The present invention relates to the identification of host cell proteins that interact with viral proteins required for virus replication, and high throughput assays to identify compounds that interfere with the specific interaction between the viral and host cell protein. Interfering compounds that inhibit viral replication can be used therapeutically to treat viral infection. The invention is based, in part, on the Applicants' discovery of novel interactions between viral proteins and a human host cell proteins. One of these host cell proteins, referred to herein as NPI-1, interacts with influenza virus protein NP. Also, host cell proteins, referred to herein as NS1I-1 and NS1-BP interact with influenza virus protein NS.sub.1. In addition, host cell proteins containing WW domains that interact with viral proteins such as Rhabdoviral M protein are described. Compounds that interfere with the binding of the host cell and viral proteins, and inhibit viral replication can be useful for treating viral infection in vivo.