EIDD-3525 is a broad-spectrum antiviral against alphavirus infection that targets the nsP4 RNA-dependent RNA polymerase
- 1University of Colorado Denver
Abstract
Mosquito-transmitted alphaviruses, including chikungunya (CHIKV), Mayaro, Eastern equine encephalitis, and Venezuelan equine encephalitis viruses, cause severe arthritic or neurologic disease in humans. There are currently no approved antiviral treatments against alphavirus infection. Here, we report that the purine ribonucleoside EIDD-3525 is a potent inhibitor of alphavirus replication in vitro with broad spectrum antiviral activity against the Alphavirus genus. Using a trans-replicase assay, we find that EIDD-3525 blocks alphavirus RNA replication. Mutational profiling suggests that EIDD-3525 targets the alphavirus nsP4 RNA-dependent RNA polymerase that is conserved across medically important alphaviruses. In a pre-clinical mouse model of CHIKV infection and disease, oral treatment with EIDD-3525 reduced viral tissue burdens and the severity of virus-induced disease. Collectively, our findings support the continued development of the purine ribonucleoside EIDD-3525 as an orally available antiviral therapeutic for use against a broad group of alphaviruses.
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BibTeX
@misc{yin2026eidd3525,
title = {{EIDD-3525 is a broad-spectrum antiviral against alphavirus infection that targets the nsP4 RNA-dependent RNA polymerase}},
author = {P. Yin and S. Choudhary and S. Wang and B. J. Davenport and P. M. Truong and Z. M. Sticher and R. Krueger and A. A. Cruz and M. Smith and A. A. Kolykhalov and D. Vyshenska and A. L. Greninger and S. Mao and M. G. Natchus and G. R. Painter and A. Merits and M. Kielian and T. E. Morrison},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.26.754626},
url = {https://www.biorxiv.org/content/10.64898/2026.09.26.754626v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - EIDD-3525 is a broad-spectrum antiviral against alphavirus infection that targets the nsP4 RNA-dependent RNA polymerase
AU - P. Yin
AU - S. Choudhary
AU - S. Wang
AU - B. J. Davenport
AU - P. M. Truong
AU - Z. M. Sticher
AU - R. Krueger
AU - A. A. Cruz
AU - M. Smith
AU - A. A. Kolykhalov
AU - D. Vyshenska
AU - A. L. Greninger
AU - S. Mao
AU - M. G. Natchus
AU - G. R. Painter
AU - A. Merits
AU - M. Kielian
AU - T. E. Morrison
PY - 2026
DA - 2026/09/26
PB - bioRxiv
DO - 10.64898/2026.09.26.754626
UR - https://www.biorxiv.org/content/10.64898/2026.09.26.754626v1
AB - Mosquito-transmitted alphaviruses, including chikungunya (CHIKV), Mayaro, Eastern equine encephalitis, and Venezuelan equine encephalitis viruses, cause severe arthritic or neurologic disease in humans. There are currently no approved antiviral treatments against alphavirus infection. Here, we report that the purine ribonucleoside EIDD-3525 is a potent inhibitor of alphavirus replication in vitro with broad spectrum antiviral activity against the Alphavirus genus. Using a trans-replicase assay, we find that EIDD-3525 blocks alphavirus RNA replication. Mutational profiling suggests that EIDD-3525 targets the alphavirus nsP4 RNA-dependent RNA polymerase that is conserved across medically important alphaviruses. In a pre-clinical mouse model of CHIKV infection and disease, oral treatment with EIDD-3525 reduced viral tissue burdens and the severity of virus-induced disease. Collectively, our findings support the continued development of the purine ribonucleoside EIDD-3525 as an orally available antiviral therapeutic for use against a broad group of alphaviruses.
ER -