Drug target site within GP120 of HIV

A method of generating a medicament for the treatment of HIV, comprising confirming that a known compound is an inhibitor of the binding of HIV (human immunodeficiency virus) glycoprotein (gp)120 to a CD4-receptor comprising the method of

• (a) bringing into contact a HIV gp120 or a peptidomimetic reflecting the three-dimensional structure of said gp120 and the known compound;
• (b) determining whether said known compound interacts with at least two amino acid residues found independently in each of three of six motifs, said three of six motifs selected from the group consisting of motif 1, motif 2 and motif 3, within the 3-dimensional structure of said gp120 or within a peptidomimetic reflecting the 3-dimensional structure of said gp120,
• wherein a first motif of said six motifs comprises the amino acid sequence DIISLWDQSLKPCVKLT (SEQ ID NOS 3 (HIV-1) or 9 (HIV-2);
• motif 1);
• wherein a second motif of said six motifs comprises the amino acid sequence NVSTVQCTHGIRPVVSTQLLLNGSLAE (SEQ ID NOS 4 (HIV-1) or 10 (HIV-2);
• motif 2) and wherein the interaction with any amino acid residue of said second motif is with any one or more of residues 14-18 of SEQ ID NOS 4 (HIV-1) or 10 (HIV-2);
• wherein a third motif of said six motifs comprises the amino acid sequence SGGDPEIVMHSFNCGGEFFYCN (SEQ ID NOS 5 (HIV-1) or 11 (HIV-2);
• motif 3);
• wherein a fourth motif of said six motifs comprises the amino acid sequence CPKISFEP (SEQ ID NOS 6 (HIV-1) or 14 (HIV-2));
• wherein a fifth motif of said six motifs comprises the amino acid sequence FRPGGGDMRDNWRSELYKYKVV (SEQ ID NO:
• 7 (HIV-1));
• and
• wherein a sixth motif of said six motifs comprises the amino acid sequence CSS, said gp120 of HIV comprising or consisting of:
• (i) the sequence of SEQ ID NO:
• 2;
• (ii) the sequence encoded by the sequence of SEQ ID NO:
• 1;
• (iii) a sequence being at least 50% identical to the sequence of SEQ ID NO:
• 2 or to the sequence encoded by the sequence of SEQ ID NO:
• 1;
• or
• (iv) a sequence encoded by a sequence being at least 50% identical to the sequence of SEQ ID NO:
• 1, and
• (c) identifying as inhibitors those known compounds which interact with at least two amino acid residues found independently in each of three of six motifs selected from the group consisting of motif 1, motif 2 and motif 3 in said six motifs within the 3-dimensional structure of said gp120 in (b), followed by screening the inhibitor in a biological assay.