Citation: Danrong Shi, Keda Chen, Xiangyun Lu, Linfang Cheng, Tianhao Weng, Fumin Liu, Nanping Wu, Lanjuan Li, Hangping Yao. Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro .VIROLOGICA SINICA, 2022, 37(2) : 295-298.  http://dx.doi.org/10.1016/j.virs.2022.01.031

Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro

  • Highlights
    1) A comprehensive evaluation method for anti-SARS-CoV-2 drugs was established based on RT-qPCR, TCID50 method, and immunofluorescence.
    2) A significant antiviral effect of rHuIFN-α1b was shown with EC50=0.12 IU/mL in Vero cells and EC50=0.52 IU/mL in Calu-3 cells, which was better than rHuIFN-α2b (EC50=0.25 IU/mL in Vero cells and EC50=2.48 IU/mL in Calu-3 cells).
    3) rHuIFN-α1b has a good potential in the application of anti-COVID-19 therapy.

  • 加载中
  • 10.1016j.virs.2022.01.031-ESM.docx
    1. 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.

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

    3. 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.

    4. 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).

    5. 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.

    6. 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.

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

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

    9. 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.

    10. 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.

    11. 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).

    12. 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).

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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.

    21. 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.

    22. 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.

    23. 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.

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

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

    26. 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.

    27. 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.

    28. 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.

    29. 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.

    30. 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.

    31. 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.

    32. 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.

    33. 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.

    34. 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.

  • 加载中

Article Metrics

Article views(4823) PDF downloads(12) Cited by()

Related
Proportional views

    Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro

      Corresponding author: Nanping Wu, flwnp2013@163.com
      Corresponding author: Lanjuan Li, ljli@zju.edu.cn
      Corresponding author: Hangping Yao, yaohangping@zju.edu.cn
    • a State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
    • b Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, China

    Abstract: Highlights
    1) A comprehensive evaluation method for anti-SARS-CoV-2 drugs was established based on RT-qPCR, TCID50 method, and immunofluorescence.
    2) A significant antiviral effect of rHuIFN-α1b was shown with EC50=0.12 IU/mL in Vero cells and EC50=0.52 IU/mL in Calu-3 cells, which was better than rHuIFN-α2b (EC50=0.25 IU/mL in Vero cells and EC50=2.48 IU/mL in Calu-3 cells).
    3) rHuIFN-α1b has a good potential in the application of anti-COVID-19 therapy.

    Reference (34)

    目录

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return