COVID-19 Repurposed Therapeutics Targeting the Viral Protease and Spike-protein:ACE2 Interface using MD-based Pharmacophore and Consensus Virtual Screening

08 May 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Molecular dynamics (MD) and enhanced sampling MD was performed for 100 ns on the biological assembly of the COVID-19 protease (6LU7), and a template of the COVID-19 S-protein:ACE2 receptor interface (99.88% coverage of 6M0J; model03, swissmodel). Apo-site pharmacophores of the resulting structural clusters were used to mine the FDA database (8700 compounds), and a multi-target library was developed from MD-based hits in high affinity sites across 100 ns. Consensus hits from high throughput docking in crystal structures 5R82, 6LU7 and 6Y2F (protease), and 6VW1 (S-protein:ACE2) were also added, and the resulting libraries were re-docked into MD sites to collect potential COVID-19 re-purposed therapeutics by estimated binding energies.

Keywords

nCov2019, nCov-2019, COVID2019, Drug Repurposing, Docking
molecular dynamics
docking simulation approaches
SARS-CoV-2 main protease
SARS-CoV-2 S-protein
pharmacophore analyses
virtual screening

Supplementary materials

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