Cell Cycle-Dependent Kinase Cdk9 Is a Postexposure Drug Target against Human Adenoviruses

• DOI: 10.1021/acsinfecdis.7b00009
• Publication Date: 2017-04-24T04:50:04Z
• Authors: Vibhu Prasad; Maarit Suomalainen; Silvio Hemmi; Urs F. Greber
• Keywords: Antiviral drug

Human adenoviruses (HAdVs) infect respiratory, gastrointestinal, and urinary tracts give rise to eye infections epidemic keratoconjunctivitis (EKC). They persist in lymphoid tissue cause morbidity mortality immunocompromised people. Treatments with significant postexposure efficacy are not available. Here, we report that inhibition of the cell cycle-dependent kinase 9 (Cdk9) by RNA interference, or compound flavopiridol, blocked HAdV-C2/5, EKC-causing HAdV-D8/37, progeny formation human corneal epithelial cancer cells. Flavopiridol abrogated production immediate early viral transactivating protein E1A without affecting nuclear import DNA. In morphometric plaque assays, exhibited antiviral both pre- regimens therapeutic indexes exceeding 10. The study identifies Cdk9 as a drug target against adenovirus vitro suggests clinically tested anticancer flavopiridol is candidate for treating adenoviral EKC emergence upon immune suppression.