COVID-19 virus proteins are homologous to SARS-CoV with identity value ≥ 65%. As a world-renowned supplier of small molecular compounds, TargetMol performed a Swiss-Model Homology Modelling process to generate reliable protein models or 3D protein structures of RBD of Spike protein, ACE2, viral papain like protease (PLpro), main protease (3CLpro, also named 3-chymotrypsin-like protease), RNA-dependent RNA polymerase (RdRp), nsp16 (2′-O-methyltransferase, helicase), and X-domain. These 3D structures provide valuable information and foundation for structure-based virtual screening. Later, scientists from University of Chicago published a paper titled “Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2” at BioRxiv, where the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 was reported. Studies published in 2010 on SARS-CoV revealed inhibition of Nsp15 can slow viral replication. This suggests drugs designed to target Nsp15 could be developed as effective drugs against COVID-19.
Molecular docking-based virtual screening can speed up the development of COVID-19-targeted drugs with high-affinity by providing more drug candidates for screening and validation at molecular and cellular level. We used these 7 virus proteins and human ACE2 as targets to screen against TargetMol libraries (7729 compounds) and Bioactive compound library (7647 compounds) by using Surflex-Dock in the Sybyl-X 2.0 package.
To improve the virtual screening efficiency and reliability, we took a strategy of combining three rounds of screening: 2 rounds of molecular docking virtual screening plus 1 round of manual screening. Finally, 362 compounds were selected into this library: Anti-COVID-19 compound library (CADD). These compounds have been widely reported in the literature to have the potential of anti-cancer, anti-bacterial, anti-inflammation, or anti-oxidation activity; or have other potential targets. If they were confirmed and validated in antiviral activity assay, this screening strategy, equally a novel strategy of drug repurposing or target identification of natural products, could lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available.
|100 μL * 10 mM (in DMSO)||5977.00|