chem., 2001, 276(20), 17132-17139.
[ ] [PMID: 11278314]
Song, W.; Gui, M.; Wang, X.; Xiang, Y. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog., 2018, 14(8), e1007236
[ ] [PMID: 30102747]
Zhang, C.; Zheng, W.; Huang, X.; Bell, E.W.; Zhou, X.; Zhang, Y. Protein structure and sequence reanalysis of 2019-nCoV genome refutes snakes as its intermediate host and the unique similarity between its spike protein insertions and HIV-1. J. Proteome Res., 2020, 19(4), 1351-1360.
[ ] [PMID: 32200634]
Shang, J.; Wan, Y.; Luo, C.; Ye, G.; Geng, O.; Auerbach, A. Cell entry mechanisms of SARS-CoV-2. Proc. Natl. Acad. Sci. USA, 2020, 117(21), 11727-11734.
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[ ] [PMID: 32142651]
Ou, X.; Liu, Y.; Lei, X.; Li, P.; Mi, D.; Ren, L.; Guo, L.; Guo, R.; Chen, T.; Hu, J.; Xiang, Z.; Mu, Z.; Chen, X.; Chen, J.; Hu, K.; Jin, Q.; Wang, J.; Qian, Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun., 2020, 11(1), 1620.
[ ] [PMID: 32221306]
Du, L.; He, Y.; Zhou, Y.; Liu, S.; Zheng, B.J.; Jiang, S. The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat. Rev. Microbiol., 2009, 7(3), 226-236.
[ ] [PMID: 19198616]
Du, L.; Tai, W.; Yang, Y.; Zhao, G.; Zhu, Q.; Sun, S.; Liu, C.; Tao, X.; Tseng, C.K.; Perlman, S.; Jiang, S.; Zhou, Y.; Li, F. Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines. Nat. Commun., 2016, 7, 13473.
[ ] [PMID: 27874853]
Shang, J.; Ye, G.; Shi, K.; Wan, Y.; Luo, C.; Aihara, H.; Geng, Q.; Auerbach, A.; Li, F. Structural basis of receptor recognition by SARS-CoV-2. Nature, 2020, 581(7807), 221-224.
[ ] [PMID: 32225175]
Rahman, N.; Basharat, Z.; Yousuf, M.; Castaldo, G.; Rastrelli, L.; Khan, H. Virtual screening of natural products against type II transmembrane serine protease (TMPRSS2), the priming agent of coronavirus 2 (SARS-CoV-2). Molecules, 2020, 25(10), 2271.
[ ] [PMID: 32408547]
Iwata-Yoshikawa, N.; Okamura, T.; Shimizu, Y.; Hasegawa, H.; Takeda, M.; Nagata, N. TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J. Virol., 2019, 93(6), e01815-e01818.
[ ] [PMID: 30626688]
Fahmi, M.; Kubota, Y.; Ito, M. Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV. Infect. Genet. Evol., 2020, 81, 104272
[ ] [PMID: 32142938]
van der Hoeven, B.; Oudshoorn, D.; Koster, A.J.; Snijder, E.J.; Kikkert, M.; Bárcena, M. Biogenesis and architecture of arterivirus replication organelles. Virus Res., 2016, 220, 70-90.
[ ] [PMID: 27071852]
Oudshoorn, D.; Rijs, K.; Limpens, R.W.A.L.; Groen, K.; Koster, A.J.; Snijder, E.J.; Kikkert, M.; Bárcena, M. Expression and cleavage of middle east respiratory syndrome coronavirus nsp3-4 polyprotein induce the formation of double-membrane vesicles that mimic those associated with coronaviral RNA replication. MBio, 2017, 8(6), e01658-e17.
[ ] [PMID: 29162711]
Gordon, C.J.; Tchesnokov, E.P.; Woolner, E.; Perry, J.K.; Feng, J.Y.; Porter, D.P.; Gotte, M. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J. Biol. Chem., 2020, 295(15), 4773-4779.
[ ] [PMID: 32094225]
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., 2020, 30(3), 269-271.
[ ] [PMID: 32020029]
Gordon, C.J.; Tchesnokov, E.P.; Feng, J.Y.; Porter, D.P.; Götte, M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J. Biol. Chem., 2020, 295(15), 4773-4779.
[ ] [PMID: 32094225]
Sheahan, T.P.; Sims, A.C.; Graham, R.L.; Menachery, V.D.; Gralinski, L.E.; Case, J.B.; Leist, S.R.; Pyrc, K.; Feng, J.Y.; Trantcheva, I.; Bannister, R.; Park, Y.; Babusis, D.; Clarke, M.O.; Mackman, R.L.; Spahn, J.E.; Palmiotti, C.A.; Siegel, D.; Ray, A.S.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med., 2017, 9(396), eaal3653
[ ] [PMID: 28659436]
Sheahan, T.P.; Sims, A.C.; Leist, S.R.; Schäfer, A.; Won, J.; Brown, A.J.; Montgomery, S.A.; Hogg, A.; Babusis, D.; Clarke, M.O.; Spahn, J.E.; Bauer, L.; Sellers, S.; Porter, D.; Feng, J.Y.; Cihlar, T.; Jordan, R.; Denison, M.R.; Baric, R.S. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun., 2020, 11(1), 222.
[ ] [PMID: 31924756]
[63] Adaptive COVID-19 Treatment Trial (ACTT),; 2020.Available from: .
Gilead.Gilead announces results from phase 3 trial of investigational antiviral remdesivir in patients with severe COVID-19. Gilead Sciences , 2020.Available from: .
FDA. Letter of Authorization, EUA for Veklury (remdesivir).. Available from, 2020.
Hendaus, M.A. Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary. J. Biomol. Struct. Dyn., 2020. (in press)
[ ] [PMID: 32396771]
Babadaei, M.M.N.; Hasan, A.; Vahdani, Y.; Bloukh, S.H.; Sharifi, M.; Kachooei, E.; Haghighat, S.; Falahati, M. Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase. J. Biomol. Struct. Dyn., 2020, 1-9. (online ahead of print)
[] [PMID: 32397906]
Xu, J.; Shi, P-Y.; Li, H.; Zhou, J. Broad spectrum antiviral agent niclosamide and its therapeutic potential. ACS Infect. Dis., 2020, 6(5), 909-915.
[ ] [PMID: 32125140]
Mehra, M.R.; Desai, S.S.; Ruschitzka, F.; Patel, A.N. Hydroxychloroquine or chloroquine with or without amacrolide for treatment of COVID-19: a multinational registry analysis. The Lancet, 2020. (In Press)
Caly, L.; Druce, J.D.; Catton, M.G.; Jans, D.A.; Wagstaff, K.M. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res., 2020, 178, 104787
[ ] [PMID: 32251768]
González Canga, A.; Sahagún Prieto, A.M.; Diez Liébana, M.J.; Fernández Martínez, N.; Sierra Vega, M.; García Vieitez, J.J. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J., 2008, 10(1), 42-46.
[ ] [PMID: 18446504]
Sharun, K.; Dhama, K.; Patel, S.K.; Pathak, M.; Tiwari, R.; Singh, B.R.; Sah, R.; Bonilla-Aldana, D.K.; Rodriguez-Morales, A.J.; Leblebicioglu, H. Ivermectin, a new candidate therapeutic against SARS-CoV-2/COVID-19. Ann. Clin. Microbiol. Antimicrob., 2020, 19(1), 23.
[ ] [PMID: 32473642]
Schmith, V.D.; Zhou, J.; Lohmer, L.R.L. The approved dose of ivermectin alone is not the ideal dose for the treatment of COVID- 19. Clin. Pharmacol. Therap, 2020. (online ahead of print)
Patrì, A.; Fabbrocini, G. Hydroxychloroquine and ivermectin: A synergistic combination for COVID-19 chemoprophylaxis and treatment? J. Am. Acad. Dermatol., 2020, 82(6), e221
[ ] [PMID: 32283237]
Mori, M.; Capasso, C.; Carta, F.; William a Donald, W. A.; Supuran, C. T. A deadly spillover: SARS-CoV-2 outbreak. Expert Opin. Therap. Pat., 2020. (online ahead of print)
Yao, T-T.; Qian, J-D.; Zhu, W-Y.; Wang, Y.; Wang, G.Q. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J. Med. Virol., 2020, 92(6), 556-563.
[ ] [PMID: 32104907]
Lin, M.H.; Moses, D.C.; Hsieh, C.H.; Cheng, S.C.; Chen, Y.H.; Sun, C.Y.; Chou, C.Y. Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res., 2018, 150, 155-163.
[ ] [PMID: 29289665]
Li, G.; De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov., 2020, 19(3), 149-150.
[ ] [PMID: 32127666]
Liu, C.; Zhou, Q.; Li, Y.; Garner, L.V.; Watkins, S.P.; Carter, L.J.; Smoot, J.; Gregg, A.C.; Daniels, A.D.; Jervey, S.; Albaiu, D. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent. Sci., 2020, 6(3), 315-331.
