Baloxavir marboxil, a novel cap-dependent endonuclease inhibitor potently suppresses influenza virus replication and represents therapeutic effects in both immunocompetent and immunocompromised mouse models

• DOI: 10.1371/journal.pone.0217307
• Publication Date: 2019-05-20T17:31:13Z
• Authors: Keita Fukao; Yoshinori Ando; Takeshi Noshi; Mitsutaka Kitano; Takahiro Noda; Makoto Kawai; Ryu Yoshida; Akihiko Sato; Takao Shishido; Akira Naito
• Keywords: Oseltamivir

Baloxavir marboxil (BXM) is an orally available small molecule inhibitor of cap-dependent endonuclease (CEN), essential enzyme in the initiation mRNA synthesis influenza viruses. In present study, we evaluated efficacy BXM against virus infection mouse models. Single-day oral administration completely prevented mortality due to with A and B mice. Moreover, 5-day repeated was more effective for reducing body weight loss mice infected than oseltamivir phosphate (OSP), even when treatment delayed up 96 hours post (p.i.). Notably, BXM, starting at 72 p.i. led significant decrease titers >2-log10 reduction compared vehicle control within 24 after administration. Virus lung significantly greater that observed OSP. addition, profound sustained titer immunocompromised model without emergence variants possessing treatment-emergent amino acid substitutions target protein. our immunocompetent models, resulted rapid potent infectious prevention signs infection, suggesting could extend therapeutic window patients regardless host immune status.