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

•CQ and HCQ could modulate the ACE- 2 and cause cardiotoxic effect.•Molecular docking identified that ionic interactions are the main driving forces of the CQ and HCQ in catalytic domain of the ACE-2.•In molecular dynamics was observed that the stability of the ionic interactions were present in the R-conformers of the CQ and HCQ.•This work may be helpful to better understand the cardiotoxic effects attributed to aminoquinoline drugs. 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. [Display omitted]