Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay

• DOI: 10.1073/pnas.2024302118
• Publication Date: 2021-07-07T19:32:35Z
• Authors: Woo Dae Jang; Sangeun Jeon; Seungtaek Kim; Sang Yup Lee
• Keywords: 0301 basic medicine; 0303 health sciences; Alanine; Drug Evaluation, Preclinical; Drug Repositioning; Drug Synergism; Biological Sciences; Antiviral Agents; Adenosine Monophosphate; COVID-19 Drug Treatment; 3. Good health; User-Computer Interface; 03 medical and health sciences; Chlorocebus aethiops; Animals; Humans; Vero Cells

Significance Recent spread of SARS-CoV-2 has sparked significant health concerns of emerging infectious viruses. Drug repurposing is a tangible strategy for developing antiviral agents within a short period. In general, drug repurposing starts with virtual screening of approved drugs employing docking simulations. However, the actual hit rate is low, and most of the predicted compounds are false positives. To tackle the challenges, we report advanced virtual screening with pre- and postdocking pharmacophore filtering of 6,218 drugs for COVID-19. Notably, 7 out of 38 compounds showed efficacies in inhibiting SARS-CoV-2 in Vero cells. Three of these were also found to inhibit SARS-CoV-2 in human Calu-3 cells. Furthermore, three drug combinations showed strong synergistic effects in SARS-CoV-2 inhibition at their clinically achievable concentrations.