Carotane sesquiterpenes from Ferula vesceritensis: in silico analysis as SARS-CoV-2 binding inhibitors

Tarik A Mohamed; Abdelsamed I Elshamy; Mahmoud A A Ibrahim; Ammar Zellagui; Mahmoud F Moustafa; Alaa H M Abdelrahman; Shinji Ohta; Paul W Pare; Mohamed-Elamir F Hegazy

doi:10.1039/d0ra06901a

Carotane sesquiterpenes from Ferula vesceritensis: in silico analysis as SARS-CoV-2 binding inhibitors

RSC Adv. 2020 Sep 18;10(57):34541-34548. doi: 10.1039/d0ra06901a. eCollection 2020 Sep 16.

Authors

Tarik A Mohamed¹, Abdelsamed I Elshamy², Mahmoud A A Ibrahim³, Ammar Zellagui⁴, Mahmoud F Moustafa^{5

6}, Alaa H M Abdelrahman³, Shinji Ohta⁷, Paul W Pare⁸, Mohamed-Elamir F Hegazy¹

Affiliations

¹ Chemistry of Medicinal Plants Department, National Research Centre 33 El-Bohouth St., Dokki Giza 12622 Egypt me.fathy@nrc.sci.eg +20-23337093.
² Chemistry of Natural Compounds Department, National Research Centre 33 El Bohouth St., Dokki Giza 12622 Egypt.
³ Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University Minia 61519 Egypt.
⁴ Laboratory of Biomolecule and Plant Breeding, Life Science and Nature Department, Faculty of Exact Science and Life Science and Nature, University of Larbi Ben Mhidi 4000 Oum El Bouaghi Algeria.
⁵ Department of Biology, College of Science, King Khalid University 9004 Abha Kingdom of Saudi Arabia.
⁶ Department of Botany & Microbiology, Faculty of Science, South Valley University Qena Egypt.
⁷ Graduate School of Integrated Sciences for Life, Hiroshima University 1-7-1 Kagamiyama Higashi-Hiroshima 739-8521 Japan.
⁸ Department of Chemistry and Biochemistry, Texas Tech University Lubbock TX 79409 USA paul.pare@ttu.edu +1 806 742 1289.

Abstract

Two sesquiterpenes, 8α-anisate-dauc-4-ene-3,9-dione (webiol anisate) (1) and 10α-acetoxy-6α-benzoate-jaeschkeanadiol (2) as well as, ten known analogues (3-10), and two sesquiterpene coumarins (11-12) were isolated from an organic root extract of Ferula vesceritensis (Fam. Apiaceae). Chemical structures were elucidated based on IR, 1D- and 2D-NMR and HRMS, spectroscopic analyses. With molecular overlap observed between two protease inhibitors that are being examined as anti-COVID-19 drugs, and sesquiterpenes isolated here, metabolite molecular docking calculations were made using the main protease (M^pro), which is required for viral multiplication as well as RNA-dependent RNA polymerase (RdRp). In silico binding-inhibition analysis predicted that select F. vesceritensis sesquiterpenes can bind to these enzymes required for viral replication. Structures of the isolated constituents were also consistent with the chemo-systematic grouping of F. vesceritensis secondary metabolites with other Ferula species.