Telaprevir is a potential drug for repurposing against SARS-CoV-2: computational and in vitro studies

Amal Mahmoud; Ahmed Mostafa; Ahmed A Al-Karmalawy; Ahmad Zidan; Hamada S Abulkhair; Sara H Mahmoud; Mahmoud Shehata; Mahmoud M Elhefnawi; Mohamed A Ali

doi:10.1016/j.heliyon.2021.e07962

Telaprevir is a potential drug for repurposing against SARS-CoV-2: computational and in vitro studies

Heliyon. 2021 Sep;7(9):e07962. doi: 10.1016/j.heliyon.2021.e07962. Epub 2021 Sep 9.

Authors

Affiliations

¹ Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box. 1982, 31441, Dammam, Saudi Arabia.
² Center of Scientific Excellence for Infuenza Viruses, National Research Centre, 12622 Dokki, Giza, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt.
⁴ Department of Bioinformatics, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.
⁵ Clinical Research Team, Monof Chest Hospital, Ministry of Health, Egypt.
⁶ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Nasr City 11884, Cairo, Egypt.
⁷ Biomedical Informatics and Cheminformatics Group, Informatics and Systems Department, National Research Centre, Cairo, Egypt.

Abstract

Drug repurposing is an important approach to the assignment of already approved drugs for new indications. This technique bypasses some steps in the traditional drug approval system, which saves time and lives in the case of pandemics. Direct acting antivirals (DAAs) have repeatedly repurposed from treating one virus to another. In this study, 16 FDA-approved hepatitis C virus (HCV) DAA drugs were studied to explore their activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human and viral targets. Among the 16 HCV DAA drugs, telaprevir has shown the best in silico evidence to work on both indirect human targets (cathepsin L [CTSL] and human angiotensin-converting enzyme 2 [hACE2] receptor) and direct viral targets (main protease [M^pro]). Moreover, the docked poses of telaprevir inside both hACE2 and M^pro were subjected to additional molecular dynamics simulations monitored by calculating the binding free energy using MM-GBSA. In vitro analysis of telaprevir showed inhibition of SARS-CoV-2 replication in cell culture (IC₅₀ = 11.552 μM, CC₅₀ = 60.865 μM, and selectivity index = 5.27). Accordingly, based on the in silico studies and supported by the presented in vitro analysis, we suggest that telaprevir may be considered for therapeutic development against SARS-CoV-2.

Keywords: Anti-HCV; Drug repurposing; Protease inhibitor; SARS-CoV-2; Telaprevir.