Rifampicin may be repurposed for COVID-19 treatment: Insights from an in-silico study

Abstract

Abstract The ongoing Coronavirus disease 2019 (COVID-19) outbreak has led to global epidemics with high morbidity and mortality. However, there are no efficacious therapeutic options available for the treatment of COVID-19. Considering this medical emergency, drug repurposing is the need of the hour. Therefore, this study aimed to determine possible COVID-19 drug candidates using virtual screening of selected FDA approved drugs by targeting the main protease (Mpro) of novel coronavirus (SARS-CoV-2). In this study, first, we have done an extensive literature search to find out the marketed FDA approved drug compounds available for human therapeutic applications having anti-viral and anti-bacterial properties. The preliminary reports paved the way for further studies that revealed some of the drugs approved to treat other viral or bacterial infections may be a promising drug candidate and can be repurposed for the treatment of COVID-19. Using a computer-aided drug designing approach, novel candidates for drug repurposing were identified. Based on our preliminary screening supported by previous works of literature, we selected Rifampicin, Ciclesonide, Reserpine, Loperamide, Elvitegravir, Brivudine, Pentoxifylline, Eugenol, Isoniazid, Tinidazole, Diethylcarbamazine, and Vancomycin to target the SARS-CoV-2 main protease (Mpro). These compounds were examined based on docking studies using Autodock 4.2 Autodock 4.2., visualization of the docked results using Pymol version 1.7.4.5 Edu and prediction of two main toxicity aspects hepatotoxicity and cytotoxicity to check the safety of the hit compounds. Selected drugs were ranked for potential efficacy against COVID-19 based on their binding energy. The docking results were found in the order of Rifampicin (-11.16), Ciclesonide (-8.77), Reserpine (-7.76), Loperamide (-7.63), Elvitegravir (-6.58), Brivudine (-6.06), Pentoxifylline (-5.64), Eugenol (-4.78), Isoniazid (-4.71), Tinidazole (-4.51), Diethylcarbamazine (-4.66), Vancomycin (-4.11). ). In the current study, Rifampicin appeared as the most promising drug showing a very good binding energy. Based on our preliminary insights from in silico studies, we propose that Rifampicin may be repurposed for the treatment of COVID-19 however it is pertinent to mention here that our findings need further validation by in vitro studies and clinical trials. In summary, the findings of this study suggest Rifampicin might be a promising drug for targeting the COVID-19 protease.