RO0504985 is an inhibitor of CMGC kinase proteins and has anti-human cytomegalovirus activity


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Abstract

Public-private partnerships allow many previously unavailable compounds to be screened for antiviral activity. Here a screening method was used to identify an oxindole compound, RO0504985, from a Roche kinase inhibitor library that inhibited human cytomegalovirus (HCMV) protein production. RO0504985 was previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2). However, using kinase selectivity assays it was found that RO0504985 was an inhibitor of several CMGC group kinase proteins, including CDK2. Using virus yield reduction assays it was observed that RO0504985 inhibited replication of different HCMV strains at low micromolar concentrations. Western blotting was used to investigate how RO0504985 inhibited HCMV replication. Treatment of HCMV infected cells with RO0504985 inhibited production of the immediate early viral IE2 proteins and the late viral protein pp28. Thus, RO0504985 inhibited HCMV replication by preventing production of specific HCMV proteins necessary for virus replication.HighlightsScreening of kinase inhibitors in HCMV infected cells was conducted via a public-private partnership.An oxindole compound, RO0504985, was found to have anti-HCMV activity.RO0504985 was discovered to be an inhibitor of a range of CMGC protein kinases.RO0504985 inhibited HCMV replication by preventing production of viral immediate-early and late proteins.

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