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

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., M^Pro and PL^Pro) 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.

Communicated by Ramaswamy H. Sarma

Keywords:

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

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. (G:533-142-1442). The authors, therefore, acknowledge with thanks DSR for technical and financial support.