R00504985 is an inhibitor of CMGC kinase proteins and has anti-human cytomegalovirus activity

摘要

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, R00504985, from a Roche kinase inhibitor library that inhibited human cytomegalovirus (HCMV) protein production. R00504985 was previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2). However, using kinase selectivity assays it was found that R00504985 was an inhibitor of several CMGC group kinase proteins, including CDK2. Using virus yield reduction assays it was observed that R00504985 inhibited replication of different HCMV strains at low micromolar concentrations. Western blotting was used to investigate how R00504985 inhibited HCMV replication. Treatment of HCMV infected cells with R00504985 inhibited production of the immediate early viral 1E2 proteins and the late viral protein pp28. Thus, R00504985 inhibited HCMV replication by preventing production of specific HCMV proteins necessary for virus replication. Crown Copyright (C) 2017 Published by Elsevier B.V. All rights reserved.