Discovery of a novel series of inhibitors of human cytomegalovirus primase

Cushing, Timothy D.; Adrian, Joanna E.; Chen, X.; DiMaio, H.; Doughan, Brandon; Flygare, John A.; Liang, Lingming; Mayorga, V.; Miao, Shichang; Mellon, H.; Peterson, MG; Powers, Jay P.; Spector, F.; Stein, C. A.; Wright, Matthew; Xu, D.; Ye, Q.; Jaén, Juan C.

doi:10.1016/j.bmcl.2006.06.066

Cited by 6 publications

(2 citation statements)

References 16 publications

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“…They outlined that there are some limits to developing helicase inhibitors, due to the fact that (i) the mechanism of action of helicases has not yet been elucidated completely; (ii) helicases share conserved domains with a number of cellular proteins and therefore many helicase-targeted inhibitors could be cytotoxic and (iii) there is a lack of easy and feasible assays to measure inhibition of helicase activity, even though a HTS aimed at identifying HCMV helicase-primase inhibitors has been recently reported [113]. In addition, the crystal structure of neither HSV-1 nor HCMV helicase-primase complexes have yet been resolved, thus impairing the rational design of specific inhibitors.…”

Section: Helicase-primase Complex Inhibitors: the Imidazolyl-pyrimidimentioning

confidence: 98%

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Human cytomegalovirus DNA replication: antiviral targets and drugs

Mercorelli

Sinigalia

Loregian

et al. 2007

Reviews in Medical Virology

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Human cytomegalovirus (HCMV) infection is associated with severe morbidity and mortality in immunocompromised individuals, in particular transplant recipients and AIDS patients, and is the most frequent congenital viral infection in humans. There are currently five drugs approved for HCMV treatment: ganciclovir and its prodrug valganciclovir, foscarnet, cidofovir and fomivirsen. These drugs have provided a major advance in HCMV disease management, but they suffer from poor bioavailability, significant toxicity and limited effectiveness, mainly due to the development of drug resistance. Fortunately, there are several novel and potentially very effective new compounds which are under pre-clinical and clinical evaluation and may address these limitations. This review focuses on HCMV proteins that are directly or indirectly involved in viral DNA replication and represent already established or potential novel antiviral targets, and describes both currently available drugs and new compounds against such protein targets.

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Section: Helicase-primase Complex Inhibitors: the Imidazolyl-pyrimidimentioning

confidence: 98%

“…To date, only a few inhibitors of HCMV UL70 primase have been reported [113][114][115]. A compound that belongs to the imidazolyl-pyrimidine chemical class ( Figure 6) was recently discovered during a HTS which employed a cell-based HCMV-luciferase replication assay.…”

Section: Helicase-primase Complex Inhibitors: the Imidazolyl-pyrimidimentioning

confidence: 99%