In a pathbreaking study, Jawaharlal Nehru University (JNU) scientists Dr Anand Ranganathan, Professor Shailja Singh and their team including Russian researchers have found that human protein hsp70 can be crucial in the treatment of COVID-19 and Malaria.
The researchers developed a small molecule Hsp70 inhibitor that could be used to treat a multitude of infections. Notably, Hsp70 (Heat Shock Protein 70) is a molecular chaperone or a protein that aids in the proper folding of other proteins and blocks misfolding.
Published in the prestigious International Journal of Biological Macromolecules, the study, led by Dr Anand Ranganathan and Shailja Singh of JNU’s Special Centre for Molecular Medicine, reveals that targeting Hsp70 could help prevent drug resistance, which is becoming a major issue in infection treatment.
“Here, for the first time, we demonstrate that the SARS-CoV-2 exploits the host Heat shock protein 70 (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 expression in host Vero E6 cells. Furthermore, heat shock or viral infection elevates the host cell autophagic response which is a prerequisite for viral propagation,” the research paper titled Targeting host inducible-heat shock protein 70 with PES-Cl is a promising antiviral strategy against SARS-CoV-2 infection and pathogenesis states.
The researchers observed that Hsp70 interacts with the spike protein of SARS-CoV-2, the virus that causes COVID-19, and human ACE2 receptors, which the virus uses to enter cells.
“In addition, Hsp70 protein demonstrated strong interaction with host Angiotensin-converting enzyme 2 (ACE2) as well as the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein, indicating that interaction of Hsp70 with ACE2 and Spike protein may serve to protect them during febrile conditions,” the study says.
In their research, Dr Ranganathan and the team hypothesised that fever raises Hsp70 levels, which helps stabilise this interaction and allows the virus to infect cells more easily. In lab testing, blocking Hsp70 successfully prevented viral replication. This host-targeting method has several advantages as contrary to traditional medications that target the virus, host-targeting antivirals are less likely to develop resistance since the virus cannot change the host protein. This approach may be especially successful against quickly developing viruses like SARS-CoV-2 and its derivatives.
The researchers concluded that the 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.”
