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S/GSK1349572, also known as dolutegravir, is a novel and potent inhibitor of human immunodeficiency virus (HIV) integrase (IN) blocking the strand transfer of integration of the viral genome into the host cell’s DNA. It occupies the physical space in the IN active site of the intasome, contacts with the β4-α2 loop of the catalytic core domain, and enters into the pocket vacated by the displaced viral DNA through its extended linker region connecting the metal chelating core the halobenzyl group.  S/GSK1349572 exhibits potent anti-HIV activity in peripheral blood mononuclear cells (IC50 = 0.51 nM) in vitro and retains activity against raltegravir- and elvitegravir- resistant HIV.

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