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Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors.
Alhadrami, Hani A; Burgio, Gaia; Thissera, Bathini; Orfali, Raha; Jiffri, Suzan E; Yaseen, Mohammed; Sayed, Ahmed M; Rateb, Mostafa E.
  • Alhadrami HA; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia.
  • Burgio G; Molecular Diagnostic Laboratory, King Abdulaziz University Hospital, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia.
  • Thissera B; Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia.
  • Orfali R; School of Computing, Engineering and Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.
  • Jiffri SE; School of Computing, Engineering and Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.
  • Yaseen M; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia.
  • Sayed AM; King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia.
  • Rateb ME; School of Computing, Engineering and Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK.
Mar Drugs ; 20(3)2022 Feb 24.
Article in English | MEDLINE | ID: covidwho-1725847
ABSTRACT
The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 Mpro with IC50 value of 0.47 µM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 Mpro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related Mpro inhibitors.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Piperazines / Cysteine Proteinase Inhibitors / Indole Alkaloids / Coronavirus 3C Proteases / SARS-CoV-2 Topics: Vaccines / Variants Language: English Journal subject: Biology / Pharmacology Year: 2022 Document Type: Article Affiliation country: Md20030163

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Piperazines / Cysteine Proteinase Inhibitors / Indole Alkaloids / Coronavirus 3C Proteases / SARS-CoV-2 Topics: Vaccines / Variants Language: English Journal subject: Biology / Pharmacology Year: 2022 Document Type: Article Affiliation country: Md20030163