Şevki Adem1, Volkan Eyupoglu1, Iqra Sarfraz2, Azhar Rasul3, Ameer Fawad Zahoor4, Muhammad Ali5, Mohnad Abdalla6, Ibrahim M Ibrahim7, Abdo A Elfiky7. 1. Department of Chemistry, Faculty of Sciences, Çankırı Karatekin University, 18100 Çankırı, Turkey. 2. Cell and Molecular Biology Lab, Department of Zoology, Faculty of Life Sciences, Government College University Faisalabad, 38000 Faisalabad, Pakistan. 3. Cell and Molecular Biology Lab, Department of Zoology, Faculty of Life Sciences, Government College University Faisalabad, 38000 Faisalabad, Pakistan. Electronic address: drazharrasul@gmail.com. 4. Department of Chemistry, Faculty of Life Sciences, Government College University Faisalabad, 38000 Faisalabad, Pakistan. 5. Vice Chancellor, Quaid-e-Azam University (QAU), Islamabad. 6. Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province 250012, PR China. 7. Biophysics Department, Faculty of Sciences, Cairo University, Giza, 12613, Egypt.
Abstract
BACKGROUND: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. PURPOSE: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. METHODS: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. RESULTS: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. CONCLUSION: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.
BACKGROUND:SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. PURPOSE: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. METHODS: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. RESULTS: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. CONCLUSION: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.
Authors: M Amoretti; C Amsler; G Bonomi; A Bouchta; P Bowe; C Carraro; C L Cesar; M Charlton; M J T Collier; M Doser; V Filippini; K S Fine; A Fontana; M C Fujiwara; R Funakoshi; P Genova; J S Hangst; R S Hayano; M H Holzscheiter; L V Jørgensen; V Lagomarsino; R Landua; D Lindelöf; E Lodi Rizzini; M Macrì; N Madsen; G Manuzio; M Marchesotti; P Montagna; H Pruys; C Regenfus; P Riedler; J Rochet; A Rotondi; G Rouleau; G Testera; A Variola; T L Watson; D P van der Werf Journal: Nature Date: 2002-09-18 Impact factor: 49.962
Authors: Eric F Pettersen; Thomas D Goddard; Conrad C Huang; Gregory S Couch; Daniel M Greenblatt; Elaine C Meng; Thomas E Ferrin Journal: J Comput Chem Date: 2004-10 Impact factor: 3.376
Authors: James C Phillips; Rosemary Braun; Wei Wang; James Gumbart; Emad Tajkhorshid; Elizabeth Villa; Christophe Chipot; Robert D Skeel; Laxmikant Kalé; Klaus Schulten Journal: J Comput Chem Date: 2005-12 Impact factor: 3.376
Authors: Nikheel Bhojraj Rathod; Nariman Elabed; Fatih Özogul; Joe M Regenstein; Charis M Galanakis; Sulaiman Omar Aljaloud; Salam A Ibrahim Journal: Front Microbiol Date: 2022-06-22 Impact factor: 6.064
Authors: Ranjan K Mohapatra; Kuldeep Dhama; Amr Ahmed El-Arabey; Ashish K Sarangi; Ruchi Tiwari; Talha Bin Emran; Mohammad Azam; Saud I Al-Resayes; Mukesh K Raval; Veronique Seidel; Mohnad Abdalla Journal: J King Saud Univ Sci Date: 2021-10-07
Authors: Montaña Cámara; María Cortes Sánchez-Mata; Virginia Fernández-Ruiz; Rosa María Cámara; Elena Cebadera; Laura Domínguez Journal: Foods Date: 2021-05-14
Authors: Giuseppe Carota; Simone Ronsisvalle; Federica Panarello; Daniele Tibullo; Anna Nicolosi; Giovanni Li Volti Journal: J Clin Med Date: 2021-05-25 Impact factor: 4.241