Predicting commercially available antiviral drugs that may act on the novel coronavirus (2019-nCoV), Wuhan, China through a drug-target interaction de

Bo Ram Beck, Bonggun Shin, Yoonjung Choi, Sungsoo Park, Keunsoo Kang

10.1101/2020.01.31.929547

Research curated

Abstract

The infection of a novel coronavirus found in Wuhan of China (2019-nCoV) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for 2019-nCoV, various strategies are being tested in China, including drug repurposing. In this study, we used our pretrained 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 2019-nCoV. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by 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 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for 2019-nCoV.

Source: BioRxiv

Related molecules

Name	Synonyms	Genes
Efavirenz
Ganciclovir
Acyclovir
Entecavir
Lomibuvir	VX-222, Lomibuvir, 1026785-59-0, 1026785-55-6, VX-222 (VCH-222, Lomibuvir)
Penciclovir
Trifluridine
Uridylate-specific endoribonuclease	NSP15, Non-structural protein 15, Nonstructural protein 15, NendoU, endoRNAse	rep, ORF1a-1b
Putative 2'-O-methyl transferase	2’-O-Ribose methyltransferase, Non-structural protein 16, Nonstructural protein 16, nsp16	rep, ORF1a-1b
Helicase	Helicase, nsp13, Hel, p66, p66-HEL, Non-structural protein 13	rep, ORF1a-1b
Exoribonuclease	ExoN, Non-structural protein14, Nonstructural protein14, nsp14, 5‘-to-3‘ exonuclease	rep, ORF1a-1b
Etravirine
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
Asunaprevir
Abacavir
Saquinavir
Boceprevir	Victrelis
Raltegravir
Nelfinavir
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Lamivudine
Grazoprevir	Grazoprevir,1350514-68-9,MK5172,UNII-8YE81R1X1J, MK 5172
Dolutegravir
Daclatasvir
Simeprevir	Olysio, TMC435350, TMC-435, TMC435
Danoprevir
Atazanavir
Ritonavir
Darunavir
Telaprevir
Lopinavir
Indinavir

Related interactions

Target	Drug	Type	Result
Exoribonuclease	Asunaprevir	Computational	positive
Helicase	Asunaprevir	Computational	positive
RNA dependent RNA polymerase	Asunaprevir	Computational	positive
Putative 2'-O-methyl transferase	Atazanavir	Computational	positive
Uridylate-specific endoribonuclease	Atazanavir	Computational	positive
Exoribonuclease	Atazanavir	Computational	positive
Helicase	Atazanavir	Computational	positive
Uridylate-specific endoribonuclease	Nelfinavir	Computational	positive
Helicase	Nelfinavir	Computational	positive
Uridylate-specific endoribonuclease	Darunavir	Computational	positive
Exoribonuclease	Darunavir	Computational	positive
Helicase	Darunavir	Computational	positive
RNA dependent RNA polymerase	Abacavir	Computational	positive
RNA dependent RNA polymerase	Atazanavir	Computational	positive
RNA dependent RNA polymerase	Saquinavir	Computational	positive
3C-like protease	Asunaprevir	Computational	positive
RNA dependent RNA polymerase	Grazoprevir	Computational	positive
RNA dependent RNA polymerase	Daclatasvir	Computational	positive
Putative 2'-O-methyl transferase	Boceprevir	Computational	positive
Putative 2'-O-methyl transferase	Efavirenz	Computational	positive
Uridylate-specific endoribonuclease	Boceprevir	Computational	positive
Uridylate-specific endoribonuclease	Raltegravir	Computational	positive
Uridylate-specific endoribonuclease	Abacavir	Computational	positive
Uridylate-specific endoribonuclease	Telaprevir	Computational	positive
Uridylate-specific endoribonuclease	Lopinavir	Computational	positive
Uridylate-specific endoribonuclease	Lomibuvir	Computational	positive
Uridylate-specific endoribonuclease	Dolutegravir	Computational	positive
Uridylate-specific endoribonuclease	Grazoprevir	Computational	positive
Uridylate-specific endoribonuclease	Danoprevir	Computational	positive
Uridylate-specific endoribonuclease	Ritonavir	Computational	positive
Uridylate-specific endoribonuclease	Efavirenz	Computational	positive
Exoribonuclease	Lopinavir	Computational	positive
Exoribonuclease	Dolutegravir	Computational	positive
Exoribonuclease	Raltegravir	Computational	positive
Exoribonuclease	Lomibuvir	Computational	positive
Exoribonuclease	Ritonavir	Computational	positive
Exoribonuclease	Grazoprevir	Computational	positive
Exoribonuclease	Daclatasvir	Computational	positive
Exoribonuclease	Entecavir	Computational	positive
Exoribonuclease	Penciclovir	Computational	positive
Exoribonuclease	Ganciclovir	Computational	positive
Exoribonuclease	Danoprevir	Computational	positive
Exoribonuclease	Efavirenz	Computational	positive
Exoribonuclease	Simeprevir	Computational	positive
Helicase	Lomibuvir	Computational	positive
Helicase	Boceprevir	Computational	positive
Helicase	Entecavir	Computational	positive
Helicase	Efavirenz	Computational	positive
Helicase	Indinavir	Computational	positive
Helicase	Dolutegravir	Computational	positive
Helicase	Raltegravir	Computational	positive
Helicase	Etravirine	Computational	positive
Helicase	Penciclovir	Computational	positive
Helicase	Ganciclovir	Computational	positive
Helicase	Lopinavir	Computational	positive
Helicase	Ritonavir	Computational	positive
Helicase	Telaprevir	Computational	positive
Helicase	Grazoprevir	Computational	positive
Helicase	Simeprevir	Computational	positive
RNA dependent RNA polymerase	Lamivudine	Computational	positive
RNA dependent RNA polymerase	Ritonavir	Computational	positive
RNA dependent RNA polymerase	Danoprevir	Computational	positive
RNA dependent RNA polymerase	Trifluridine	Computational	positive
RNA dependent RNA polymerase	Penciclovir	Computational	positive
RNA dependent RNA polymerase	Lomibuvir	Computational	positive
RNA dependent RNA polymerase	Dolutegravir	Computational	positive
RNA dependent RNA polymerase	Entecavir	Computational	positive
RNA dependent RNA polymerase	Etravirine	Computational	positive
RNA dependent RNA polymerase	Acyclovir	Computational	positive
RNA dependent RNA polymerase	Ganciclovir	Computational	positive
3C-like protease	Dolutegravir	Computational	positive
3C-like protease	Efavirenz	Computational	positive
3C-like protease	Simeprevir	Computational	positive
3C-like protease	Atazanavir	Computational	positive
3C-like protease	Ritonavir	Computational	positive
RNA dependent RNA polymerase	Raltegravir	Computational	positive