Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs

Sangeun Jeon, Meehyun Ko, Jihye Lee, Inhee Choi, Soo Young Byun, Soonju Park, David Shum, Seungtaek Kim, Sangeun Jeon, Meehyun Ko, Jihye Lee, Inhee Choi, Soo Young Byun, Soonju Park, David Shum, Seungtaek Kim

Abstract

Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs-niclosamide and ciclesonide-were notable in some respects.

Keywords: COVID-19; FDA-approved drug; SARS-CoV-2.

Copyright © 2020 American Society for Microbiology.

Figures

FIG 1
FIG 1
(A) Dose-response curve analysis by immunofluorescence for reference drugs. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). The confocal microscope images show cell nuclei (red) and viral N protein (green) at each drug concentration. Means ± SD were calculated from duplicate experiments. (B) Dose-response curve analysis by immunofluorescence for 45 drugs that were tested in this study. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). Means ± SD were calculated from duplicate experiments.
FIG 1
FIG 1
(A) Dose-response curve analysis by immunofluorescence for reference drugs. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). The confocal microscope images show cell nuclei (red) and viral N protein (green) at each drug concentration. Means ± SD were calculated from duplicate experiments. (B) Dose-response curve analysis by immunofluorescence for 45 drugs that were tested in this study. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). Means ± SD were calculated from duplicate experiments.
FIG 1
FIG 1
(A) Dose-response curve analysis by immunofluorescence for reference drugs. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). The confocal microscope images show cell nuclei (red) and viral N protein (green) at each drug concentration. Means ± SD were calculated from duplicate experiments. (B) Dose-response curve analysis by immunofluorescence for 45 drugs that were tested in this study. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). Means ± SD were calculated from duplicate experiments.
FIG 1
FIG 1
(A) Dose-response curve analysis by immunofluorescence for reference drugs. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). The confocal microscope images show cell nuclei (red) and viral N protein (green) at each drug concentration. Means ± SD were calculated from duplicate experiments. (B) Dose-response curve analysis by immunofluorescence for 45 drugs that were tested in this study. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). Means ± SD were calculated from duplicate experiments.
FIG 2
FIG 2
Dose-response curve analysis by cytopathic effect. The blue squares represent inhibition of SARS-CoV-2 infection (%), and the red triangles represent cell viability (%). Means ± SD were calculated from duplicate experiments.

References

    1. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, Chen H-D, Chen J, Luo Y, Guo H, Jiang R-D, Liu M-Q, Chen Y, Shen X-R, Wang X, Zheng X-S, Zhao K, Chen Q-J, Deng F, Liu L-L, Yan B, Zhan F-X, Wang Y-Y, Xiao G-F, Shi Z-L. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270–273. doi:10.1038/s41586-020-2012-7.
    1. Mizumoto K, Chowell G. 2020. Estimating the risk of 2019 novel coronavirus death during the course of the outbreak in China, 2020. medRxiv doi:10.1101/2020.02.19.20025163.
    1. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY, 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 TTY, Wu JT, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z. 2020. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 382:1199–1207. doi:10.1056/NEJMoa2001316.
    1. Ashburn TT, Thor KB. 2004. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 3:673–683. doi:10.1038/nrd1468.
    1. Maxmen A. 2020. More than 80 clinical trials launch to test coronavirus treatments. Nature 578:347–348. doi:10.1038/d41586-020-00444-3.
    1. 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. doi:10.1038/s41422-020-0282-0.
    1. Xu J, Shi P-Y, Li H, Zhou J. 2020. Broad spectrum antiviral agent niclosamide and its therapeutic potential. ACS Infect Dis doi:10.1021/acsinfecdis.0c00052.
    1. Wu C-J, Jan J-T, Chen C-M, Hsieh H-P, Hwang D-R, Liu H-W, Liu C-Y, Huang H-W, Chen S-C, Hong C-F, Lin R-K, Chao Y-S, Hsu J. 2004. Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrob Agents Chemother 48:2693–2696. doi:10.1128/AAC.48.7.2693-2696.2004.
    1. Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A, Hafner K, Papies J, Mösbauer K, Zellner A, Zannas AS, Herrmann A, Holsboer F, Brack-Werner R, Boshart M, Müller-Myhsok B, Drosten C, Müller MA, Rein T. 2019. SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-coronavirus infection. Nat Commun 10:5770. doi:10.1038/s41467-019-13659-4.
    1. Smith TC, Kinkel AW, Gryczko CM, Goulet JR. 1976. Absorption of pyrvinium pamoate. Clin Pharmacol Ther 19:802–806. doi:10.1002/cpt1976196802.
    1. Schaffner TJ, Skoner DP. 2009. Ciclesonide: a safe and effective inhaled corticosteroid for the treatment of asthma. J Asthma Allergy 2:25–32. doi:10.2147/jaa.s4651.
    1. Matsuyama S, Kawase M, Nao N, Shirato K, Ujike M, Kamitani W, Shimojima M, Fukushi S. 2020. The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15. bioRxiv. doi:10.1101/2020.03.11.987016.
    1. Iwabuchi K, Yoshie K, Kurakami Y, Takahashi K, Kato Y, Morishima T. 2020. Therapeutic potential of ciclesonide inhalation for COVID-19 pneumonia: report of three cases. J Infect Chemother 26:625–632. doi:10.1016/j.jiac.2020.04.007.
    1. Beck BR, Shin B, Choi Y, Park S, Kang K. 2020. Predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-nCoV), Wuhan, China through a drug-target interaction deep learning model. bioRxiv. doi:10.1101/2020.01.31.929547.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir