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

Abstract

• 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.