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

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 and PL) showed weak to moderate activity (IC = 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 IC 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.