Molecular chaperones in COVID-19 pathogenesis: viral life cycle, immunity and inflammation

Chaperone machinery is an essential part of the protein quality-control system. However, viral invasion makes it a double-edged sword. On the one hand, chaperones maintain cellular proteostasis during viral replication, protect cells from apoptosis, and facilitate immune response. On the other hand, viruses can hijack the chaperoning system and employ its functions for viral propagation. They exploit chaperones for viral proteins assembly and modulation of signaling pathways to weaken the antiviral response and avoid apoptosis of infected cells. The significant role of chaperones in immunity suggests their involvement into COVID-19 pathogenesis, since hyperinflammatory reaction is a major indicator of disease’s severity. Therefore, it appears important to discuss the functions of the chaperoning system within the framework of COVID-19. In this narrative review, we summarize the mechanisms of SARS-CoV-2 and host chaperoning system interactions, explore chaperones’ involvement in antiviral immune response and a severe COVID-19 course, and address the issue of chaperone therapy in COVID-19. Databases searched include Google Scholar, PubMed, Web of Science, bioRxiv, medRxiv, and ResearchGate. The review compiles direct mechanisms and hypothetical evidence of chaperones’ involvement in COVID-19, providing the broadest insight into this issue. In practical terms, this review offers possible targets for novel diagnostic and therapeutic strategies.