Theoretical and Computational Chemistry

Generate, Repurpose, Validate: A Receptor-Mediated Atom-by-Atom Drug Generation for SARS-Cov-2 Spike Protein and Similarity-Mapped Drug Repurposing for COVID-19 with Rigorous Free Energy Validation Using Well-Tempered Metadynamics

Arnab Mukherjee Indian institute of science education and research Pune


Finding a cure for Covid-19 is of immediate and paramount importance. In this study, we propose new and repurpose drugs to prevent SARS-Cov-2 (Covid-19) viral attack on human cells. Our study comprises three steps: generation of new molecules, structural similarity mapping to existing approved and investigational drugs, and validation of their binding strengths to the viral spike proteins based on rigorous all-atom well-tempered metadynamics free energy calculations. We show that some of our new molecules and some of the existing drugs bind more strongly than human ACE2 protein to the viral spike protein. Therefore, these drug molecules may have the potential to be repurposed as a preventive therapy for Covid-19, subject to further experimental verifications.


Thumbnail image of MSCovid19May20.pdf
download asset MSCovid19May20.pdf 25 MB [opens in a new tab]

Supplementary material

Thumbnail image of SICovid19May20.pdf
download asset SICovid19May20.pdf 5 MB [opens in a new tab]
Thumbnail image of DNVLive_covid_SI_small.mp4
download asset DNVLive_covid_SI_small.mp4 46 MB [opens in a new tab]
DNVLive covid SI small