title: Inhibiting the HIV integration process: past, present, and the future.
abstract: HIV integrase (IN) catalyzes the insertion into the genome of the infected human cell of viral DNA produced by the retrotranscription process. The discovery of raltegravir validated the existence of the IN, which is a new target in the field of anti-HIV drug research. The mechanism of catalysis of IN is depicted, and the characteristics of the inhibitors of the catalytic site of this viral enzyme are reported. The role played by the resistance is elucidated, as well as the possibility of bypassing this problem. New approaches to block the integration process are depicted as future perspectives, such as development of allosteric IN inhibitors, dual inhibitors targeting both IN and other enzymes, inhibitors of enzymes that activate IN, activators of IN activity, as well as a gene therapy approach.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur, Fondazione Cenci Bolognetti, "Sapienza" Università di Roma , P.le Aldo Moro 5, I-00185 Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D020134:Catalytic Domain; D024882:Drug Resistance, Viral; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015316:Genetic Therapy; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D015658:HIV Infections / Q000628:therapy / Q000821:virology; D019427:HIV Integrase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D016662:Virus Integration / Q000187:drug effects
chemical_list: D020536:Enzyme Activators; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase
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