TIN PROTOPORPHYRIN-IX USED IN CONTROL OF HEME METABOLISM IN HUMANS EFFECTIVELY INHIBITS HIV-1 INFECTION

Recent observations indicated that several porphyrins bound to the V3 loop of the envelope glycoprotein gp 120 of the human immunodeficiency virus type 1 (HIV-1) and inhibited infection of cells by HIV-1. The t in derivative of protoporphyrin IX (Sn-PTP-IX) has already been used c linically in humans to suppress hyperbilirubinemia. It was therefore o f interest to determine whether Sn-PTP-IX has anti-HIV-l activity. It is demonstrated here that Sn-PTP-IX effectively inhibited infection by several HIV-1 isolates (IIIB, MN, RF, SF-2 and two isolates resistant to azidothymidine). This was surprising, since earlier studies indica ted that incorporation of other metals into porphyrins markedly decrea sed their antiviral activity. Sn-PTP-IX blocked the binding to gp 120 of anti-V3-loop-specific antibodies and of monoclonal antibodies speci fic for the CD4 binding site on gp 120. The latter effect appeared to be allosteric and was not observed with a deletion mutant of gp 120 la cking the V3 loop sequence. This suggests that Sn-PTP-IX binds to the V3 loop and distorts the native conformation of the HIV-1 envelope, th ereby preventing infection. These results merit the consideration of S n-PTP-IX as a prophylactic and chemotherapeutic agent against HIV-1.