安全なバイオセーフティレベル2システムを用いたエボラウイルス阻害剤としてのゲムシタビンの同定

The Lassa virus (LASV), a member of the Old World arenaviruses and classified as a risk-group 4 pathogen, causes severe hemorrhagic fever in humans with significant mortality. Here, we developed a robust LASV reverse genetics system designated LASV_sg that models the complete LASV life cycle under biosafety level-2 (BSL-2) conditions. Using this system, we screened a library of nucleoside/nucleotide analogs for anti-LASV activity. Gemcitabine, a clinically approved nucleoside analog, was identified to exhibit pronounced antiviral efficacy against LASV_sg, which was further confirmed using authentic LASV in a BSL-4 laboratory. Mechanistic analyses revealed that gemcitabine suppresses LASV infection by reducing viral protein levels without directly inhibiting viral RNA replication or transcription. In summary, we developed a robust BSL-2 reverse genetics system for LASV research, enabling the identification of gemcitabine as a potential antiviral candidate.