Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 25, 2024 3 months, 4 weeks, 17 hours, 50 minutes ago
Medical News: The global fight against COVID-19 has seen various approaches to curb the spread of the SARS-CoV-2 virus. While traditional antiviral drugs focus on targeting viral proteins, these approaches often fall short as viruses quickly mutate, rendering such treatments ineffective. In a groundbreaking study, researchers from Jawaharlal Nehru University in India, NCR Biotech Science Cluster in India, Technische Universität München in Germany, the Institute of Cytology of the Russian Academy of Sciences (RAS) in Russia, and the Almazov National Medical Research Centre in Russia have identified a promising new approach that targets the host's cellular machinery instead of the virus itself. This Medical News report delves into the study's key findings, which highlight the potential of targeting Heat Shock Protein 70 (Hsp70) as a novel antiviral strategy against SARS-CoV-2.
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New antiviral strategy targets Heat Shock Protein 70 to combat COVID-19
Understanding Hsp70 and Its Role in Viral Propagation
Heat Shock Proteins (HSPs) are a group of proteins that are produced by cells in response to stressful conditions, such as elevated body temperature. Among them, Hsp70 plays a crucial role in maintaining cellular protein homeostasis by assisting in the proper folding and remodeling of proteins. However, this study reveals that SARS-CoV-2 has developed a way to exploit Hsp70 to facilitate its entry and propagation within host cells.
When a person is infected with SARS-CoV-2, the virus triggers a febrile response, leading to increased body temperature and the overexpression of Hsp70 in host cells. The study found that this overexpression is not just a byproduct of infection but a deliberate strategy by the virus to enhance its survival. By interacting with the host's Angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, Hsp70 helps protect these crucial components during the infection, thereby aiding the virus in entering and replicating within host cells.
The Autophagy Connection
Autophagy, a cellular process where cells degrade and recycle their own components, is another critical pathway that the SARS-CoV-2 virus hijacks for its replication. The study demonstrated that the overexpression of Hsp70 due to viral infection or heat shock also elevates the host cell's autophagic response. This autophagic response is essential for the virus, as it provides a conducive environment for its replication. The study found that SARS-CoV-2 induces the formation of double-membrane vesicles (DMVs), which are required for the congregation of viral replication and transcriptional machinery. These DMVs are closely linked with autophagosomes, the vesicles involved in autophagy, suggesting that the virus uses the host's autophagic machinery to shield its replication process from cellular defense mechanisms.
PES-Cl: A Promising Inhibitor
In the quest to find an effective treatment against COVID-19, the researchers explored the potential of PES-Cl, a small molecule inhibitor known to target the substrate-binding domain of Hsp70. This study found that PES-Cl was more effective than the widely used antiviral drug Rem
desivir in inhibiting the replication of SARS-CoV-2 in infected cells. Specifically, PES-Cl disrupted the interaction between Hsp70 and the ACE2 receptor, as well as the viral spike protein, thereby blocking the virus's entry into host cells.
Thailand Medical News would like to add that besides, PEES-CI, there are a number of naturally occurring phytochemicals from well-known herbs that can also be used to target the Hsp70 molecule.
Moreover, PES-Cl treatment led to a significant reduction in autophagy markers, effectively curbing the autophagic response that the virus relies on for its propagation. This dual action of PES-Cl - disrupting viral entry and hindering the autophagic pathway - makes it a particularly potent antiviral agent against SARS-CoV-2.
Key Study Findings
The study's findings provide a fundamental insight into the role of host Hsp70 in SARS-CoV-2 pathogenesis. By demonstrating that the inhibition of Hsp70 can abrogate viral infection more effectively than current treatments, the research paves the way for the development of new antiviral therapeutics that target the host's cellular machinery rather than the virus itself.
The study also highlights the potential of PES-Cl as a broad-spectrum antiviral agent. Unlike traditional antivirals that target viral proteins and are prone to resistance due to rapid viral mutations, targeting a highly conserved host protein like Hsp70 offers a more stable and resilient approach to antiviral therapy. The research suggests that by inhibiting Hsp70, it is possible to prevent the virus from exploiting the host's cellular pathways, thereby reducing viral load and the severity of the infection.
Conclusion
The findings from this study mark a significant advancement in the fight against COVID-19. Targeting Hsp70 as an antiviral strategy offers a promising alternative to traditional therapies, which often struggle with the challenge of viral mutations and resistance. By disrupting the virus's ability to exploit the host's cellular machinery, PES-Cl emerges as a potent candidate for future antiviral drugs.
As we continue to seek effective treatments for COVID-19 and prepare for potential future pandemics, the strategy of targeting host proteins like Hsp70 could become an essential tool in our antiviral arsenal.
The study findings were published in the peer-reviewed International Journal of Biological Macromolecules.
https://www.sciencedirect.com/science/article/abs/pii/S0141813024058756
An earlier preprint version of the study is available for free here:
https://www.biorxiv.org/content/10.1101/2023.05.05.539661v1.full.pdf
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