Figure 4.

Discovery of dapivirine from the alpha-anilinophenylacetamide ($\alpha$-APA) derivatives to imidoyl thiourea derivatives, the diaryltriazine derivatives, and the diarylpyrimidine derivatives. Drug binding pocket of dapivirine is highlighted in HIV-1 reverse transcriptase (PDB code: 1S6Q). Amino acid positions with drug resistant residues are highlighted. Three amino acid substitutions (L100I, K103N, A98G) may cause resistance to dapivirine^74,78.