Nursing

Gene

Coronavirus

Helicase

Virtual screening

Biology

Virology

Homology modeling

Biochemistry

RNA Helicase A

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Docking (animal)

Computational biology

Drug discovery

Coronavirus disease 2019 (COVID-19)

Genetics

Bioinformatics

Binding site

Enzyme

Infectious disease (medical specialty)

Medicine

Chemistry

Pandemic

Disease

Pathology

The Journal of Physical Chemistry Letters

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.

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