PEPTIDES FROM CONSERVED REGIONS OF PARAMYXOVIRUS FUSION (F)-PROTEINS ARE POTENT INHIBITORS OF VIRAL FUSION

The synthetic peptides DP-107 and DP-178 (T-20), derived from separate domains within the human immunodeficiency virus type 1 (HIV-1) transm embrane (TM) protein, gp41, are stable and potent inhibitors of HIV-1 infection and fusion, Using a computer searching strategy (computerize d antiviral searching technology, C.A.S.T.) based on the predicted sec ondary structure of DP-107 and DP-178 (T-20), we have identified conse rved heptad repeat domains analogous to the DP-107 and DP-178 regions of HIV-1 gp41 within the glycoproteins of other fusogenic viruses, Her e we report on antiviral peptides derived from three representative pa ramyxoviruses, respiratory syncytial virus (RSV), human parainfluenza virus type 3 (HPIV-3), and measles virus (MV). We screened crude prepa rations of synthetic 35-residue peptides, scanning the DP-178-like dom ains, in antiviral assays. Peptide preparations demonstrating antivira l activity were purified and tested for their ability to block syncyti um formation, Representative DP-178-like peptides from each paramyxovi rus blocked homologous virus-mediated syncytium formation and exhibite d EC(50) values in the range 0.015-0.250 mu M. Moreover, these peptide s were highly selective for the virus of origin, Identification of bio logically active peptides derived from domains within paramyxovirus F- 1 proteins analogous to the DP-178 domain of HIV-1 gp41 is compelling evidence for equivalent structural and functional features between ret roviral and paramyxoviral fusion proteins. These antiviral peptides pr ovide a novel approach to the development of targeted therapies for pa ramyxovirus infections.