Abstract: AIDS is one of the most devastating pandemic. All drugs designed have targeted the viral protein the GP120. The entry of Human Immuno Virus (HIV) into the human cells is initiated by a temporary interaction between the viral exterior glycoprotein GP120 and human CD4 receptor. The primary receptor CD4 glycoprotein present on the cell surface of T-helper cells interacts with GP120. The GP120-CD4 complex involves the D1-D2 domain of the human CD4 and conserved regions of the viral protein GP120. The interaction leads to a number of conformational changes in the inner domains and bridging sheets of glycoprotein GP120 due to translocations and deletions, which creates a binding site in the V3 loop of GP120 for chemokine receptors (CCR5/CXCR4) present on the cell surface.