Aloin A inhibits SARS CoV-2 replication by targeting its binding with ACE2 - evidence from modeling-supported molecular dynamics simulation

Hani A. Alhadrami, Ahmed M. Sayed*, Hossam M. Hassan, Mostafa E. Rateb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The current study aimed to expand on the recently published results and assess the inhibitory efficacy of aloin A against SARS CoV-2. In vitro testing of aloin A against SARS CoV-2 proteases (i.e., MPro and PLPro) showed weak to moderate activity (IC50 = 68.56 ± 1.13 µM and 24.77 ± 1.57 µM, respectively). However, aloin A was able to inhibit the replication of SARS CoV-2 in Vero E6 cells efficiently with an IC50 of 0.095 ± 0.022 µM. Depending on the reported poor permeability of aloin A alongside its insignificant protease inhibitory activities presented in this study, we ran a number of extensive virtual screenings and physics-based simulations to determine the compound's potential mode of action. As a result, RBD-ACE2 was identified as a key target for aloin A. Results from 600 ns-long molecular dynamics (MD) simulation experiments pointed to aloin A's role as an RBD-ACE2 destabilizer. Therefore, the results of this work may pave the way for further development of this scaffold and the eventual production of innovative anti-SARS CoV-2 medicines with several mechanisms of action.

Original languageEnglish
JournalJournal of Biomolecular Structure & Dynamics
Early online date8 Feb 2023
DOIs
Publication statusE-pub ahead of print - 8 Feb 2023

Keywords

  • SARS CoV-2
  • MPro
  • PLPro
  • RBD-ACE2
  • molecular dynamics simulation
  • virtual screening

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