A synthesized or isolated influenza virus replication-inhibiting peptide that competitively inhibits protein-protein interaction of the PA and PB1 of both influenza Virus Types A and B and novel in vitro binding screen to identify peptides with antiviral activity against influenza viruses of both type A and B is disclosed. In addition to the well-known pandemic influenza A viruses (such as the 1918 “Spanish” flu or H5N1), both type A and B viruses contribute greatly to the annual recurring epidemics that cause the vast majority of human cases and medical cost. Surprisingly, it was found that the novel virus replication-inhibiting, are able to inhibit protein-protein interaction of the PA and PB1 subunits of the heterotrimeric viral RNA polymerase complex of both influenza virus types A and B. The viral polymerase sub-unit interaction domain turned out as an effective target for the new antivirals, as correct assembly of the three viral polymerase subunits PB1, PB2 and PA is required for viral RNA synthesis and infectivity.
