Inhibitors of protein-processivity factor

Harvard investigators have discovered that Pol interacts with a processivity factor at a site that is distinct from sites of normal interaction between known Pol family members and other cellular factors. Unlike most protein-protein interactions, the target site is uniquely suited to small molecule drug discovery. Structure-based methods of designing and screening candidate drugs aimed at disrupting Pol processivity factor binding at this target site are fully disclosed.

Applications

Herpes virus infection underlies a broad range of pathological conditions requiring long-term treatment in affected individuals. Genital herpes and sight-threatening ocular infections result from the infection of immunocompetent adults with herpes simplex virus (HSV), while human cytomegalovirus (CMV) produces diseases in immunosuppressed adults and transplant patients and is a major cause of birth defects. 'Productive' infection relies upon efficient replication of the viral genome in the affected host. Herpes virus DNA replication is enhanced by the interaction of virally-encoded processivity factors with host cell polymerase (Pol) molecules.

The disclosed invention is applicable to the design of a broad class of antiviral agents. Treatment of viral infection using drugs developed according to these methods is additionally encompassed by the invention.

Intellectual Property Status: Patent(s) Pending