• Ader, F., Peiffer-Smadja, N., Poissy, J., Bouscambert-Duchamp, M., Belhadi, D., Diallo, A., Delmas, C., Saillard, J., Dechanet, A., Mercier, N., Dupont, A., Alfaiate, T., Lescure, F.X., Raffi, F., Goehringer, F., Kimmoun, A., Jaureguiberry, S., Reignier, J., Nseir, S., Danion, F., Clere-Jehl, R., Bouiller, K., Navellou, J.C., Tolsma, V., Cabié, A., Dubost, C., Courjon, J., Leroy, S., Mootien, J., Gaci, R., Mourvillier, B., Faure, E., Pourcher, V., Gallien, S., Launay, O., Lacombe, K., Lanoix, J.P., Makinson, A., MartinBlondel, G., Bouadma, L., Botelho-Nevers, E., Gagneux-Brunon, A., Epaulard, O., Piroth, L., Wallet, F., Richard, J.C., Reuter, J., Staub, T., Lina, B., Noret, M., Andrejak, C., Lê, M.P., Peytavin, G., Hites, M., Costagliola, D., Yazdanpanah, Y., Burdet, C., Mentré, F., DisCoVeRy study group, 2021. An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19. Clin. Microbiol. Infect. 27, 1826–1837.

  • Al-Badr, A.A., Ajarim, T.D.S., 2018. Ganciclovir. Profiles Drug Subst. Excip. Relat. Methodol. 43, 1–208.

  • Cao, Y.C., Deng, Q.X., Dai, S.X., 2020. Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: an evaluation of the evidence. Trav. Med. Infect. Dis. 35, 101647.

  • Centers for Disease Control and Prevention (CDC), 2021. COVID-19: SARS-CoV-2 Variant Classifications and Definitions. US Department of Health and Human Services, CDC, Atlanta, GA. Available: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html. (Accessed 1 December 2021).

  • Chen, L., Shi, M., Deng, Q., Liu, W., Li, Q., Ye, P., Yu, X., Zhang, B., Xu, Y., Li, X., Yang, Y., Li, M., Yan, Y., Xu, Z., Yu, J., Xiang, L., Tang, X., Wan, G., Cai, Q., Wang, L., Hu, B., Xie, L., Li, G., Xie, L., Liu, X., Liu, C., Li, L., Chen, L., Jiang, X., Huang, Y., Wang, S., Guo, J., Shi, Y., Li, L., Wang, X., Zhao, Z., Li, Y., Liu, Y., Fu, Q., Zeng, Y., Zou, Y., Liu, D., Wan, D., Ai, T., Liu, H., 2020. A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon alpha1b nebulization. PLoS One 15, e0228391.

  • Choy, K.T., Wong, A.Y., Kaewpreedee, P., Sia, S.F., Chen, D., Hui, K.P.Y., Chu, D.K.W., Chan, M.C.W., Cheung, P.P., Huang, X., Peiris, M., Yen, H.L., 2020. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antivir. Res. 178, 104786.

  • Cinatl, J., Morgenstern, B., Bauer, G., Chandra, P., Rabenau, H., Doerr, H.W., 2003. Treatment of SARS with human interferons. Lancet 362, 293–294.

  • Dahl, H., Linde, A., Strannegård, Ö., 2009. In vitro inhibition of SARS virus replication by human interferons. Scand. J. Infect. Dis. 36, 829–831.

  • de Wilde, A.H., Raj, V.S., Oudshoorn, D., Bestebroer, T.M., van Nieuwkoop, S., Limpens, R.W.A.L., Posthuma, C.C., van der Meer, Y., Bárcena, M., Haagmans, B.L., Snijder, E.J., van den Hoogen, B.G., 2013. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferonalpha treatment. J. Gen. Virol. 94, 1749–1760.

  • Felgenhauer, U., Schoen, A., Gad, H.H., Hartmann, R., Schaubmar, A.R., Failing, K., Drosten, C., Weber, F., 2020. Inhibition of SARS–CoV-2 by type I and type III interferons. J. Biol. Chem. 295, 13958–13964.

  • Gilead, 2021a. Gilead statement on Veklury® (Remdesivir) and the SARS-CoV-2 omicron variant. Available: https://www.gilead.com/news-and-press/company-statements/gilead-statement-on-veklury-remdesivir-and-the-sars-cov-2-omicron-variant.(Accessed 1 December 2021).

  • Gilead, 2021b. Gilead's Veklury® (Remdesivir) associated with a reduction in mortality rate in hospitalized patients with COVID-19 across three analyses of large retrospective real-world data sets. Available: https://www.gilead.com/news-andpress/press-room/press-releases/2021/6/gileads-veklury-remdesivir-associatedwith-a-reduction-in-mortality-rate-in-hospitalized-patients-with-covid19-a cross-three-analyses-of-large-ret. (Accessed 1 December 2021).

  • Gobeil, S.M., Janowska, K., McDowell, S., Mansouri, K., Parks, R., Manne, K., Stalls, V., Kopp, M.F., Henderson, R., Edwards, R.J., Haynes, B.F., Acharya, P., 2020. D614G mutation alters SARS-CoV-2 spike conformation and enhances protease cleavage at the S1/S2 junction. Cell Rep. 34, 108630.

  • Grein, J., Ohmagari, N., Shin, D., Diaz, G., Asperges, E., Castagna, A., Feldt, T., Green, G., Green, M.L., Lescure, F.X., Nicastri, E., Oda, R., Yo, K., QuirosRoldan, E., Studemeister, A., Redinski, J., Ahmed, S., Bernett, J., Chelliah, D., Chen, D., Chihara, S., Cohen, S.H., Cunningham, J., D’Arminio Monforte, A., Ismail, S., Kato, H., Lapadula, G., L’Her, E., Maeno, T., Majumder, S., Massari, M., Mora-Rillo, M., Mutoh, Y., Nguyen, D., Verweij, E., Zoufaly, A., Osinusi, A.O., DeZure, A., Zhao, Y., Zhong, L., Chokkalingam, A., Elboudwarej, E., Telep, L., Timbs, L., Henne, I., Sellers, S., Cao, H., Tan, S.K., Winterbourne, L., Desai, P., Mera, R., Gaggar, A., Myers, R.P., Brainard, D.M., Childs, R., Flanigan, T., 2020. Compassionate use of remdesivir for patients with severe covid-19. N. Engl. J. Med. 382, 2327–2336.

  • Hawkins, M.J., Borden, E.C., Merritt, J.A., Edwards, B.S., Ball, L.A., Grossbard, E., Simon, K.J., 1984. Comparison of the biologic effects of two recombinant human interferons alpha (rA and rD) in humans. J. Clin. Oncol. 2, 221–226.

  • Huang, Y.Q., Tang, S.Q., Xu, X.L., Zeng, Y.M., He, X.Q., Li, Y., Harypursat, V., Lu, Y.Q., Wan, Y., Zhang, L., Sun, Q.Z., Sun, N.N., Wang, G.X., Yang, Z.P., Chen, Y.K., 2020. No statistically apparent difference in antiviral effectiveness observed among ribavirin plus interferon-alpha, lopinavir/ritonavir plus interferon-alpha, and ribavirin plus lopinavir/ritonavir plus interferon-alpha in patients with mild to moderate coronavirus disease 2019: results of a randomized, open-labeled prospective study. Front. Pharmacol. 11, 1071.

  • Huang, X., Zhang, X., Wang, F., Wei, H., Ma, H., Sui, M., Lu, J., Wang, H., Dumler, J.S., Sheng, G., Xu, B., 2016. Clinical efficacy of therapy with recombinant human interferon alpha1b in hand, foot, and mouth disease with enterovirus 71 infection. PLoS One 11, e0148907.

  • Leung, K., Shum, M.H., Leung, G.M., Lam, T.T., Wu, J.T., 2021. Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020. Euro Surveill. 26, 2002106.

  • Li, M.F., Jin, Q., Hu, G., Guo, H.Y., Hou, Y.D., 1992. A novel variant of human interferon alpha 1 gene. Sci. China E B 35, 200–206.

  • Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., Wang, Y., 2020. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 182, 1284–1294 e9.

  • Li, Q.Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., Ren, R., Leung, K.S.M., Lau, E.H.Y., Wong, J.Y., Xing, X., Xiang, N., Wu, Y., Li, C., Chen, Q., Li, D., Liu, T., Zhao, J., Liu, M., Tu, W., Chen, C., Jin, L., Yang, R., Wang, Q., Zhou, S., Wang, R., Liu, H., Luo, Y., Liu, Y., Shao, G., Li, H., Tao, Z., Yang, Y., Deng, Z., Liu, B., Ma, Z., Zhang, Y., Shi, G., Lam, T.T.Y., Wu, J.T., Gao, G.F., Cowling, B.J., Yang, B., Leung, G.M., Feng, Z., 2020. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N. Engl. J. Med. 382, 1199–1207.

  • Loutfy, M.R., Blatt, L.M., Siminovitch, K.A., Ward, S., Wolff, B., Lho, H., Pham, D.H., Deif, H., LaMere, E.A., Chang, M., Kain, K.C., Farcas, G.A., Ferguson, P., Latchford, M., Levy, G., Dennis, J.W., Lai, E.K., Fish, E.N., 2003. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA 290, 3222–3228.

  • Pandit, A., Bhalani, N., Bhushan, B.L.S., Koradia, P., Gargiya, S., Bhomia, V., Kansagra, K., 2021. Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: a phase II, randomized, controlled, open-label study. Int. J. Infect. Dis. 105, 516–521.

  • Reed, L.J., Muench, H., 1938. A simple method of estimating fifty per cent endpoints. Am. J. Epidemiol. 3, 493–497.

  • Sadler, A.J., Williams, B.R.G., 2008. Interferon-inducible antiviral effectors. Nat. Rev. Immunol. 8, 559–568.

  • Sainz, B., Mossel, E.C., Peters, C.J., Garry, R.F., 2004. Interferon-beta and interferongamma synergistically inhibit the replication of severe acute respiratory syndromeassociated coronavirus (SARS-CoV). Virology 329, 11–17.

  • Seidel, V., Feiterna-Sperling, C., Siedentopf, J.P., Hofmann, J., Henrich, W., Buhrer, C., Weizsacker, K., 2017. Intrauterine therapy of cytomegalovirus infection with valganciclovir: review of the literature. Med. Microbiol. Immunol. 206, 347–354.

  • 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., 2020. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun. 11, 222.

  • Vanderheiden, A., Ralfs, P., Chirkova, T., Upadhyay, A.A., Zimmerman, M.G., Bedoya, S., Aoued, H., Tharp, G.M., Pellegrini, K.L., Manfredi, C., Sorscher, E., Mainou, B., Lobby, J.L., Kohlmeier, J.E., Lowen, A.C., Shi, P.Y., Menachery, V.D., Anderson, L.J., Grakoui, A., Bosinger, S.E., Suthar, M.S., 2020. Type I and type III interferons restrict SARS-CoV-2 infection of human airway epithelial cultures. J. Virol. 94 e00985-20.

  • Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., Shi, Z., Hu, Z., Zhong, W., Xiao, G., 2020. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30, 269–271.

  • Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J.C., Muecksch, F., Rutkowska, M., Hoffmann, H.H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C.D., Caskey, M., Robbiani, D.F., Rice, C.M., Nussenzweig, M.C., Hatziioannou, T., Bieniasz, P.D., 2020. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife 9, e61312.

  • Wu, J.T., Leung, K., Leung, G.M., 2020. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 395, 689–697.

  • Zhang, L., Jackson, C.B., Mou, H., Ojha, A., Peng, H., Quinlan, B.D., Rangarajan, E.S., Pan, A., Vanderheiden, A., Suthar, M.S., Li, W., Izard, T., Rader, C., Farzan, M., Choe, H., 2020. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat. Commun. 11, 6013.

  • Zumla, A., Chan, J.F.W., Azhar, E.I., Hui, D.S.C., Yuen, K.Y., 2016. Coronaviruses - drug discovery and therapeutic options. Nat. Rev. Drug Discov. 15, 327–347.