Evaluation of chloroquine and hydroxychloroquine as ACE-2 Inhibitors By In Silico Approaches: Cardiac Arrhythmia Cause?

Chloroquine and hydroxychloroquine impair in vitro the terminal glycosylation of angiotensin-converting enzyme 2 (ACE-2), which is known to be cardioprotective. As these aminoquinoline antimalarials are associated with cardiovascular effects, details of their molecular basis on human ACE-2 inhibition still need moving forward with scientific information. Here, molecular docking and dynamics were applied to promote molecular understanding of the antimalarial isomers interactions with human ACE-2. We identified by docking that ionic interactions are the main driving forces. In molecular dynamics, it was observed that the stability of these interactions were present only in R-conformers. These findings may be helpful to better understand the cardiotoxic effects attributed to drugs with the potential to modulate human ACE-2. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

Chloroquine and hydroxychloroquine have been found to inhibit the terminal glycosylation of angiotensin-converting enzyme 2 (ACE-2) in vitro, potentially leading to a decrease in cardioprotective function. The main driving force of the interaction between these drugs and ACE-2 was identified to be ionic interactions, with stability only present in specific conformers. This molecular understanding may help to explain the cardiotoxic effects associated with drugs that modulate human ACE-2.