Autochthonous Peruvian natural plants as potential SARS-CoV-2 Mpro main protease inhibitors

Peralta-Moreno, M. N. ; Antón-Muñoz, V. ; Ortega-Alarcón, D. ; Jiménez-Alesanco, A. (Universidad de Zaragoza) ; Vega, S. ; Abian, O. (Universidad de Zaragoza) ; Velázquez-Campoy, A. (Universidad de Zaragoza) ; Thomson, T. M. ; Granadino-Roldán, J. M. ; Machicado, C. ; Rubio-Martínez, J.

Resumen: Over 750 million cases of COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), have been reported since the onset of the global outbreak. The need for effective treatments has spurred intensive research for therapeutic agents based on pharmaceutical repositioning or natural products. In light of prior studies asserting the bioactivity of natural compounds of the autochthonous Peruvian flora, the present study focuses on the identification SARS-CoV-2 Mpro main protease dimer inhibitors. To this end, a target-based virtual screening was performed over a representative set of Peruvian flora-derived natural compounds. The best poses obtained from the ensemble molecular docking process were selected. These structures were subjected to extensive molecular dynamics steps for the computation of binding free energies along the trajectory and evaluation of the stability of the complexes. The compounds exhibiting the best free energy behaviors were selected for in vitro testing, confirming the inhibitory activity of Hyperoside against Mpro, with a Ki value lower than 20 µM, presumably through allosteric modulation.

Idioma: Inglés

DOI: 10.3390/ph16040585

Año: 2023

Publicado en: Pharmaceuticals 16, 4 (2023), 585 [20 pp.]
ISSN: 1424-8247

Factor impacto JCR: 4.3 (2023)

Categ. JCR: PHARMACOLOGY & PHARMACY rank: 69 / 354 = 0.195 (2023) - Q1 - T1
Categ. JCR: CHEMISTRY, MEDICINAL rank: 20 / 72 = 0.278 (2023) - Q2 - T1

Factor impacto CITESCORE: 6.1 - Pharmaceutical Science (Q2) - Drug Discovery (Q2) - Molecular Medicine (Q2)

Factor impacto SCIMAGO: 0.845 - Pharmaceutical Science (Q1) - Drug Discovery (Q2) - Molecular Medicine (Q2)

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2019-107139RB-C21
Financiación: info:eu-repo/grantAgreement/ES/DGA/B25-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA/E45-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI21-00394
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739
Financiación: info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/CEX2021-001202-M
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)