2025-09-17 北海道大学
<関連情報>
- https://www.hokudai.ac.jp/news/2025/09/post-2064.html
- https://www.hokudai.ac.jp/news/pdf/250917_pr3.pdf
- https://journals.asm.org/doi/10.1128/aac.00186-25
キャップ依存性エンドヌクレアーゼ阻害剤はラクロスウイルス感染に対する抗ウイルス化合物として作用する A cap-dependent endonuclease inhibitor acts as a potent antiviral agent against La Crosse virus infection
Kei Konishi, Yoshiyuki Taoda, Manabu Igarashi, Takao Shishido, Kazuya Yasuo, William W. Hall, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki, Akihiko Sato
Antimicrobial Agents and Chemotherapy Published:23 July 2025
DOI:https://doi.org/10.1128/aac.00186-25
ABSTRACT
La Crosse virus (LACV) infection, the causative agent of La Crosse encephalitis, can lead to severe neurological symptoms and sequelae, particularly in children. Despite annual reports of neurologically symptomatic cases, no effective treatment has yet been established. Bunyaviruses, including LACV, utilize a cap-snatching mechanism for transcription, with a cap-dependent endonuclease (CEN) serving as a promising target for antiviral treatment. Specifically, we now demonstrate that a CEN inhibitor, carbamoyl pyridone carboxylic acid (CAPCA)-1, exhibits potent anti-LACV activity in vitro and in vivo. CAPCA-1 exhibited 50% effective concentration values below 1 µM in neuronal and non-neuronal cells, demonstrating a higher in vitro activity than the nucleoside analogs, ribavirin and favipiravir. Multiple passages of LACV in the presence of CAPCA-1 produced numerous amino acid mutations in the CEN active site. Notably, using a lethal infection model in mice, CAPCA-1 treatment reduced viral loads in the brain and extended the survival rate of LACV-infected mice. These findings highlight the potential of CEN inhibitors as treatment options for La Crosse encephalitis.
