Olive-Derived Triterpenes Suppress SARS COV-2 Main Protease: A Promising Scaffold for Future Therapeutics.

Hani A Alhadrami,Ahmed M Sharif,Mostafa E Rateb,Ahmed M Sayed,Esam I Azhar

doi:10.3390/molecules26092654

Hani A Alhadrami, Ahmed M Sharif + Show 3 more

Open Access

https://doi.org/10.3390/molecules26092654

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Abstract

SARS CoV-2 pandemic is still considered a global health disaster, and newly emerged variants keep growing. A number of promising vaccines have been recently developed as a protective measure; however, cost-effective treatments are also of great importance to support this critical situation. Previously, betulinic acid has shown promising antiviral activity against SARS CoV via targeting its main protease. Herein, we investigated the inhibitory potential of this compound together with three other triterpene congeners (i.e., ursolic acid, maslinic acid, and betulin) derived from olive leaves against the viral main protease (Mpro) of the currently widespread SARS CoV-2. Interestingly, betulinic, ursolic, and maslinic acids showed significant inhibitory activity (IC50 = 3.22–14.55 µM), while betulin was far less active (IC50 = 89.67 µM). A comprehensive in-silico analysis (i.e., ensemble docking, molecular dynamic simulation, and binding-free energy calculation) was then performed to describe the binding mode of these compounds with the enzyme catalytic active site and determine the main essential structural features required for their inhibitory activity. Results presented in this communication indicated that this class of compounds could be considered as a promising lead scaffold for developing cost-effective anti-SARS CoV-2 therapeutics.

Highlights

Severe acute respiratory syndrome caused by the enveloped virus coronavirus-2 (SARS CoV-2) is still a worldwide health disaster despite the recently introduced vaccines [1,2]
Results presented in this communication indicated that this class of compounds could be considered as a promising lead scaffold for developing cost-effective anti-SARS CoV-2 therapeutics
main protease (Mpro) of coronaviruses occur in a dimeric form (Figure 1C), and their catalytic activity significantly decreases if this conserved dimerization is inhibited by mutations [6,7]

Summary

Introduction

Severe acute respiratory syndrome caused by the enveloped virus coronavirus-2 (SARS CoV-2) is still a worldwide health disaster despite the recently introduced vaccines [1,2]. Finding a cost-effective treatment is an urgent demand to support vaccines in controlling this rapidly evolving disease. The viral main protease (Mpro) is able to recognize and cleave specific amino acid sequences in the viral polyprotein replication complex (1ab). It is a highly conserved protein among coronaviruses [3], and it is considered an attractive target for the development of effective and specific therapeutics [4,5].

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