Inhibition of HIV-1-Induced Cytopathogenicity, Syncytium Formation, and Virus-Cell Binding by Naphthalenedisulphonic Acids through Interaction with the Viral Envelope gp120 Glycoprotein

Bis-naphthalenedisulphonic acid derivatives with a biphenyl spacer, 4,4′-[4,4′-biphenyldiylbis(sulphonyl-amino)]bis(5-hydroxy-2,7-naphthalenedisulphonic acid) and 3,3′-[4,4′-biphenyldiylbis(sulphonyl-amino)]bis(1,5-naphthalenedisulphonic acid), have previously been reported as potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in cell culture. These compounds have also proved inhibitory to syncytium formation in cocultures of MOLT-4 cells with HIV-1-infected HUT-78 cells. They also inhibit the binding of HIV-1 virions to MT-4 cells as determined by a flow cytometric (FACS) method. Further studies on their mechanism of action by the FACS have revealed that the compounds inhibit the binding of anti-gp120 monoclonal antibody to the viral envelope glycoprotein gp120. Binding of OKT4A/Leu3a monoclonal antibody to the cellular CD4 receptor is not affected by the compounds. These results suggest that the anti-HIV-1 activity of the naphthalenedisulphonic acid derivatives can be attributed to inhibition of the gp120-CD4 interaction through binding of the compounds to the viral gp120 antigen.