Open AccessDrugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay
Author(s) -
Woo Dae Jang,
Sangeun Jeon,
Seungtaek Kim,
Sang Yup Lee
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2024302118
Subject(s) - virtual screening , drug repositioning , repurposing , covid-19 , pharmacophore , vero cell , drug , pharmacology , false positive paradox , drug discovery , virology , computational biology , chemistry , medicine , biology , bioinformatics , computer science , virus , infectious disease (medical specialty) , ecology , disease , pathology , machine learning , outbreak
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.