Abstract
Human immunodeficiency virus (HIV) capsid plays important roles at multiple stages of viral replication. At the initial stages, controlled uncoating (disassembly) of the capsid ensures efficient reverse transcription of the single-stranded RNA genome, into the double-stranded DNA. Whereas at later stages, a proper assembly of capsid ensures the formation of a mature infectious virus particle. Hence, the inhibition of capsid assembly and/or disassembly has been recognized as a potential therapeutic strategy, and several capsid inhibitors have been reported. Of these, PF-3450074 (PF74) has been extensively studied. Recently reported GS-CA inhibitors (GS-CA1 and GS-6207), have shown a strong potential and appear to contain a PF74 scaffold. The location of resistance mutations and the results of structural studies further suggest that GS-CA compounds and PF74 share the same binding pocket, which is located between capsid monomers. Additionally, phenylalanine derivatives containing the PF74 scaffold show slightly enhanced capsid inhibiting activity. A comparison of capsid structures in complex with host factors and PF74, reveals the presence of common chemical entities at topologically equivalent positions. Here we present the status of capsid inhibitors that contain PF74 scaffolds and propose that the PF74 scaffold may be used to develop strong and safe capsid inhibitors.
Highlights
IntroductionRecommended antiretroviral therapies (cART) effectively suppress Human immunodeficiency virus (HIV) and maintain
Recommended antiretroviral therapies effectively suppress Human immunodeficiency virus (HIV) and maintainHIV viral load below the detection levels (
Equivalent three ringof structures of PF74, The proposal that interactions of compounds with both capsid monomers involved in binding site formation may enhance potency of PF74-based molecules, was recently studied by synthesizing
Summary
Recommended antiretroviral therapies (cART) effectively suppress HIV and maintain. Equivalent three ringof structures of PF74, The proposal that interactions of compounds with both capsid monomers involved in binding site formation may enhance potency of PF74-based molecules, was recently studied by synthesizing. The proposal that interactions of compounds with both capsid monomers involved in binding site formation may enhance potency of PF74-based molecules, was recently studied by synthesizing phenylalanine derivatives and testing their inhibitory activity [59]. One of these compounds had a selectivity index (SI) (CC50 /EC50 ) of 13.33 compared to the SI of PF74 (SI = 11.85) [59]. A part of G318-Q319 dipeptide of CPSF6 is topologically close to the indole ring of PF74
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