[ ] [PMID: 32226821]
Dai, W.; Zhang, B.; Jiang, X-M.; Su, H.; Li, J.; Zhao, Y.; Xie, X.; Jin, Z.; Peng, J.; Liu, F.; Li, C.; Li, Y.; Bai, F.; Wang, H.; Cheng, X.; Cen, X.; Hu, S.; Yang, X.; Wang, J.; Liu, X.; Xiao, G.; Jiang, H.; Rao, Z.; Zhang, L.K.; Xu, Y.; Yang, H.; Liu, H. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 2020, 368(6497), 1331-1335.
[ ] [PMID: 32321856]
Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 2020, 368(6489), 409-412.
[ ] [PMID: 32198291]
Phuong, B.T.; My, T.T.A.; Hai, N.T.T. Investigation into SARS-CoV-2 resistance of compounds in garlic essential oil. ACS Omega, 2020, 5(14), 8312-8320.
Liu, J.; Cao, R.; Xu, M.; Wang, X.; Zhang, H.; Hu, H.; Li, Y.; Hu, Z.; Zhong, W.; Wang, M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov., 2020, 6, 16.
[ ] [PMID: 32194981]
Colson, P.; Rolain, J.M.; Raoult, D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int. J. Antimicrob. Agents, 2020, 55(3), 105923
[ ] [PMID: 32070753]
Jin, Z.; Du, X.; Xu, Y.; Deng, Y.; Liu, M. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature, 2019, 582, 289-293.
[ y ] [PMID: 32272481]
Batra, R.; Chan, H.; Kamath, G.; Ramprasad, R.; Cherukara, M.J.; Sankaranarayanan, S.K.R.S. Screening of therapeutic agents for COVID-19 using machine learning and ensemble docking studies. J. Phys. Chem. Lett., 2020, 11(17), 7058-7065.
[ ] [PMID: 32787328]
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(5), 305-306.
[ ] [PMID: 32273591]
Peel, M. Cost of vaccinating billions against COVID-19 put at more than $20Bn. 2020.Available from: .
Fast, E.; Altman, R.B.; Chen, B. Potential T-cell and B-cell epitopes of 2019-nCoV. bioRxiv, 2020.. (in press)
Kringelum, J.V.; Lundegaard, C.; Lund, O.; Nielsen, M. Reliable B cell epitope predictions: impacts of method development and improved benchmarking. PLOS Comput. Biol., 2012, 8(12), e1002829
[ ] [PMID: 23300419]
Tian, X.; Li, C.; Huang, A.; Xia, S.; Lu, S.; Shi, Z.; Lu, L.; Jiang, S.; Yang, Z.; Wu, Y.; Ying, T. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg. Microbes Infect., 2020, 9(1), 382-385.
[ ] [PMID: 32065055]
Takada, A.; Kawaoka, Y. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev. Med. Virol., 2003, 13(6), 387-398.
[ ] [PMID: 14625886]
Kam, Y.W.; Kien, F.; Roberts, A.; Cheung, Y.C.; Lamirande, E.W.; Vogel, L.; Chu, S.L.; Tse, J.; Guarner, J.; Zaki, S.R.; Subbarao, K.; Peiris, M.; Nal, B.; Altmeyer, R. Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcgammaRII-dependent entry into B cells in vitro. Vaccine, 2007, 25(4), 729-740.
[ ] [PMID: 17049691]
Tetro, J.A. Is COVID-19 receiving ADE from other coronaviruses? Microbes Infect., 2020, 22(2), 72-73.
[ ] [PMID: 32092539]
Lv, N.; Wu, N.C.; Tsang, O.T.Y.; Yuan, M.; Perera, R.A.P.M. Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections. bioRxiv, 2020.. (in press)
Negro, F. Is antibody-dependent enhancement playing a role in COVID-19 pathogenesis? Swiss Med. Wkly., 2020, 150, w20249
[ ] [PMID: 32298458]
Darrell, R.; Malone, R.W. Medical countermeasures analysis of 2019-nCoV and vaccine risks for antibody-dependent enhancement (ADE). Preprints, 2020, 2020, 030138
Duan, K.; Liu, B.; Li, C.; Zhang, H.; Yu, T.; Qu, J.; Zhou, M.; Chen, L.; Meng, S.; Hu, Y.; Peng, C.; Yuan, M.; Huang, J.; Wang, Z.; Yu, J.; Gao, X.; Wang, D.; Yu, X.; Li, L.; Zhang, J.; Wu, X.; Li, B.; Xu, Y.; Chen, W.; Peng, Y.; Hu, Y.; Lin, L.; Liu, X.; Huang, S.; Zhou, Z.; Zhang, L.; Wang, Y.; Zhang, Z.; Deng, K.; Xia, Z.; Gong, Q.; Zhang, W.; Zheng, X.; Liu, Y.; Yang, H.; Zhou, D.; Yu, D.; Hou, J.; Shi, Z.; Chen, S.; Chen, Z.; Zhang, X.; Yang, X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc. Natl. Acad. Sci. USA, 2020, 117(17), 9490-9496.
