Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CLpro) structure: Virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates

Yu Wai Chen (Corresponding Author), Chin Pang Bennu Yiu, Kwok Yin Wong (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

181 Citations (Scopus)

Abstract

We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CLpro) 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 3CLpro 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.

Original languageEnglish
Article number129
JournalF1000Research
Volume9
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • 2019-nCoV
  • 3C-like protease
  • Antiviral
  • Coronavirus
  • COVID-19
  • Drug repurpose
  • HCV
  • Hepatitis C virus
  • Ledipasvir
  • Molecular modelling
  • SARS
  • Velpatasvir
  • Virtual screening

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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