The human immunodeficiency virus t ype 1(HIV -1)envelope glycoprotein gp41plays a critical r ole in the fusion of viral and target c ell membranes.The gp41extracellular d omain,which contains fusion peptide(FP),N -and C -terminal hydrophobic hept ad repeats(NHR and CHR,respectively).Peptides derived from NHR and CHR re gions,designated N -and C -peptides,respectively,can interact with each other to form a six -stranded coiled -coil domain,representing the fu-sion -active gp41core.Our previous studies demonstrated that the C -peptides have potent inhibitory a ctivity against HIV -1infection.These peptides inhibit HIV -1-media ted membrane fusion by binding to NHR regions for preventing the formation of fusion -active gp41core.One of the C -peptides,T -20,which is in the phase III clini-cal trails,is expected to become the first peptide HIV fusion inhibitory drug in the near future.However,thi s peptide HIV fusion inhibitor lacks oral availability and is sensitive to the proteolytic digestion.Therefore,it is essential to develo p small molecular non -peptide HIV fusion inhibitors having similar me chanism of action as the C -pep-tides.We have established an ELISA -based screening assay using a unique monoclonal antibody,NC -1,w hich can specifically bind to a conformational epitope on the gp41c ore domain.Using this screening assay,we have identified a small molecular anti -HIV -1compound,named ADS -J1,which inhibits HIV -1-mediated membrane fusion by blocking the interaction between the NHR and CHR regions to form the fusion -active gp41core.This co mpound will be used as a lead to design and develop novel HIV fusion i nhibitors as new drugs for the treatment of HIV infection and /or AIDS. The human immunodeficiency virus t ype 1 (HIV-1) envelope glycoprotein gp41plays a critical r ole in the fusion of viral and target cells. The gp41 extracellular domain, which contains fusion peptide (FP), N-and C-terminminal hydrophobic hept ad repeats (NHR and CHR, respectively). Peptides derived from NHR and CHR re gions, respectively N-and C -peptides, respectively, can interact with each other to form a six-stranded coiled-coil domain, sion-active gp41core.Our previous studies demonstrated that the C -peptides have potent inhibitory a ctivity against HIV-1 infection. The peptides inhibit HIV-1-media ted membrane fusion by binding to NHR regions for preventing the formation of fusion-active gp41core. One of the C -peptides, T -20, which is in the phase III clini-cal trails, is expected to become the first peptide HIV fusion inhibitory drug in the near future. Host, thi s peptide HIV fusion inhibitor lacks oral availability and is sensitive to the proteolytic dige it is essential to develo p small molecular non-peptide HIV fusion inhibitors having similar me chanism of action as the C -pep-tides. We have established an ELISA-based screening assay using a unique monoclonal antibody, NC -1 , w hich can specifically bind to a conformational epitope on the gp41c ore domain. Using this screening assay, we have identified a small molecular anti-HIV-1 compound, named ADS-J1, which inhibits HIV-1-mediated membrane fusion by blocking the interaction between the NHR and CHR regions to form the fusion-active gp41 core. this co mpound will be used as a lead to design and develop novel HIV fusion i nhibitors as new drugs for the treatment of HIV infection and / or AIDS.