Treatment with an HSF1 degrader halts HCMV replication and spread
San Diego, March 03, 2025 – Scientists at SUNY Upstate
Medical University in Syracuse, New York, have uncovered a breakthrough
antiviral strategy against human cytomegalovirus (HCMV). Their study, published
in Antiviral Research (https://doi.org/10.1016/j.antiviral.2025.106150 demonstrates
that treatment with Sisu Pharma’s drug, a selective degrader of the stress-response
protein Heat Shock Factor 1 (HSF1), sharply reduces HCMV replication both in
vitro and in vivo.
HCMV is a widespread pathogen (60–90% prevalence among
adults) that poses severe and life-threatening risks to immunocompromised
patients and newborns. Existing antiviral drugs suffer from toxicity, limited
effectiveness, and the development of viral resistance. Dr. Gary Chan’s team at
Upstate Medical University discovered that HCMV exploits human HSF1 in infected
cells to activate and sustain its replication program. Treatment with the HSF1
degrader SISU-102, either before or after infection, blocked multiple stages of
the viral infectious cycle, slashing viral gene expression and progeny virus
production.
In a human skin xenograft mouse model, SISU-102 strongly reduced
viral replication at the initial site of infection and prevented dissemination
to distant tissues, results that compared favorably to current standard-of-care
antivirals, but with no observed side effects. Importantly, the drug retained
activity against drug-resistant HCMV strains, underscoring its therapeutic
potential. This work shows that HSF1 is a critical host factor for HCMV, and
that targeting it with a small molecule HSF1 degrader opens the door to an
exciting new class of host-directed antivirals.
The findings highlight the potential of HSF1 degraders not
only for HCMV but for a wider range of viral pathogens known to rely on HSF1
such as SARS-Cov2, as well as in oncology, where HSF1 is essential for cancer
cell survival.
About Sisu
Sisu Pharma (www.sisupharma.com)
is a biotechnology company focused on exploiting cellular stress by directly
targeting Heat Shock Factor 1 (HSF1), the central cellular stress protective
transcription factor. The company’s HSF1 targeting platform has delivered
selective HSF1 degraders for oncology that demonstrate compelling efficacy in
therapy-resistant cancer models. The company is at the forefront of developing
innovative treatments for viral infections, targeting stress-response
mechanisms to address some of the world’s most pressing health challenges.
Sisu’s technology provides additional opportunities for developing treatments
for neurodegenerative conditions.
