An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease.

Nemanja Djokovic, Dusan Ruzic, Teodora Djikic, Sandra Cvijic, Jelisaveta Ignjatovic, Svetlana Ibric, Katarina Baralic, Aleksandra Buha Djordjevic, Marijana Curcic, Danijela Djukic-Cosic, Katarina Nikolic,

10.1002/minf.202000187

Research curated

Abstract

Considering the urgent need for novel therapeutics in ongoing COVID-19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS-CoV-2 Main Protease (M^pro ). To screen FDA-approved drugs, we implemented structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data mining analysis of drug-gene-COVID-19 association. Through presented approach, we selected the most promising FDA approved drugs for further COVID-19 drug development campaigns and analysed them in context of available experimental data. To the best of our knowledge, this is unique in silico study which integrates structure-based molecular modeling of M^pro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.

Source: PubMed

Related molecules

Name	Synonyms	Genes
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Atazanavir
Ramipril	Ramiprilum
Lifitegrast
Salvianolic acid B
GHRP-2	Pralmorelin
Thymopentin
Naringin
Carfilzomib
Bimatoprost
Penfluridol
Ritonavir
Darunavir
Vilanterol
Dabigatran
Azilsartan
Telmisartan
Repaglinide
Nintendanib
Astilbin
Neohesperidin
Atorvastatin	Lipitor, Sortis
Bazedoxifene
Telaprevir
Bortezomib	Velcade, Chemobort, Bortecad
Eltrombopag
Montelukast
Pimozide
Lopinavir

Related interactions

Target	Drug	Type	Result
3C-like protease	Lopinavir	Computational	positive
3C-like protease	Atazanavir	Computational	positive
3C-like protease	Ramipril	Computational	positive
3C-like protease	Lifitegrast	Computational	positive
3C-like protease	Salvianolic acid B	Computational	positive
3C-like protease	GHRP-2	Computational	positive
3C-like protease	Thymopentin	Computational	positive
3C-like protease	Naringin	Computational	positive
3C-like protease	Carfilzomib	Computational	positive
3C-like protease	Bimatoprost	Computational	positive
3C-like protease	Penfluridol	Computational	positive
3C-like protease	Ritonavir	Computational	positive
3C-like protease	Darunavir	Computational	positive
3C-like protease	Vilanterol	Computational	positive
3C-like protease	Dabigatran	Computational	positive
3C-like protease	Azilsartan	Computational	positive
3C-like protease	Telmisartan	Computational	positive
3C-like protease	Pimozide	Computational	positive
3C-like protease	Repaglinide	Computational	positive
3C-like protease	Nintendanib	Computational	positive
3C-like protease	Eltrombopag	Computational	positive
3C-like protease	Astilbin	Computational	positive
3C-like protease	Neohesperidin	Computational	positive
3C-like protease	Atorvastatin	Computational	positive
3C-like protease	Bazedoxifene	Computational	positive
3C-like protease	Telaprevir	Computational	positive
3C-like protease	Bortezomib	Computational	positive
3C-like protease	Montelukast	Computational	positive