Do Cellular Entry Mechanisms of SARS-Cov-2 Affect Myocardial Cells and Contribute to Cardiac Injury in COVID-19 Patients?

Abstract

Although the main vital organ affected by SARS CoV-2 is the lung, more than 20% of hospitalized patients show heart injury, however, the underlying mechanisms are still actively investigated. Inflammation or myocardial ischemia are now well-established pathogenic factors. Direct cardiac damage by the virus is likely and might account for some aspects of cardiac disease in COVID-19 patients. However, precise knowledge on mechanisms of virus entry and progression in host cells and notably in cardiac cells is necessary in order to define the broad spectrum of pathogenicity of SARS-Cov-2 on myocardium and to identify specific therapeutic targets. This review will focus on the intracellular trafficking machinery, the Achilles heel of host cells, which can be used by the virus to infect cells of the cardiovascular system.

Keywords: COVID-19; SARS-CoV-2; internalization; myocardium; trafficking.

FIGURE 1

Regulation of ACE2 expression and mechanisms of entry of SARS-CoV-2. ACE2 converts AngII (1-8) to Ang (1-7), the Mas-R receptor agonist with anti-inflammatory and anti-fibrotic effects. ACE2 can also be cleaved and become plasmatic by the ADAM17 protease, which is itself activated by the AT1-R receptor. In gray lettering are indicated the different molecules currently being studied to prevent internalization of the virus and its subsequent replication in the endoplasmic reticulum (ER).