Host inducible-HSP70A1A is an irresistible drug target to combat SARS-CoV-2 infection and pathogenesis

Joshi, P.; Garg, S.; Mani, S.; Jakhar, K.; Marothia, M.; Shoaib, R.; Biswas, S.; Singhal, J.; Behl, A.; Kahlon, A. K.; Shevtsov, M.; Garg, P.; Singh, S.; Ranganathan, A.

doi:10.1101/2023.05.05.539661

bioRxiv · 10.1101/2023.05.05.539661

Host inducible-HSP70A1A is an irresistible drug target to combat SARS-CoV-2 infection and pathogenesis

Joshi, P.·Garg, S.·Mani, S.·Jakhar, K.·Marothia, M.·Shoaib, R.·Biswas, S.·Singhal, J.·Behl, A.·Kahlon, A. K.·Shevtsov, M.·Garg, P.·Singh, S.·Ranganathan, A.

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Abstract

One of the fundamental mechanisms developed by the host to contain the highly infectious and rapidly proliferating SARS coronavirus is elevation of body temperature, a natural fallout of which is Heat Shock Protein (HSP) over-expression. Here, for the first time, we demonstrate that the SARS-CoV-2 virus exploits the host Hsp70 chaperone for its entry and propagation and blocking it can combat the infection. SARS-CoV-2 infection as well as febrile temperature enhanced Hsp70 overexpression in host Vero E6 cells. In turn, Hsp70 overexpression elevated the host cell autophagic response that is a prerequisite for viral propagation. Suppressive and prophylactic treatment of Vero E6 cells with HSP70 inhibitor PES-Cl, a small molecule derivative of Pifithrin , abrogated viral infection more potently than the currently used drug Remdesivir by suppressing host HSP70 and autophagic response. In conclusion, our study not only provides a fundamental insight into the role of host Hsp70 in SARS-CoV-2 pathogenesis, it paves the way for the development of potent and irresistible anti-viral therapeutics.

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Joshi, P., Garg, S., Mani, S., Jakhar, K., Marothia, M., Shoaib, R., Biswas, S., Singhal, J., Behl, A., Kahlon, A. K., Shevtsov, M., Garg, P., Singh, S., Ranganathan, A.. 2023-05-08. Host inducible-HSP70A1A is an irresistible drug target to combat SARS-CoV-2 infection and pathogenesis. https://doi.org/10.1101/2023.05.05.539661

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