HSP60 and SARS-CoV-2: Les Liaisons Dangereuses.

Abstract

Heat shock protein 60 (Hsp60) plays a crucial role in cellular homeostasis and stress responses. Recent evidence highlights its involvement in COVID-19 pathophysiology, particularly in immune modulation, inflammation, and endothelial dysfunction. Extracellular Hsp60 can interact with Toll-like receptors, amplifying inflammatory responses and contributing to cytokine storm and tissue damage. Additionally, since the presence of several common epitopes with SARS-CoV-2 proteins, its role in molecular mimicry suggests a potential link also to post-infectious autoimmune disorders. Hsp60 has also been implicated in endothelial damage and thromboembolic complications observed in severe COVID-19 cases. Beyond its pathogenic roles, Hsp60 could emerge as a potential biomarker for disease severity as well as a target for therapeutic strategies aimed at modulating immune responses. Finally, the structural similarity with SARS-CoV-2 proteins raises important considerations regarding both vaccine safety and the unexpected potential for anti-tumor immunity. This review critically examines the multifaceted roles of Hsp60 in COVID-19, specifically from a morpho-functional point of view, highlighting its implications in disease progression, post-viral complications, and therapeutic opportunities.