HDN2398 is a broad-spectrum influenza inhibitor that blocks multiple functions of viral NS1 protein, exhibits H1N1virusA/ Virginia/ATCC1/2009 inhibition (IC50=3.3 uM) in MDCK cells.
HDN2398 significantly reduced the virus titer and plaque formation in A/Puerto Rico/8/34 (PR/8)-, A/Aichi/2/1968 (Aichi)-, and A/Virginia/ATCC1/2009 (Vir09)-infected cells in a dose-dependent manner, with IC50 values ranging from 2.6 to 7.7μM, which was superior to the effects of oseltamivir.
HDN2398 (2.5 or 5mg/kg/day, oral) significantly decreased pulmonary viral titers in mouse pneumonia model.
HDN2398 (25 µM) can markedly protect virus NS1 rather than NA protein from protease digestion especially under pronase treatment at 6μg/ml.
HDN2398 blocks the nuclear export of NS1 by interfering with its binding to nucleolin.
HDN2398 affects the mRNA splicing and nuclear export by blocking the binding of NS1 to NS1-BP and NXF1.
HDN2398 attenuates the interferon antagonistic function of NS1 by reducing the NS1-dsRNA interaction and the ubiquitination of RIG-I.