Verdinexor is a potent and selective SINE inhibitor, shown to be effective in treating influenza A virus infection in mice and ferret models.
verdinexor (kpt-335) is a potent and selective inhibitor of nuclear export [1].nuclear export (sine) is mainly mediated by exportin 1 (xpo1) and mediates specific proteins out of the nucleus, which plays an important role in the regulation of proliferation and the cell cycle [2].verdinexor (kpt-335) is a potent and selective sine inhibitor that acts as an antiviral drug. in a549 cells inoculated with the influenza a and b virus, verdinexor effectively inhibited the replication of the influenza a and b virus strains tested. verdinexor (1 μm) caused the accumulation of vrnps in the nuclei and altered the localization of viral ns1. also, verdinexor increased nuclear negative-sense vrna by 56.6-fold and significantly reduced cytoplasmic negative-sense vrna, which suggested that verdinexor blocked vrnp nuclear export. in 293t cells, verdinexor inhibited xpo1-nep binding [1].in mice infected with influenza virus a, verdinexor significantly reduced lung influenza virus a titers. verdinexor also reduced the expression of proinflammatory cytokines tumor necrosis factor alpha, interleukin-6, interleukin-1β and gamma interferon. in mice infected with a lethal dose, verdinexor inhibited virus penetration of the respiratory tract and virus spread in the lungs [1]. in companion dogs with b- and t-cell lymphomas, verdinexor showed potent cytotoxic activity [2].
[1]. perwitasari o, johnson s, yan x, et al. verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo. j virol, 2014, 88(17): 10228-10243.
[2]. gravina gl, senapedis w, mccauley d, et al. nucleo-cytoplasmic transport as a therapeutic target of cancer. j hematol oncol, 2014, 7: 85.
