Natural phyto, compounds as possible noncovalent inhibitors against SARS-CoV2 protease: computational approach
| Autor: | Collins U. Ibeji, Joyce Oloaigbe Ogidigo, Emmanuel A. Iwuchukwu, Mahmoud E. S. Soliman, Okiemute Ajiroghene Okpalefe |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
030303 biophysics natural phytocompounds Molecular Dynamics Simulation Pharmacology 03 medical and health sciences chemistry.chemical_compound Pharmacokinetics Structural Biology medicine Humans Protease Inhibitors Molecular Biology chemistry.chemical_classification 0303 health sciences Protease biology Momordica SARS-CoV-2 Ribavirin Active site Hydroxychloroquine molecular dynamics simulations General Medicine Azadirachta biology.organism_classification COVID-19 Drug Treatment Molecular Docking Simulation MMGBA Enzyme chemistry biology.protein RNA Viral Peptide Hydrolases Research Article medicine.drug |
| Zdroj: | Journal of Biomolecular Structure and Dynamics Journal of Biomolecular Structure & Dynamics article-version (VoR) Version of Record |
| DOI: | 10.6084/m9.figshare.13141339.v1 |
| Popis: | At present, there is no cure or vaccine for the devastating new highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected people globally. Herein, we identified potent phytocompounds from two antiviral plants Momordica charantia L. and Azadirachta indica used locally for the treatment of viral and parasitic infections. Structure-based virtual screening and molecular dynamics (MD) simulation have been employed to study their inhibitory potential against the main protease (Mpro) SARS-CoV-2. A total of 86 compounds from M. charantia L. and A. indica were identified. The top six phytocompounds; momordicine, deacetylnimninene, margolonone, momordiciode F2, nimbandiol, 17-hydroxyazadiradione were examined and when compared with three FDA reference drugs (remdesivir, hydroxychloroquine and ribavirin). The top six ranked compounds and FDA drugs were then subjected to MD simulation and pharmacokinetic studies. These phytocompounds showed strong and stable interactions with the active site amino acid residues of SARS-CoV-2 Mpro similar to the reference compound. Results obtained from this study showed that momordicine and momordiciode F2 exhibited good inhibition potential (best MMGBA-binding energies; ���41.1 and ���43.4 kcal/mol) against the Mpro of SARS-CoV-2 when compared with FDA reference anti-viral drugs (Ribavirin, remdesivir and hydroxychloroquine). Per-residue analysis, root mean square deviation and solvent-accessible surface area revealed that compounds interacted with key amino acid residues at the active site of the enzyme and showed good system stability. The results obtained in this study show that these phytocompounds could emerge as promising therapeutic inhibitors for the Mpro of SARS-CoV-2. However, urgent trials should be conducted to validate this outcome. Communicated by Ramaswamy H. Sarma |
| Databáze: | OpenAIRE |
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