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Title: Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure : virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates
Authors: Chen, YW 
Yiu, CPB
Wong, KY 
Issue Date: 2020
Source: F1000Research, 2020, v. 9, 129, p. 1-16
Abstract: We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL pro) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart.  With the 3CL pro molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache.  The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.
Keywords: 2019-nCoV
3C-like protease
Antiviral
Coronavirus
COVID-19
Drug repurpose
HCV
Hepatitis C virus
Ledipasvir
Molecular modelling
SARS
Velpatasvir
Virtual screening
Publisher: F1000 Research
Journal: F1000Research 
EISSN: 2046-1402
DOI: 10.12688/f1000research.22457.1
Rights: © 2020 Chen YW et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The following publication Chen YW, Yiu CPB and Wong KY. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CLpro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates [version 1; peer review: 3 approved]. F1000Research 2020, 9:129 is available at https://dx.doi.org/10.12688/f1000research.22457.1
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