Targeting the SARS-CoV-2 S-protein binding to the ACE2 receptor to preserve human cardiac pericytes function in COVID-19

Cardiovascular disease represents both a risk factor and a complication of COronaVIrus Disease 19 (COVID-19) caused by SARS-Coronavirus-2 (SARS-CoV-2).

While the increased frailty of cardiovascular patients may account for the susceptibility to infection and organ damage, the causative relation between COVID-19 and cardiac complications is less obvious. SARS-CoV-2 has adopted a successful tactic to infect, damage, and spread.

It uses a cellular receptor, the angiotensin converting enzyme 2 (ACE2), not only to enter cells but also to activate the MAPK signalling pathway, instrumental to viral replication and cellular damage.

ACE2 exerts important cardiovascular protection and, according to recent transcriptomic studies, is highly expressed by cardiac pericytes.

It has been therefore suggested that cardiac pericytes - essential cells in the maintenance of microvascular homeostasis – may represent a special target for SARS-CoV-2 infection.

Alternatively, since viral replication in the heart has not been demonstrated, circulating viral capsid proteins may be responsible for induction of signalling pathways downstream to the ACE2 receptor.

We hypothesize that engagement of the capsid S-protein to the ACE2 receptor causes ACE2 degradation thereby resulting in cardiac pericyte dysfunction.

The proposed project will investigate underpinning mechanisms downstream to the ACE2 receptor and therapeutic approaches aiding pericyte viability and