PT  - JOURNAL ARTICLE
AU  - Shalini Saxena
AU  - Kranti Meher
AU  - Madhuri Rotella
AU  - Subhramanyam Vangala
AU  - Satish Chandran
AU  - Nikhil Malhotra
AU  - Ratnakar Palakodeti
AU  - Sreedhara R Voleti
AU  - Uday Saxena
TI  - Identification of SGLT2 inhibitor Ertugliflozin as a treatment for COVID-19 using computational and experimental paradigm
AID  - 10.1101/2021.06.18.448921
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.18.448921
4099  - http://biorxiv.org/content/early/2021/06/18/2021.06.18.448921.short
4100  - http://biorxiv.org/content/early/2021/06/18/2021.06.18.448921.full
AB  - Drug repurposing can expedite the process of drug development by identifying known drugs which are effective against SARS-CoV-2. The RBD domain of SARS-CoV-2 Spike protein is a promising drug target due to its pivotal role in viral-host attachment. These specific structural domains can be targeted with small molecules or drug to disrupt the viral attachment to the host proteins. In this study, FDA approved Drugbank database were screened using a virtual screening approach and computational chemistry methods. Five drugs were short listed for further profiling based on docking score and binding energies. Further these selected drugs were tested for their in vitro biological activity. There was significant correlation between the prediction from computational studies and the actual RBD-ACE2 binding inhibition by the drugs. Then, we performed a series of studies that mimic some of the biological events seen in COVID-19 patients such as secretion of IL1β, presentation of a more thrombogenic endothelium by production of thrombomodulin and accumulation of inflammatory cells such as monocytes in the lungs. Of all the drugs, most promising drug was Ertugliflozin which is used for type-2 diabetes. This drug possesses several desired properties and may be a good candidate for immediate repurposing for treatment of COVID-19.Competing Interest StatementThe authors have declared no competing interest.