[ ] [PMID: 32253318]
Ariel, H. Thames, Kristy L. Wolniak, Samuel I. Stupp, and Michael C. Jewett. Principles Learned from the international race to develop a safe and effective COVID-19 vaccine. ACS Cent. Sci., 2020, 6(8), 1341-1347.
Wu, F.; Wang, A.; Liu, M.; Wang, Q.; Chen, J. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. Lancet Infect. Dis., 2020, 20, 352.
Zost, S.J.; Gilchuk, P.; Chen, R.E.; Case, J.B.; Reidy, J.X. Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Bioarxiv, 2020. (in press)
Rogers, T.F.; Zhao, F.; Huang, D.; Beutler, N.; Burns, A.; He, W.T.; Limbo, O.; Smith, C.; Song, G.; Woehl, J.; Yang, L.; Abbott, R.K.; Callaghan, S.; Garcia, E.; Hurtado, J.; Parren, M.; Peng, L.; Ricketts, J.; Ricciardi, M.J.; Rawlings, S.A.; Smith, D.M.; Nemazee, D.; Teijaro, J.R.; Voss, J.E.; Andrabi, R.; Briney, B.; Landais, E.; Sok, D.; Jardine, J.G.; Burton, D.R. Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model. bioRxiv, 2020., eabc7520
[ ] [PMID: 32511387]
Robbiani, D.F.; Gaebler, C.; Muecksch, F.; Lorenzi, J.C.C.; Wang, Z.; Cho, A.; Agudelo, M.; Barnes, C.O.; Gazumyan, A.; Finkin, S.; Hägglöf, T.; Oliveira, T.Y.; Viant, C.; Hurley, A.; Hoffmann, H.H.; Millard, K.G.; Kost, R.G.; Cipolla, M.; Gordon, K.; Bianchini, F.; Chen, S.T.; Ramos, V.; Patel, R.; Dizon, J.; Shimeliovich, I.; Mendoza, P.; Hartweger, H.; Nogueira, L.; Pack, M.; Horowitz, J.; Schmidt, F.; Weisblum, Y.; Michailidis, E.; Ashbrook, A.W.; Waltari, E.; Pak, J.E.; Huey-Tubman, K.E.; Koranda, N.; Hoffman, P.R.; West, A.P., Jr; Rice, C.M.; Hatziioannou, T.; Bjorkman, P.J.; Bieniasz, P.D.; Caskey, M.; Nussenzweig, M.C. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature, 2020, 584(7821), 437-442.
[ ] [PMID: 32555388]
Cheng, Y.; Wong, R.; Soo, Y.O.Y.; Wong, W.S.; Lee, C.K.; Ng, M.H.; Chan, P.; Wong, K.C.; Leung, C.B.; Cheng, G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur. J. Clin. Microbiol. Infect. Dis., 2005, 24(1), 44-46.
[ ] [PMID: 15616839]
Zhou, B.; Zhong, N.; Guan, Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N. Engl. J. Med., 2007, 357(14), 1450-1451.
[ ] [PMID: 17914053]
Hung, I.F.; To, K.K.W.; Lee, C-K.; Lee, K.L.; Chan, K.; Yan, W.W.; Liu, R.; Watt, C.L.; Chan, W.M.; Lai, K.Y.; Koo, C.K.; Buckley, T.; Chow, F.L.; Wong, K.K.; Chan, H.S.; Ching, C.K.; Tang, B.S.; Lau, C.C.; Li, I.W.; Liu, S.H.; Chan, K.H.; Lin, C.K.; Yuen, K.Y. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin. Infect. Dis., 2011, 52(4), 447-456.
[ ] [PMID: 21248066]
Ko, J-H.; Seok, H.; Cho, S.Y.; Ha, Y.E.; Baek, J.Y.; Kim, S.H.; Kim, Y.J.; Park, J.K.; Chung, C.R.; Kang, E.S.; Cho, D.; Müller, M.A.; Drosten, C.; Kang, C.I.; Chung, D.R.; Song, J.H.; Peck, K.R. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir. Ther. (Lond.), 2018, 23(7), 617-622.
[ ] [PMID: 29923831]
Van Beusekom, M. Autopsies of COVID-19 patients reveal clotting concerns. 2020.Available from: .
Gates, B. The first modern pandemic. The scientific advances we need to stop COVID-19. 2020.Available from: .
Liu, G.; Hong, T.; Yang, J. A single large dose of vitamin D could be used as a means of coronavirus disease 2019 prevention and treatment. Drug Des. Devel. Ther., 2020, 14, 3429-3434.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy