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Rutin and flavone analogs as prospective SARS-CoV-2 main protease inhibitors: In silico drug discovery study.
Ibrahim, Mahmoud A A; Mohamed, Eslam A R; Abdelrahman, Alaa H M; Allemailem, Khaled S; Moustafa, Mahmoud F; Shawky, Ahmed M; Mahzari, Ali; Hakami, Abdulrahim Refdan; Abdeljawaad, Khlood A A; Atia, Mohamed A M.
  • Ibrahim MAA; Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt. Electronic address: m.ibrahim@compchem.net.
  • Mohamed EAR; Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt.
  • Abdelrahman AHM; Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt.
  • Allemailem KS; Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
  • Moustafa MF; Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; Department of Botany & Microbiology, Faculty of Science, South Valley University, Qena, Egypt.
  • Shawky AM; Science and Technology Unit (STU), Umm Al-Qura University, Makkah, 21955, Saudi Arabia.
  • Mahzari A; Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha, Saudi Arabia.
  • Hakami AR; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, 61481, Saudi Arabia.
  • Abdeljawaad KAA; Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt.
  • Atia MAM; Molecular Genetics and Genome Mapping Laboratory, Genome Mapping Department, Agricultural Genetic Engineering Research Institute (AGERI), Agricultural Research Center (ARC), Giza, 12619, Egypt. Electronic address: matia@ageri.sci.eg.
J Mol Graph Model ; 105: 107904, 2021 06.
Article in English | MEDLINE | ID: covidwho-1142056
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a new pandemic characterized by quick spreading and illness of the respiratory system. To date, there is no specific therapy for Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Flavonoids, especially rutin, have attracted considerable interest as a prospective SARS-CoV-2 main protease (Mpro) inhibitor. In this study, a database containing 2017 flavone analogs was prepared and screened against SARS-CoV-2 Mpro using the molecular docking technique. According to the results, 371 flavone analogs exhibited good potency towards Mpro with docking scores less than -9.0 kcal/mol. Molecular dynamics (MD) simulations, followed by molecular mechanics-generalized Born surface area (MM/GBSA) binding energy calculations, were performed for the top potent analogs in complex with Mpro. Compared to rutin, PubChem-129-716-607 and PubChem-885-071-27 showed better binding affinities against SARS-CoV-2 Mpro over 150 ns MD course with ΔGbinding values of -69.0 and -68.1 kcal/mol, respectively. Structural and energetic analyses demonstrated high stability of the identified analogs inside the SARS-CoV-2 Mpro active site over 150 ns MD simulations. The oral bioavailabilities of probable SARS-CoV-2 Mpro inhibitors were underpinned using drug-likeness parameters. A comparison of the binding affinities demonstrated that the MM/GBSA binding energies of the identified flavone analogs were approximately three and two times less than those of lopinavir and baicalein, respectively. In conclusion, PubChem-129-716-607 and PubChem-885-071-27 are promising anti-COVID-19 drug candidates that warrant further clinical investigations.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Flavones / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Humans Language: English Journal: J Mol Graph Model Journal subject: Molecular Biology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Flavones / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Humans Language: English Journal: J Mol Graph Model Journal subject: Molecular Biology Year: 2021 Document Type: Article