Two novel oxetane containing lignans and a new megastigmane from Paronychia arabica and in silico analysis of them as prospective SARS-CoV-2 inhibitors.
Abdelsamed I ElshamyTarik A MohamedMahmoud A A IbrahimMontaser A M Al-HammadyTatsuro YoneyamaAkemi UmeyamaMohamed-Elamir F HegazyPublished in: RSC advances (2021)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- molecular docking
- anti inflammatory
- molecular dynamics simulations
- induced apoptosis
- high resolution
- amino acid
- genome wide
- oxidative stress
- signaling pathway
- pi k akt
- magnetic resonance
- gene expression
- wastewater treatment
- mass spectrometry
- protein protein
- cell proliferation
- cell death
- dna methylation
- transcription factor
- bioinformatics analysis
- small molecule
- coronavirus disease
- binding protein
- replacement therapy
- simultaneous determination