SARS-CoV-2 Main Protease Inhibitors from Natural Product Repository as Therapeutic Candidates for the Treatment of Coronaviridae Infections.

Curr Med Chem

Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, P.O Box 13140, Amman 11942, Jordan.

Published: November 2023

AI Article Synopsis

  • The main protease (Mpro) of SARS-CoV-2 is essential for the virus's life cycle, making it a key target for COVID-19 treatment.
  • This review focuses on natural products that have been experimentally validated as Mpro inhibitors since the COVID-19 pandemic began, classifying them by their chemical types such as flavonoids and alkaloids.
  • The identified natural compounds may be used as starting points to develop more effective and safer treatments against COVID-19.

Article Abstract

Background: The main protease (Mpro) is a crucial enzyme for the life cycle of SARS-CoV-2 and a validated target for the treatment of COVID-19 infection. Natural products have been a proper alternative for treating viral diseases by modulating different steps of the life cycle of many viruses.

Objective: This review article is designed to summarize the cumulative information of natural-derived Mpro inhibitors that are validated by experimental biological testing.

Methods: The natural-derived Mpro inhibitors of SARS-CoV-2 that have been discovered since the emergence of the COVID-19 pandemic are reviewed in this article. Only natural products with experimental validation are reported in this article. Collected compounds are classified according to their chemical identity into flavonoids, phenolic acids, quinones, alkaloids, chromones, stilbenes, tannins, lignans, terpenes, and other polyphenolic and miscellaneous natural-derived Mpro inhibitors.

Conclusion: These compounds could serve as scaffolds for further lead-structure optimization for desirable potency, a larger margin of safety, and better oral activity.

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Source
http://dx.doi.org/10.2174/0109298673271674231109052709DOI Listing

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Article Synopsis
  • The main protease (Mpro) of SARS-CoV-2 is essential for the virus's life cycle, making it a key target for COVID-19 treatment.
  • This review focuses on natural products that have been experimentally validated as Mpro inhibitors since the COVID-19 pandemic began, classifying them by their chemical types such as flavonoids and alkaloids.
  • The identified natural compounds may be used as starting points to develop more effective and safer treatments against COVID-19.
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The main protease (M ) is an essential enzyme for the life cycle of SARS-CoV-2 and a validated target for treatment of COVID-19 infection. Structure-based pharmacophore modeling combined with QSAR calculations were employed to identify new chemical scaffolds of M inhibitors from natural products repository. Hundreds of pharmacophore models were manually built from their corresponding X-ray crystallographic structures.

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