Current highly active antiretroviral therapy (HAART) provides long term effective virus suppression in patients infected with HIV. However, no definite cure exists and new therapies are essential to effectively control AIDS pandemic. In recent years, HIV capsid protein (CA) has gained increasing momentum as a novel antiviral drug target. HIV capsid exhibits high genetic fragility associated with preserved binding sites for potential ligands. CA targeted small molecules can potentially disrupt multiple steps in viral life cycle including capsid assembly, uncoating and nuclear import. This work will discuss structural and energetic aspects of critical species formation during virus CA core assembly. In addition, findings from the characterization of CA targeted small molecules and their effect on core stability and nuclear transport will be discussed to provide further understanding of mechanisms for the effective inhibition of viral replication via targeting various essential functions of HIV capsid.

Mechanistic lessons of targeting HIV-1 capsid assembly by small molecules

248th National Meeting (2014)

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