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Potential inhibitory properties of structurally modified quercetin/isohamnetin glucosides against SARS-CoV-2 Mpro; molecular docking and dynamics simulation strategies.
Adegbola, Peter Ifeoluwa; Fadahunsi, Olumide Samuel; Ogunjinmi, Oluwasayo Esther; Adegbola, Aanuoluwa Eunice; Ojeniyi, Fiyinfoluwa Demilade; Adesanya, Adetayo; Olagoke, Emmanuel; Adisa, Ayobami Damilare; Ehigie, Adeola Folasade; Adetutu, Adewale; Semire, Banjo.
  • Adegbola PI; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Fadahunsi OS; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Ogunjinmi OE; Department of Industrial Chemistry, Faculty of Natural and Applied Sciences, First Technical University, Ibadan, Nigeria.
  • Adegbola AE; Department of Pure and Applied Chemistry, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Ojeniyi FD; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Adesanya A; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Olagoke E; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Adisa AD; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Ehigie AF; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Adetutu A; Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
  • Semire B; Department of Pure and Applied Chemistry, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
Inform Med Unlocked ; 37: 101167, 2023.
Article in English | MEDLINE | ID: covidwho-2179697
ABSTRACT
Concerned organizations and individuals are fully engaged in seeking appropriate measures towards managing Severe Acute Respiratory Syndrome Coronavirus 2 (SAR-CoV-2) infection because of the unprecedented economic and health impact. SAR-CoV-2 Main protease (SARS-CoV-2 Mpro) is unique to the survival and viability of the virus. Therefore, inhibition of Mpro can block the viral propagation. Thirty (30) derivatives were built by changing the glucosides in the Meta and para position of quercetin and isohamnetin. Molecular docking analysis was used for the screening of the compounds. Dynamics simulation was performed to assess the stability of the best pose docked complex. Molecular mechanics binding free energy calculation was done by Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA). Overall analysis showed that the compounds are allosteric inhibitors of SARS-CoV-2 Mpro. Dynamic simulation analysis established the stability of Mpro-ISM-1, Mpro-ISD-3, Mpro-IST-2, Mpro-QM-2, and Mpro-QD-6 complexes with a maximum of 7 hydrogen bonds involved in their interaction. The MMPBSA binding free energies for ISM-1, ISD-3, IST-2, QM-2, and QD-6 were -92.47 ± 9.06, -222.27 ± 32.5, 180.72 ± 47.92, 156.46 ± 49.88 and -93.52 ± 48.75 kcal/mol respectively. All the compounds showed good pharmacokinetic properties, while only ISM-1 inhibits hERG and might be cardio-toxic. Observations in this study established that the glucoside position indeed influenced the affinity for SARS-CoV-2 Mpro. The study also suggested the potentials of ISD-3, QM-2 and QD-6 as potent inhibitors of the main protease, further experimental and clinical studies are however necessary to validate and establish the need for further drug development processes. Therefore, future studies will be on the chemical synthesis of the compounds and investigation of the in-vitro inhibition of SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study / Reviews Language: English Journal: Inform Med Unlocked Year: 2023 Document Type: Article Affiliation country: J.imu.2023.101167

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Prognostic study / Reviews Language: English Journal: Inform Med Unlocked Year: 2023 Document Type: Article Affiliation country: J.imu.2023.101167