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Structural and Molecular Interactions of CCR5 Inhibitors with CCR5*
Structural and molecular interactions of CC-chemokine receptor 5 with three CCR5 inhibitors active against R5 human immunodeficiency virus type 1 (HIV-1) including the potent in vitro and in vivo aplaviroc (AVC) are characterized to help design more potent and more HIV-1-specific C CR5 inhibitors. Expand
Altered HIV-1 Gag Protein Interactions with Cyclophilin A (CypA) on the Acquisition of H219Q and H219P Substitutions in the CypA Binding Loop*
The present data suggested that the effect of CypA on HIV-1 replicative WT ability is bimodal (both high and low CypA content limits HIV- 1 replication), that the conformation of the CypA binding region of Gag is important for viral fitness, and that the function of Cyp a is to maintain the conforming. Expand
CCR5 inhibitors: emergence, success, and challenges
Development of potent and metabolically-stable novel CCR5 inhibitors allowing once-daily dosing regimens is needed and development of CXCR4 inhibitors should greatly improve the treatment options available to patients infected with X4- and/or dual-tropic HIV-1 strains in combination with a C CR5 inhibitor. Expand
Potent Inhibition of HIV-1 Replication by Novel Non-peptidyl Small Molecule Inhibitors of Protease Dimerization*
An intermolecular fluorescence resonance energy transfer-based HIV-1-expression assay is developed employing cyan and yellow fluorescent protein-tagged protease monomers and identified non-peptidyl small molecule inhibitors of protease dimerization. Expand
Involvement of the second extracellular loop and transmembrane residues of CCR5 in inhibitor binding and HIV-1 fusion: insights into the mechanism of allosteric inhibition.
C-C chemokine receptor 5 (CCR5), a member of G-protein-coupled receptors, serves as a coreceptor for human immunodeficiency virus type 1 (HIV-1). In the present study, we examined the interactionsExpand
Development of protease inhibitors and the fight with drug-resistant HIV-1 variants.
A variety of novel anti‐HIV‐1 agents that target different steps in the HIV replication cycle are currently in preclinical trials and will undoubtedly improve the ability to manage HIV‐1 infection when they are duly introduced into clinics. Expand
GRL-02031, a Novel Nonpeptidic Protease Inhibitor (PI) Containing a Stereochemically Defined Fused Cyclopentanyltetrahydrofuran Potent against Multi-PI-Resistant Human Immunodeficiency Virus Type 1
GRL-02031 was highly potent against laboratory HIV-1 strains and primary clinical isolates, including subtypes A, B, C, and E (50% effective concentration [EC50] range, 0.015 to 0.038 μM), with minimal cytotoxicity. Expand
4′‐modified nucleoside analogs: Potent inhibitors active against entecavir‐resistant hepatitis B virus
Insight is provided on the structural and functional associations of HBV‐ and HIV‐1‐RTs and CAdA may offer new therapeutic options for HBV patients, and molecular modeling suggests that a shallowerHBV‐RT hydrophobic pocket at the polymerase active site can better accommodate the slightly shorter 4′‐cyano of C adenosine‐triphosphate (TP), but not the longer 4‐ethynyl of EFdA‐TP. Expand
Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance.
A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone, which may lead to novel inhibitors that can combat drug resistance. Expand