Two novel oxetane containing lignans and a new megastigmane from Paronychia arabica and in silico analysis of them as prospective SARS-CoV-2 inhibitors. Issue 33 (4th June 2021)

• Record Type: Journal Article
• Authors: Elshamy, Abdelsamed I.; Mohamed, Tarik A.; Ibrahim, Mahmoud A. A.; Atia, Mohamed A. M.; Yoneyama, Tatsuro; Umeyama, Akemi; Hegazy, Mohamed-Elamir F.
• Is Part Of: RSC advances. Volume 11:Issue 33(2021)
• Page Start: 20151
• Page End: 20163
• Publication Date: 2021-06-04
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1ra02486h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : The hydromethanolic extract of Paronychia arabica aerial parts afforded two oxetane containing lignans, paronychiarabicine A (1 ) and B (2 ), and one new megastigmane, paronychiarabicastigmane A (3 ), alongside a known secondary metabolites (4–14 ). Abstract : The chemical characterization of the extract of the aerial parts of Paronychia arabica afforded two oxetane containing lignans, paronychiarabicine A (1 ) and B (2 ), and one new megastigmane, paronychiarabicastigmane A (3 ), alongside a known lignan (4 ), eight known phenolic compounds (5–12 ), one known elemene sesquiterpene (13 ) and one steroid glycoside (14 ). The chemical structures of the isolated compounds were constructed based upon the HRMS, 1D, and 2D-NMR results. The absolute configurations were established via NOESY experiments as well as experimental and TDDFT-calculated electronic circular dichroism (ECD). Utilizing molecular docking, the binding scores and modes of compounds 1–3 towards the SARS-CoV-2 main protease (M pro ), papain-like protease (PL pro ), and RNA-dependent RNA polymerase (RdRp) were revealed. Compound 3 exhibited a promising docking score (−9.8 kcal mol −1 ) against SARS-CoV-2 M pro by forming seven hydrogen bonds inside the active site with the key amino acids. The reactome pathway enrichment analysis revealed a correlation between the inhibition of GSK3 and GSK3B genes (identified as the main targets of megastigmane treatment) and significant inhibition of SARS-CoV-1 viral replication in infected Vero E6 cells. Our results manifest a novel understanding of genes, proteins and corresponding pathways against SARS-CoV-2 infection and could facilitate the identification and characterization of novel therapeutic targets as treatments of SARS-CoV-2 infection.