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Figure 1: Stampidine Inhibits NRTI-Resistant HIV with Subnanomolar/ Nanomolar Potency.
A: Dendrograms were drawn to illustrate similar Fold Resistance profiles from joining pairs of closely related median Fold Resistance values profiles, whereby drug and HIV isolates joined by short branch lengths showed most similarity. Mutation combination for each of the HIV-1 isolates/clones was cross-referenced with drug susceptibility results of sequences matching input query for known NRTi Drug Resistrance Mutations on the Stanford University HIV Drug Resistance Database. Fold resistance values were compiled for all HIV-1 isolates/ clones against 7 nucleoside/nucleotide analog drugs (Abacavir (ABC); Didanosine (DDI); Zalcitabine (DDC); Lamivudine (3TC); Stavudine (D4T); Tenofovir (TDF); Zidovudine (ZDV)), and the median value was depicted using a heat map for each isolate (rows) and each drug (column) following a 2-way agglomerative hierarchical clustering technique to organize expression patterns using the Average distance linkage method such that HIV isolates (rows) having similar Fold Resistance values across drug profiles and across HIV isolates were grouped together. Dendrograms were drawn to illustrate similar Fold Resistance profiles from joining pairs of closely related median Fold Resistance values profiles, whereby drug and HIV isolates joined by short branch lengths showed most similarity. Stampidine exhibited potent anti-HIV activity against each isolate with subnanomolarlow nanomolar IC50 values.
B: Anti-HIV potency of Stampidine for each of the HIV-1 isolates (virus isolates are ordered vertically as shown in panel A) is illustrated using a bar chart of the IC50 values (log scale).
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