Investigation of the role of heat shock proteins in the regulation of target molecules associated with SARS-COV-2

Coronaviruses are RNA viruses that are common in humans and other mammals and can cause systemic disorders.It uses Angiotensin Converting Enzyme-2 (ACE2) as a receptor for entry into the cell.In addition, TMPRSS2 and EMMPRIN (CD147) are also known to help the virus enter the cell.Endothelial cells containing ACE2 and TMPRSS2, as well as TMPRSS11D, Cyclophylline A (CYPA), CD26 and CD147, have become targets by SARS-CoV-2.As the virus enters, the cell synthesizes heat shock proteins (Hsp) to protect cellular mechanisms from damage.In particular, Hsp70 and Hsp90 are known to be highly expressed.Under hyperthermic conditions, the molecular mechanism of action of Quercetin and 17AAG, which are inhibitors Hsp70 and Hsp90, has not been fully investigated in endothelial cells.Within the scope of this study, the effects of heat shock proteins and inhibitors with increased synthesis in the cell under hyperthermic conditions on the target molecules in the cell associated with SARS-CoV-2 were investigated.Real Time PCR was performed to analyze the expression levels of HSF1, HSP90AA1, HSP90AB1, HSPA1A, ACE2, TMPRSS2, TMPRSS11D, CYPA, CD26 and CD147 genes in HUVECs treated with Quercetin and 17AAG under hyperthermic conditions.MTT and migration experiments were performed to determine the effects of quercetin and 17AAG on cell proliferation and cell migration in hyperthermia and untreated HUVECs.According to our findings, hyperthermia increased the expression levels of HSF1, HSP90AA1, HSP90AB1, HSPA1A, CYPA, CD26 and CD147 in the cells and decreased the expression levels of ACE2, TMPRSS2 and TMPRSS11D.Increased and decreased levels of these molecules with hyperthermia support the importance of hyperthermic therapy in terms of preventing the entry of SARS-CoV-2 into the cell and ensuring the continuity of endothelial cell functions.According to our other findings, 17AAG and Quercetin were found to suppress cell proliferation and migration in both hypertemic and non-hypertemic cells.