Repurposing FDA-approved drugs cetilistat, abiraterone, diiodohydroxyquinoline, bexarotene, and remdesivir as potential inhibitors against RNA dependent RNA polymerase of SARS-CoV-2: A comparative in silico perspective

• Published in: Informatics in medicine unlocked Vol. 36; p. 101147
• Main Authors: Shahabadi, Nahid, Zendehcheshm, Saba, Mahdavi, Mohammad, Khademi, Fatemeh
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2023; The Authors. Published by Elsevier Ltd; Elsevier
• Subjects: Coronavirus; Docking; Drug repurposing; Dynamic; RNA-Dependent RNA polymerase; Virtual screening; Drug repurposing; Virtual screening; Docking; Dynamic; Coronavirus; RNA-Dependent RNA polymerase
• ISSN: 2352-9148; 2352-9148
• DOI: 10.1016/j.imu.2022.101147

Vaccines are undoubtedly the most effective means of combating viral diseases like COVID-19. However, there are risks associated with vaccination, such as incomplete viral deactivation or potential adverse effects in humans. However, designing and developing a panel of new drug molecules is always encouraged. In an emergency, drug repurposing research is one of the most potent and rapid options. RdRp (RNA-dependent RNA polymerase) has been discovered to play a pivotal role in viral replication. In this study, FDA-approved drugs bexarotene, diiodohydroxyquinoline, abiraterone, cetilistat, and remdesivir were repurposed against the RdRp by molecular modeling, docking, and dynamic simulation. Furthermore, to validate the potency of these drugs, we compared them to the antiviral remdesivir, which inhibits RdRp. Our finding indicated that the selected drugs have a high potential to be developed as RdRp inhibitors and, with further validation studies, could serve as potential drugs for the treatment of COVID-19. [Display omitted] •The inhibitory activity of some drugs against RNA dependent RNA polymerase was studied by molecular docking and MD simulation.•Bexarotene and abiraterone binds more tightly to RNA dependent RNA polymerase compared to remdesivir.•The binding energies of cetilistat are equal to that of remdesivir.•The MD simulation results showed that the interaction of bexarotene causes the stability of the protein.•The drugs could be the potential drug of choice for the treatment of COVID-19 with further ex vivo and in vivo examinations.