In silico screening of FDA approved drugs reveals ergotamine and dihydroergotamine as potential coronavirus main protease enzyme inhibitors

Arun Bahadur Gurung; Mohammad Ajmal Ali; Joongku Lee; Mohammad Abul Farah; Khalid Mashay Al-Anazi

doi:10.1016/j.sjbs.2020.06.005

In silico screening of FDA approved drugs reveals ergotamine and dihydroergotamine as potential coronavirus main protease enzyme inhibitors

Saudi J Biol Sci. 2020 Oct;27(10):2674-2682. doi: 10.1016/j.sjbs.2020.06.005. Epub 2020 Jun 10.

Authors

Arun Bahadur Gurung¹, Mohammad Ajmal Ali², Joongku Lee³, Mohammad Abul Farah⁴, Khalid Mashay Al-Anazi⁴

Affiliations

¹ Department of Basic Sciences and Social Sciences, North-Eastern Hill University, Shillong 793022, Meghalaya, India.
² Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
³ Department of Environment and Forest Resources, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
⁴ Genetics Laboratory, Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

Coronaviruses with the largest viral genomes are positive-sense RNA viruses associated with a history of global epidemics such as the severe respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS) and recently the coronavirus disease 2019 (COVID-19). There has been no vaccines or drugs available for the treatment of human coronavirus infections to date. In the present study, we have explored the possibilities of FDA approved drugs as potential inhibitors of the coronavirus main protease, a therapeutically important drug target playing a salient role in the maturation and processing of the viral polyproteins and are vital for viral replication and transcription. We have used molecular docking approach and have successfully identified the best lead molecules for each enzyme target. Interestingly, the anti-migraine drugs such as ergotamine and its derivative, dihydroergotamine were found to bind to all the three target enzymes within the Cys-His catalytic dyad cleft with lower binding energies as compared to the control inhibitors (α-ketoamide 13b, SG85 and GC813) and the molecules are held within the pocket through a good number of hydrogen bonds and hydrophobic interactions. Hence both these lead molecules can be further taken for wet-lab experimentation studies before repurposing them as anti-coronaviral drug candidates.

Keywords: 2019-nCoV; COVID-19; Coronaviral main protease; Coronaviruses; Dihydroergotamine; Ergotamine; FDA approved drugs; MERS-CoV; SARS-CoV; SARS-CoV-2.