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

•The MT-DTI deep learning model was used to identify potent drugs for SARS-CoV-2.•Atazanavir, remdesivir, and Kaletra were predicted to inhibit SARS-CoV-2.•Rapamycin and tiotropium bromide may also be effective for SARS-CoV-2. The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2)...

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Published in:Computational and structural biotechnology journal Vol. 18; pp. 784 - 790
Main Authors: Beck, Bo Ram, Shin, Bonggun, Choi, Yoonjung, Park, Sungsoo, Kang, Keunsoo
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.01.2020
Research Network of Computational and Structural Biotechnology
Elsevier
Subjects:
antiretroviral agents
Atazanavir
chemical compounds
China
Communications
Coronavirus
COVID-19
Deep learning
Drug repurposing
drug therapy
drugs
Human immunodeficiency virus
MT-DTI
Orthocoronavirinae
prediction
proteinases
SARS-CoV-2
viral proteins
China
COVID-19
Deep learning
SARS-CoV-2
Coronavirus
Atazanavir
Drug repurposing
MT-DTI
ISSN:2001-0370, 2001-0370
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Summary:•The MT-DTI deep learning model was used to identify potent drugs for SARS-CoV-2.•Atazanavir, remdesivir, and Kaletra were predicted to inhibit SARS-CoV-2.•Rapamycin and tiotropium bromide may also be effective for SARS-CoV-2. 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.
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ISSN:2001-0370
2001-0370
DOI:10.1016/j.csbj.2020.03.025