Table 1. Genotypic and phenotypic changes selected by serial passage of wild-type virus with GSK3532795.
Selection | Substitutions, % | EC50, μM (FC) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Virus* | P # | Days | Final Conc. (nM) | MA | CA | CA/SP1 | Pr | GSK 3532795 | NFV | ||||||
A | A | V | V | G | R | T | V | A | R | ||||||
118 | 119 | 159 | 218 | 221 | 286 | 332 | 362 | 364 | 41 | ||||||
T | V | I | M | E | K | S | I | V | G | ||||||
WT | 0 | - | 0 | - | - | - | - | - | - | - | - | - | - | 0.002 | 0.004 |
8 | 63 | 0 | - | - | - | 100 | - | - | - | - | - | - | 0.001 (<1) | 0.002 (<1) | |
8 | 97 | 256 | 60 | - | - | 100 | - | - | 100 | 100 | - | 100 | 0.257 (128) | 0.001 (<1) | |
8 | 83 | 256 | - | - | - | - | 100 | - | - | - | 100 | - | 2.3 (>1000) | 0.002 (<1) | |
WT p12 | 0 | - | 0 | - | - | - | - | - | - | - | - | - | - | nd | nd |
8 | 63 | 0 | - | 20 | - | 100 | - | - | - | - | - | - | 0.001 (<1) | 0.002 (<1) | |
8 | 70 | 256 | - | - | - | 100 | - | - | - | 10 | 100 | - | 0.43 (21) | 0.001 (<1) | |
8 | 70 | 256 | - | - | 20 | 100 | - | 40 | - | 20 | 90 | - | 0.88 (44) | 0.002 (<1) |
CA, capsid; EC50, 50% effective concentration; FC, fold change relative to starting virus; MA, matrix; nd, not done; NFV, nelfinavir; P#, passage number; Pr, protease; SP1, spacer peptide 1; WT, wild-type
*NL4-3 Gag P373S reporter-free virus, without (WT) or with (WTp12) prior culture adaptation