Rilpivirine analogs potently inhibit drug-resistant HIV-1 mutants

Molecular mechanics analysis of drug-resistant mutants of HIV protease.

Drug-resistant mutants of HIV-1 protease limit the long-term effectiveness of current anti-viral therapy. In order to study drug resistance, the wild-type HIV-1 protease and the mutants R8Q, V32I, M46I, V82A, V82I, V82F, I84V, V32I/I84V and M46I/I84V were modeled with the inhibitors saquinavir and indinavir using the program AMMP. A new screen term was introduced to reproduce more correctly the...

Knowledge-Based Avoidance of Drug-Resistant HIV Mutants

scientific AIDS literature describing specific human immunodeficiency virus (HIV) drug resistances directly to the customized treatment strategy of a specific HIV patient. Rules in the CTSHIV knowledge base encode knowledge about sequence mutations in the HIV genome that have been found to result in drug resistance to the HIV virus. Rules are applied to the actual HIV sequences of the virus str...

Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants

Convenient drug-resistance testing of viral mutants is indispensable to effective treatment of viral infection. We developed a novel fluorometric assay for phenotypic differentiation of drug-resistant mutants of human immunodeficiency virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR ...

Crystal structures of wild-type and drug-resistant mutants of HIV-1 protease complexed to Ritonavir

Artificial peptides conjugated with cholesterol and pocket-specific small molecules potently inhibit infection by laboratory-adapted and primary HIV-1 isolates and enfuvirtide-resistant HIV-1 strains.

OBJECTIVES To develop new HIV-1 fusion inhibitors with improved antiviral activities and resistance profiles, we designed two categories of artificial peptides, each containing four heptad repeats (m4HR) conjugated with a pocket-specific small molecule (pssm) or pssm and cholesterol (chol), designated pssm-m4HR or pssm-m4HR-chol, respectively, and tested their anti-HIV-1 activity. METHODS We ...