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La entrada viral representa una etapa precoz y específica de la infección en la que distintas dianas virales y celulares son accesibles a la intervención terapéutica. En este proceso, CXCR4 y CCR5 actúan como moléculas correceptoras del VIH para su entrada en la célula huésped. El papel preponderante que desempeña el correceptor CCR5 en la transmisión y la propagación del VIH hace de esta molécula la diana de elección para el bloqueo de este mecanismo. En los últimos años se han generado distintos inhibidores específicos de los correceptores del VIH de los que sólo uno, maraviroc, ha sido aprobado para su uso clínico. Los inhibidores sintéticos desarrollados actúan como antagonistas alostéricos que inducen un estado o conformación del correceptor no permisiva para la unión de las glucoproteínas de la envuelta viral. Los antagonistas de CCR5 actúan en un amplio espectro de virus con afinidad o tropismo por este receptor (virus R5), se absorben por vía oral y tienen una potente actividad antiviral. Sin embargo, la perspectiva optimista que ofrecen estas nuevas moléculas inhibidoras hay que moderarla por la posible y esperada aparición de resistencias virales, por una parte, y la propagacion de especies virales con afinidad o tropismo por el receptor CXCR4 (virus X4), por otra. Esta situación es una realidad constatada en los primeros ensayos clínicos con estos fármacos y plantean de manera aguda y urgente la necesidad de disponer de inhibidores eficaces y no tóxicos de CXCR4 para bloquear esta vía alternativa de replicación y de escape viral.
Palabras clave:
VIH
Correceptores
Entrada viral
Quimioterapia antiviral
Viral entry is an early stage and specific of the infection in which different viral and cellular targets are accessible to therapeutic treatment. CXCR4 and CCR5 act in this process as coreceptor molecules of HIV for its entry into the host cell. The predominant role played by the CCR5 coreceptor in the transmission and spreading of HIV makes this molecule the target of choice for blocking this mechanism. In the last few years, different specific inhibitors of HIV coreceptors have been generated of which only one, Maraviroc, has been approved for clinical use. The synthetic inhibitors developed act as allosteric antagonists that induce a non-permissive state or configuration of the coreceptor for binding viral envelope-glycoproteins. The CCR5 antagonists act on a wide spectrum of viruses with affinity or tropism for this receptor (virus R5), are absorbed orally and have powerful antiviral activity. However, the optimistic perspective offered by these new molecules has to be moderated due to the possible and expected appearance of viral resistances, on the one hand, and the propagation of viral species with affinity or tropism for the CXCR4 receptor (virus X4). This situation is a reality verified in the first clinical trials with these drugs and they acutely and urgently show the need to have effective and non-toxic CXCR4 inhibitors available to block this alternative viral replication and escape route.
Key words:
HIV
Coreceptors
Viral entry
Antiviral chemotherapy
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