Antiviral activity of HSP90 inhibitors against Mumps virus and related paramyxoviruses
Abstract
Mumps virus (MuV), a member of the family Paramyxoviridae , continues to cause recurrent outbreaks worldwide despite widespread vaccination. Currently, however, no antiviral drugs have been approved for MuV or other paramyxoviruses. In this study, we screened approximately 1,000 small-molecule compounds using a recombinant MuV expressing green fluorescent protein and identified six compounds that significantly suppressed viral replication without detectable cytotoxicity. These compounds were known inhibitors of heat shock protein 90 (HSP90), a host chaperone involved in the assembly and function of viral polymerase complexes. These HSP90 inhibitors exhibited potent antiviral activity with submicromolar EC₅₀ values and high selectivity indices. Moreover, their antiviral efficacy extended to other paramyxoviruses, including measles virus (MeV), canine distemper virus (CDV), and Sendai virus (SeV). Time-of-addition assays demonstrated that these compounds act at a post-entry stage, primarily during viral RNA synthesis. Consistently, minigenome assays of MuV and Nipah virus (NiV) confirmed robust suppression of viral RNA synthesis without direct inhibition of reporter enzyme activity, indicating target specificity. Collectively, our findings highlight the potential of HSP90 inhibitors as host-directed antiviral agents against paramyxoviruses and support their further development for the treatment of emerging and re-emerging paramyxovirus infections.
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BibTeX
@article{kato2026antiviral,
title = {{Antiviral activity of HSP90 inhibitors against Mumps virus and related paramyxoviruses}},
author = {Fumihiro Kato and Chaewon Bae and Aika Wakata and Masatoshi Kakizaki and Takashi Okura and Yuichiro Nakatsu and Fumio Seki and Kenji Someya and Noriyuki Otsuki and Akihide Ryo and Yusuke Matsumoto and Hideo Fukuhara and Katsumi Maenaka and Mari Ishigami-Yuasa and Minoru Kidokoro and Masaki Ochiai and Koji Ishii and Hiroshi Katoh and Makoto Takeda},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-76801-5},
url = {https://www.nature.com/articles/s41598-026-76801-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Antiviral activity of HSP90 inhibitors against Mumps virus and related paramyxoviruses
AU - Fumihiro Kato
AU - Chaewon Bae
AU - Aika Wakata
AU - Masatoshi Kakizaki
AU - Takashi Okura
AU - Yuichiro Nakatsu
AU - Fumio Seki
AU - Kenji Someya
AU - Noriyuki Otsuki
AU - Akihide Ryo
AU - Yusuke Matsumoto
AU - Hideo Fukuhara
AU - Katsumi Maenaka
AU - Mari Ishigami-Yuasa
AU - Minoru Kidokoro
AU - Masaki Ochiai
AU - Koji Ishii
AU - Hiroshi Katoh
AU - Makoto Takeda
PY - 2026
DA - 2026/10/27
JO - Scientific Reports
DO - 10.1038/s41598-026-76801-5
UR - https://www.nature.com/articles/s41598-026-76801-5
AB - Mumps virus (MuV), a member of the family Paramyxoviridae , continues to cause recurrent outbreaks worldwide despite widespread vaccination. Currently, however, no antiviral drugs have been approved for MuV or other paramyxoviruses. In this study, we screened approximately 1,000 small-molecule compounds using a recombinant MuV expressing green fluorescent protein and identified six compounds that significantly suppressed viral replication without detectable cytotoxicity. These compounds were known inhibitors of heat shock protein 90 (HSP90), a host chaperone involved in the assembly and function of viral polymerase complexes. These HSP90 inhibitors exhibited potent antiviral activity with submicromolar EC₅₀ values and high selectivity indices. Moreover, their antiviral efficacy extended to other paramyxoviruses, including measles virus (MeV), canine distemper virus (CDV), and Sendai virus (SeV). Time-of-addition assays demonstrated that these compounds act at a post-entry stage, primarily during viral RNA synthesis. Consistently, minigenome assays of MuV and Nipah virus (NiV) confirmed robust suppression of viral RNA synthesis without direct inhibition of reporter enzyme activity, indicating target specificity. Collectively, our findings highlight the potential of HSP90 inhibitors as host-directed antiviral agents against paramyxoviruses and support their further development for the treatment of emerging and re-emerging paramyxovirus infections.
SN - 2045-2322
ER -