HIV-1 protease inhibitors: effects on HIV-2 replication and resistance.
Novel antiretroviral drugs include protease (PR) inhibitors (e.g. atazanavir, tipranavir and darunavir) that block HIV-1 maturation and show remarkable antiviral potency on drug-resistant isolates. However, the strains used as prototypes in the design of the novel drugs belong to a specific clade (i.e. HIV-1 group M subtype B), which is the most prevalent in developed countries. At the same time, there is an increasing concern about the expansion of other HIV-1 clades as well as other related retroviruses, such as HIV-2. The HIV-2 PR is weakly inhibited by some PR inhibitors (e.g. amprenavir), and little is known of the mutational pathways leading to drug resistance in this virus. The design of specific PR inhibitors targeting HIV-2, or potent drugs showing broad specificity on HIV-1 and HIV-2 clades, remains a major challenge for the future.
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. lmenendez@cbm.uam.es <lmenendez@cbm.uam.es>
Luis
L
Menéndez-Arias
József
J
Tözsér
D001665:Binding Sites; D016503:Drug Delivery Systems; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D011110:Polymorphism, Genetic; D014779:Virus Replication / Q000187:drug effects
D017320:HIV Protease Inhibitors