According to computer simulations, dipyridamole targets the main replication protein of SARS-CoV-2, called Mpro.

Key Messages

An “in-silico” experiment is one performed via a computer simulation. These types of virtual experiments enable us to test theories about drugs and their biological targets before testing them in the lab or in animals or humans.

A critical protein required for SARS-CoV-2 replication is known as Mpro, and it is therefore an attractive drug target for treating COVID-19.

In this in-silico drug repurposing study, computer simulations identified dipyridamole from a database of existing drugs as a strong potential inhibitor of the SARS-CoV-2 Mpro protein.

This means dipyridamole may act as a SARS-CoV-2 replication inhibitor and could offer a new drug treatment option for COVID-19.

Molecular Informatics

Publication Date: May 1, 2021
Peer Reviewed: Yes
Publication Type: Original | Preclinical

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


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 (Mpro ). 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 Mpro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.