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. 2020 Mar 30:18:784-790.
doi: 10.1016/j.csbj.2020.03.025. eCollection 2020.

Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model

Bo Ram Beck  1 , Bonggun Shin  1   2 , Yoonjung Choi  1 , Sungsoo Park  1 , Keunsoo Kang  3
Affiliations

Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model

Bo Ram Beck et al. Comput Struct Biotechnol J. .

Abstract

The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.

Keywords: Atazanavir; COVID-19; Coronavirus; Deep learning; Drug repurposing; MT-DTI; SARS-CoV-2.

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Conflict of interest statement

Beck B.R., Choi Y., and Park S. are employed by company Deargen Inc. Shin B. is employed by Deargen Inc as a part-time advisor. Kang K. is one of the co-founders of, and a shareholder in, Deargen Inc.

Figures

Fig. 1
Fig. 1
Comparison of MT-DTI and AutoDock Vina results. 60 known FDA-approved antiviral drugs (left) and 3410 FDA-approved drugs (right) were evaluated by means of the MT-DTI deep learning-based affinity score (higher is better), and AutoDock Vina docking score (lower is better). Remdesivir, which is not an FDA-approved drug, but regarded as a promising antiviral drug for SARS-CoV-2, was included in this analysis.
See this image and copyright information in PMC

References

    1. Cavanagh D. Coronavirus avian infectious bronchitis virus. Vet Res. 2007;38:281–297. - PubMed
    1. Lim Y.X., Ng Y.L., Tam J.P., Liu D.X. Human coronaviruses: a review of virus-host interactions. Diseases. 2016;4(3) - PMC - PubMed
    1. Weiss S.R., Leibowitz J.L. Coronavirus pathogenesis. Adv Virus Res. 2011;81:85–164. - PMC - PubMed
    1. Woo P.C., Huang Y., Lau S.K., Yuen K.Y. Coronavirus genomics and bioinformatics analysis. Viruses. 2010;2:1804–1820. - PMC - PubMed
    1. Kuiken T., Fouchier R.A., Schutten M., Rimmelzwaan G.F., van Amerongen G., van Riel D., et al. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003;362:263–270. - PMC - PubMed