Nopporn CHUTIWITOONCHAI1,2,Takafumi MANO2, Michinori KAKISAKA2, Lowela SIAROT2, Hirotaka SATO2, Yoko AIDA2
1Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology, Thailand
2Viral Infectious Diseases Unit, The Institute of Physical and Chemical Research, Japan
Abstract
Influenza virus and human immunodeficiency virus type 1 (HIV-1) infections remain global public health problems and need to be monitored/controlled carefully. Only one class of anti-influenza drug targeting viral neuraminidase is clinically available while several drug classes against HIV-1 are approved and used in combination for therapy. However, an emergence of drug resistant virus has been reported reminding a requirement of new anti-viral drug development.
In this study, we compared the nuclear export function of influenza viral proteins and selected nucleoprotein (NP) as a target for screening of a new class anti-viral drug. Molecular mechanism of inhibition was verified indicating the hit compound inhibited viral NP and host CRM1 interaction thereby affecting viral nuclear export and replication. In addition, a novel interaction of viral NP and host NXT1 in the nuclear export pathway was identified, which can be used as a new target for drug discovery. For HIV-1, we focused on the viral assembly/budding step, which is initiated by the interaction between viral Gag and host TSG101. Targeting Gag-TSG101 interaction by the hit compounds reduced virus-like particle production and replication. Altogether, our study demonstrates promising targets for further development of novel classes of anti-viral drug against influenza and HIV-1 infections.