We superimposed the X - ray structure of 23 - bound HIV-1 protease ( wild - type ) with the three most highly mutated drugresistant proteases . [ 51 ] These structures showed minimal rootmean - square deviation of the a - carbon backbone atoms ( 0.5 to 1.1 ) suggesting inhibitor 23 should retain good to excellent contacts with the backbone of the mutant proteases . As it turned out , inhibitor 23 exerted very potent activity against HIV-1 isolates ( HIV-1 LAI and HIV-1 Ba - L ) in both MT-2 cells and PHA - PBMC ( Table 10 ) . Furthermore , as evident in Table 9 , inhibitor 23 retained significant antiviral activity against a panel of HIV-1 drug - resistant viral strains . Inhibitor 23 displayed the most potent activity ( IC 50 = 3 nm ) against HIV-1 clinical strain HIV-1 ET , which had been isolated from a drug - naive patient . Furthermore , six drug - resistant clinical strains containing 10 - 12 amino acid substitutions associated with protease inhibitor resistance ( HIV-1 B , HIV-1 C , HIV-1 G , HIV-1 TM , HIV-1 EV , and HIV-1 ES ) were isolated from patients with HIV-1 infection having received 7 - 11 different antiviral agents for 24 to 81 months . [ 82,105 ] All tested approved PIs were highly resistant . However , inhibitor 23 exerted highly potent activity against all of these six variants with IC 50 values ranging from 4 nm to 52 nm . Inhibitor 23 was also highly potent against HIV-1 K with an IC 50 value as low as 3 nm . This data indicate that inhibitor 23 is highly active against a wide spectrum of drug - resistant variants . [ 51 ] 6.2 . Design of meso - Hexahydrocyclopenta-1,3 - dioxolane as a P2 Ligand