Issue 67, 2020

Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19)

Abstract

The recent release of the main protein structures belonging to SARS CoV-2, responsible for the coronavirus disease-19 (COVID-19), strongly pushed for identifying valuable drug treatments. With this aim, we show a repurposing study on FDA-approved drugs applying a new computational protocol and introducing a novel parameter called IVSratio. Starting with a virtual screening against three SARS CoV-2 targets (main protease, papain-like protease, spike protein), the top-ranked molecules were reassessed combining the Inverse Virtual Screening novel approach and MM-GBSA calculations. Applying this protocol, a list of drugs was identified against the three investigated targets. Also, the top-ranked selected compounds on each target (rutin vs. main protease, velpatasvir vs. papain-like protease, lomitapide vs. spike protein) were further tested with molecular dynamics simulations to confirm the promising binding modes, obtaining encouraging results such as high stability of the complex during the simulation and a good protein–ligand interaction network involving some important residues of each target. Moreover, the recent outcomes highlighting the inhibitory activity of quercetin, a natural compound strictly related to rutin, on the SARS-CoV-2 main protease, strengthened the applicability of the proposed workflow.

Graphical abstract: Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19)

Supplementary files

Article information

Article type
Paper
Submitted
22 Okt 2020
Accepted
02 Nov 2020
First published
10 Nov 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 40867-40875

Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19)

S. De Vita, M. G. Chini, G. Lauro and G. Bifulco, RSC Adv., 2020, 10, 40867 DOI: 10.1039/D0RA09010G

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements