Discovery of COVID-19 Inhibitors Targeting the SARS-CoV-2 Nsp13 Helicase

Mark Andrew White, Wei Lin, Xiaodong Cheng

Research output: Contribution to journalArticlepeer-review

Abstract

The raging COVID-19 pandemic caused by SARS-CoV-2 has infected tens of millions of people and killed several hundred thousand patients worldwide. Currently, there are no effective drugs or vaccines available for treating coronavirus infections. In this study, we have focused on the SARS-CoV-2 helicase (Nsp13), which is critical for viral replication and the most conserved nonstructural protein within the coronavirus family. Using homology modeling that couples published electron-density with molecular dynamics (MD)-based structural refinements, we generated structural models of the SARS-CoV-2 helicase in its apo- and ATP/RNA-bound conformations. We performed virtual screening of ∼970 »000 chemical compounds against the ATP-binding site to identify potential inhibitors. Herein, we report docking hits of approved human drugs targeting the ATP-binding site. Importantly, two of our top drug hits have significant activity in inhibiting purified recombinant SARS-CoV-2 helicase, providing hope that these drugs can be potentially repurposed for the treatment of COVID-19.

Original languageEnglish (US)
Pages (from-to)9144-9151
Number of pages8
JournalJournal of Physical Chemistry Letters
DOIs
StateAccepted/In press - 2020

ASJC Scopus subject areas

  • Materials Science(all)
  • Physical and Theoretical Chemistry

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