A data mining study has been done using HIV-1 protease crystal structures complexed with FDA approved HIV-1 protease inhibitor drugs. Chemical descriptors have been computed for the binding pockets of each crystal structure, yielding approximately 600 constitutional, topological, geometric, elecrotostatic, and quantum mechanical descriptors for each structure. Several supervised (hybrid binary ...

Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has also been described in some viruses from antiretroviral agent-naive patients with primary HIV-1 infection in association with combinations of amino acid change...

Despite the effectiveness of currently available human immunodeficiency virus type 1 (HIV-1) therapies, a continuing need exists for new drugs to treat HIV-1 infection. We investigated the mechanism by which 3-O-[3',3'-dimethylsuccinyl]-betulinic acid (DSB) inhibits HIV-1 replication. DSB functions at a late stage of the virus life cycle but does not inhibit the HIV-1 protease in vitro or inter...

For the AIDS virus to mature, HIV protease must process the viral polyproteins gag and gag-pol specifically at nine non-homologous sites [1]. The protease has been a prime target in the massive structure-based drug design effort to combat AIDS, since it is essential to viral maturation. The inhibition of HIVs protease has been reaching success on clinical treatments. However, the fast emergency...

Pharmacoinformatics approaches are widely used in the field of drug discovery as it saves time, investment and animal sacrifice. In the present study, pharmacore-based virtual screening was adopted to identify potential HIV-protease ligands as anti-HIV agents. Pharmacophore is the 3D orientation and spatial arrangement of functional groups that are critical for binding at the active site cavity...

The development of antiretroviral (ARV) drugs and their use in human immunodeficiency virus type 1 (HIV-1) has led to the effective control of HIV replication in infected patients. However the emergence of resistant HIV-1 strains still remains a problem. Literature has shown that mutations may accumulate in the protease (PR) and gag regions of HIV-1 patients who fail therapy with protease inhib...

HIV-1 aspartyl protease (PR) plays a key role in virion morphogenesis, underscoring the effectiveness of protease inhibitors (PI). Despite their utility, side effects and drug-resistance remains a problem. We report the development of RNA aptamers as inhibitors of HIV-1 PR for potential use in anti-HIV gene therapy. Employing Systematic Evolution of Ligands by Exponential Enrichment (SELEX), we...

By using a structure-based computer-assisted search, we have found a butyrophenone derivative that is a selective inhibitor of the human immunodeficiency virus 1 (HIV-1) protease. The computer program creates a negative image of the active site cavity using the crystal structure of the HIV-1 protease. This image was compared for steric complementarity with 10,000 molecules of the Cambridge Crys...

Inhibition of HIV-1 protease (HIV-PR), the aspartic protease that cleaves specific amide bonds in precursor gag-pol proteins to form the mature proteins needed for production of infectious human immunodeficiency virus (HIV) particles,' is regarded as a promising approach for treating acquired immunodeficiency syndrome (AIDS) and related diseases. Tight-binding inhibitors of HIV-PR have been dis...

The HIV Reverse Transcriptase and Protease Sequence Database is an on-line relational database that catalogs evolutionary and drug-related sequence variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease enzymes, the molecular targets of anti-HIV therapy (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protea...