The nonequilibrium mechanism of noise-enhanced drug synergy in HIV latency reactivation.

ABSTRACT: Noise-modulating chemicals can synergize with transcriptional activators in reactivating latent HIV to eliminate latent HIV reservoirs. To understand the underlying biomolecular mechanism, we investigate a previous two-gene-state model and identify two necessary conditions for the synergy: an assumption of the inhibition effect of transcription activators on noise enhancers; and frequent transitions to the gene non-transcription-permissive state. We then develop a loop-four-gene-state model with Tat transcription/translation and find that drug synergy is mainly determined by the magnitude and direction of energy input into the genetic regulatory kinetics of the HIV promoter. The inhibition effect of transcription activators is actually a phenomenon of energy dissipation in the nonequilibri

SUBMITTER: Guo X 

PROVIDER: S-EPMC9127169 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature