The battle against SARS-CoV-2 coronavirus is the focal point for the global pandemic that has affected millions of lives worldwide. The need for effective and selective therapeutics for the treatment of the disease caused by SARS-CoV-2 is critical.
Herein, we performed computational de novo design incorporating molecular docking
studies, molecular dynamics simulations, absolute binding energy calculations, and
steered molecular dynamics simulations for the discovery of potential compounds with
high affinity towards SARS-CoV-2 spike RBD. By leveraging ZINC15 database, a total
of 1282 in-clinical and FDA approved drugs were filtered out from nearly 0.5 million
protomers of relatively large compounds (MW > 500, and LogP ≤ 5). Our results depict plausible mechanistic aspects related to the blockage of SARS-CoV-2 spike RBD
by the top hits discovered. We found that the most promising candidates, namely,
ZINC95628821, ZINC95617623, and ZINC261494658, strongly bind to the spike RBD and interfere with the human ACE2 receptor. These findings accelerate the rational
design of selective inhibitors targeting the spike RBD protein of SARS-CoV-2.
Repurposing of FDA-Approved Drugs for the Discovery of Inhibitors of Dengue Virus NS2B-NS3 Protease by Docking, Consensus Scoring, and Molecular Dynamics Simulations