A study by the Roviri and Virgili University of Tarragona shows that an anti-inflammatory for human use and one for veterinary use inhibit a key enzyme in the replication and transcription of the virus responsible for covid-19. The results of the work have been validated by the Covid Moonshot initiative, which has carried out in vitro studies and evaluated its bioactivity, and have been published in the «International Journal of Molecular Sciences».
Finding drugs that can inhibit infection caused by SARS-CoV-2 is an essential step while waiting for the vaccine that can definitively stop the virus from spreading. In this sense, the research group in Chemoinformatics and Nutrition at the URV has carried out a computational screening to predict whether there is any medicine authorized to treat any other pathology that can inhibit the main virus protease (M-pro), a key aspect already that this enzyme has an essential role in the replication of the virus.
The objective of the study has been to use computational techniques to predict whether 6,466 drugs authorized by various drug agencies for both human and veterinary use could be used to inhibit the M-pro enzyme.
The work shows that one anti-inflammatory for human use and one for veterinary use – celecoxib and carprofen- inhibit a key enzyme in the replication and transcription of the virus responsible for Covid-19.
The aim of the study has been to use computational techniques to predict whether 6,466 drugs licensed by various drug agencies for both human and veterinary use could be used to inhibit the M-pro enzyme.
This enzyme is the protease responsible for cutting two polypeptides, a type of molecule produced by the virus itself, and generating a whole series of proteins that are essential for its reproduction. Some of the trials coordinated by the World Health Organization (WHO) against the COVID-19 pandemic also aim to inhibit M-pro using two antiretrovirals such as lopinavir and ritonavir, which are drugs designed initially to treat HIV.
The data indicates that seven of these 6,466 drugs can inhibit M-pro, therefore, virus replication. The results with these seven molecules have been shared with the international initiative Covid Moonshot that has selected two of these seven (carprofen and celecoxib) to verify in vitro their ability to inhibit the main protease of the virus, M-pro.
The work is the first published worldwide on drug repositioning as SARS-CoV-2 M-pro inhibitors in which computational predictions are experimentally corroborated.
The results obtained show how a concentration of 50 µM (micromol-liter) of celecoxib or carprofen, both molecules are capable of inhibiting the in vitro activity of M-pro (with an inhibition of 11.9% by celecoxib and 4.0% by carprofen). Although not very powerful inhibitors, the study indicates that both compounds can be used as a starting point to design even more powerful derivatives.
The work is the first published worldwide on drug repositioning as SARS-CoV-2 M-pro inhibitors in which computational predictions are experimentally corroborated. The remaining 5 molecules are expected to be selected shortly by the Covid Moonshot initiative to also check their bioactivity. .