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Screening and identification of potential MERS-CoV papain-like protease (PLpro) inhibitors; Steady-state kinetic and Molecular dynamic studies.
Ali Dahhas, Mohammed; M Alkahtani, Hamad; Malik, Ajamaluddin; Almehizia, Abdulrahman A; Bakheit, Ahmed H; Akber Ansar, Siddique; AlAbdulkarim, Abdullah S; S Alrasheed, Lamees; Alsenaidy, Mohammad A.
  • Ali Dahhas M; Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • M Alkahtani H; Department of Pharmaceutical Chemistry, Department Chairman, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • Malik A; Department of Biochemistry, College of Science, King Saud University. King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
  • Almehizia AA; Department of Pharmaceutical Chemistry, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • Bakheit AH; Department of Pharmaceutical Chemistry, Department Chairman, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • Akber Ansar S; Department of Pharmaceutical Chemistry, Department Chairman, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • AlAbdulkarim AS; Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • S Alrasheed L; Department of Pharmaceutical Chemistry, Department Chairman, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • Alsenaidy MA; Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Saudi Pharm J ; 31(2): 228-244, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2238542
ABSTRACT
MERS-CoV belongs to the coronavirus group. Recent years have seen a rash of coronavirus epidemics. In June 2012, MERS-CoV was discovered in the Kingdom of Saudi Arabia, with 2,591 MERSA cases confirmed by lab tests by the end of August 2022 and 894 deaths at a case-fatality ratio (CFR) of 34.5% documented worldwide. Saudi Arabia reported the majority of these cases, with 2,184 cases and 813 deaths (CFR 37.2%), necessitating a thorough understanding of the molecular machinery of MERS-CoV. To develop antiviral medicines, illustrative investigation of the protein in coronavirus subunits are required to increase our understanding of the subject. In this study, recombinant expression and purification of MERS-CoV (PLpro), a primary goal for the development of 22 new inhibitors, were completed using a high throughput screening methodology that employed fragment-based libraries in conjunction with structure-based virtual screening. Compounds 2, 7, and 20, showed significant biological activity. Moreover, a docking analysis revealed that the three compounds had favorable binding mood and binding free energy. Molecular dynamic simulation demonstrated the stability of compound 2 (2-((Benzimidazol-2-yl) thio)-1-arylethan-1-ones) the strongest inhibitory activity against the PLpro enzyme. In addition, disubstitutions at the meta and para locations are the only substitutions that may boost the inhibitory action against PLpro. Compound 2 was chosen as a MERS-CoV PLpro inhibitor after passing absorption, distribution, metabolism, and excretion studies; however, further investigations are required.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Reviews Language: English Journal: Saudi Pharm J Year: 2023 Document Type: Article Affiliation country: J.jsps.2022.12.007

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Reviews Language: English Journal: Saudi Pharm J Year: 2023 Document Type: Article Affiliation country: J.jsps.2022.12.007