TY - JOUR
T1 - Harnessing PROTACs to combat H5N1 influenza
T2 - A new frontier in viral destruction
AU - Mukerjee, Nobendu
AU - Maitra, Swastika
AU - Mukherjee, Dattatreya
AU - Ghosh, Arabinda
AU - Alexiou, Athanasios T.
AU - Thorat, Nanasheb D.
N1 - Publisher Copyright:
© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.
PY - 2024/9
Y1 - 2024/9
N2 - H5N1, a highly pathogenic avian influenza virus, poses an ongoing and significant threat to global public health, primarily due to its potential to cause severe respiratory illness and high mortality rates in humans. Despite extensive efforts in vaccination and antiviral therapy, H5N1 continues to exhibit high mutation rates, resulting in recurrent outbreaks and the emergence of drug-resistant strains. Traditional antiviral therapies, such as neuraminidase inhibitors and M2 ion channel blockers, have demonstrated limited efficacy, necessitating the exploration of innovative therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) emerge as a novel and promising approach, leveraging the ubiquitin-proteasome system to selectively degrade pathogenic proteins. Unlike conventional inhibitors that only block protein function, PROTACs eliminate the target protein, providing a sustained therapeutic effect and potentially reducing the development of resistance. This paper offers a comprehensive examination of the current landscape of H5N1 infections, detailing the pathogenesis and challenges associated with existing treatments. It further explores the mechanism of action, design, and therapeutic potential of PROTACs in inhibiting H5N1. By targeting essential viral proteins, such as hemagglutinin and the RNA-dependent RNA polymerase complex, PROTACs hold the potential to revolutionize the treatment of H5N1 infections, offering a new frontier in antiviral therapy.
AB - H5N1, a highly pathogenic avian influenza virus, poses an ongoing and significant threat to global public health, primarily due to its potential to cause severe respiratory illness and high mortality rates in humans. Despite extensive efforts in vaccination and antiviral therapy, H5N1 continues to exhibit high mutation rates, resulting in recurrent outbreaks and the emergence of drug-resistant strains. Traditional antiviral therapies, such as neuraminidase inhibitors and M2 ion channel blockers, have demonstrated limited efficacy, necessitating the exploration of innovative therapeutic strategies. Proteolysis-targeting chimeras (PROTACs) emerge as a novel and promising approach, leveraging the ubiquitin-proteasome system to selectively degrade pathogenic proteins. Unlike conventional inhibitors that only block protein function, PROTACs eliminate the target protein, providing a sustained therapeutic effect and potentially reducing the development of resistance. This paper offers a comprehensive examination of the current landscape of H5N1 infections, detailing the pathogenesis and challenges associated with existing treatments. It further explores the mechanism of action, design, and therapeutic potential of PROTACs in inhibiting H5N1. By targeting essential viral proteins, such as hemagglutinin and the RNA-dependent RNA polymerase complex, PROTACs hold the potential to revolutionize the treatment of H5N1 infections, offering a new frontier in antiviral therapy.
KW - H5N1 influenza
KW - PROTACs
KW - antiviral therapy
KW - protein degradation
KW - viral pathogenesis
UR - http://www.scopus.com/inward/record.url?scp=85204417331&partnerID=8YFLogxK
U2 - 10.1002/jmv.29926
DO - 10.1002/jmv.29926
M3 - Comment/debate
C2 - 39295251
AN - SCOPUS:85204417331
SN - 0146-6615
VL - 96
JO - Journal of Medical Virology
JF - Journal of Medical Virology
IS - 9
M1 - e29926
ER -