RHAMNETIN IS A BETTER INHIBITOR OF SARS-COV-2 2'-O-METHYLTRANSFERASE THAN DOLUTEGRAVIR: A COMPUTATIONAL PREDICTION

Adekunle B Rowaiye; Angus Nnamdi Oli; Olukemi A Onuh; Nkoli W Emeter; Doofan Bur; Oluwaseun A Obideyi; Oluyomi Cornelius Dayisi; Jude N Akpa; Lovelyn Birah; Edward E Omaka; Frances Otibhor Iseghohi; Akinbobola Peace Otitoju; Philip F Uzor; Jude Nnaemeka Okoyeh

doi:10.21010/Ajid.v16i2.9

RHAMNETIN IS A BETTER INHIBITOR OF SARS-COV-2 2'-O-METHYLTRANSFERASE THAN DOLUTEGRAVIR: A COMPUTATIONAL PREDICTION

Afr J Infect Dis. 2022 May 6;16(2):80-96. doi: 10.21010/Ajid.v16i2.9. eCollection 2022.

Authors

Affiliations

¹ Department of Medical Biotechnology, National Biotechnology Development Agency, Lugbe, Abuja, Nigeria.
² Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University Awka, Nigeria.
³ Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria.
⁴ Department of Biology and Clinical Laboratory Science, Division of Arts and Sciences, Neumann University, One Neumann Drive, Aston, PA 19014-1298, USA.

Abstract

Background: The 2'-O-methyltransferase is responsible for the capping of SARS-CoV-2 mRNA and consequently the evasion of the host's immune system. This study aims at identifying prospective natural inhibitors of the active site of SARS-CoV-2 2'O-methyltransferase (2'-OMT) through an in silico approach.

Materials and methods: The target was docked against a library of natural compounds obtained from edible African plants using PyRx - virtual screening software. The antiviral agent, Dolutegravir which has a binding affinity score of -8.5 kcal mol^-1 with the SARS-CoV-2 2'-OMT was used as a standard. Compounds were screened for bioavailability through the SWISSADME web server using their molecular descriptors. Screenings for pharmacokinetic properties and bioactivity were performed with PKCSM and Molinspiration web servers respectively. The PLIP and Fpocket webservers were used for the binding site analyses. The Galaxy webserver was used for simulating the time-resolved motions of the apo and holo forms of the target while the MDWeb web server was used for the analyses of the trajectory data.

Results: The Root-Mean-Square-Deviation (RMSD) induced by Rhamnetin is 1.656A⁰ compared to Dolutegravir (1.579A⁰). The average B-factor induced by Rhamnetin is 113.75 while for Dolutegravir is 78.87; the Root-Mean-Square-Fluctuation (RMSF) for Rhamnetin is 0.75 and for Dolutegravir is 0.67. Also, at the active site, Rhamnetin also has a binding affinity score of -9.5 kcal mol^-1 and forms 7 hydrogen bonds compared to Dolutegravir which has -8.5 kcal mol^-1 and forms 4 hydrogen bonds respectively.

Conclusion: Rhamnetin showed better inhibitory activity at the target's active site than Dolutegravir.

Keywords: 2’-O-methyltransferase Inhibition; COVID-19; Computational Drug prediction; Coronavirus disease; SARS-CoV-2.