CDK9 inhibitor FIT-039 prevents replication of multiple DNA viruses.

A wide range of antiviral drugs is currently available; however,
drug-resistant viruses have begun to emerge and represent a potential
public health risk. Here, we explored the use of compounds that inhibit
or interfere with the action of essential host factors to prevent virus
replication. In particular, we focused on the cyclin-dependent kinase 9
(CDK9) inhibitor, FIT-039, which suppressed replication of a broad
spectrum of DNA viruses through inhibition of mRNA transcription.
Specifically, FIT-039 inhibited replication of herpes simplex virus 1
(HSV-1), HSV-2, human adenovirus, and human cytomegalovirus in cultured
cells, and topical application of FIT-039 ointment suppressed skin
legion formation in a murine HSV-1 infection model. FIT-039 did not
affect cell cycle progression or cellular proliferation in host cells.
Compared with the general CDK inhibitor flavopiridol, transcriptome
analyses of FIT-039-treated cells revealed that FIT-039 specifically
inhibited CDK9. Given at concentrations above the inhibitory
concentration, FIT-039 did not have a cytotoxic effect on mammalian
cells. Importantly, administration of FIT-039 ameliorated the severity
of skin lesion formation in mice infected with an acyclovir-resistant
HSV-1, without noticeable adverse effects. Together, these data indicate
that FIT-039 has potential as an antiviral agent for clinical
therapeutics.