L-thymidine is phosphorylated by herpes simplex virus type 1 thymidine kinase and inhibits viral growth

Article abstract of DOI:10.1021/jm00100a029

We have demonstrated that herpes simplex 1 (HSV1) thymidine kinase (TK) shows no stereospecificity for D- and L-β-nucleosides. In vitro, L enantiomers are not recognized by human TK, but function as specific substrates for the viral enzyme in the order: L-thymidine (L-T) >> 2'-deoxy- L-guanosine (L-dG) > 2'-deoxy-L-uridine (L-dU) > 2'-deoxy-L-cytidine (L-dC) > 2'-deoxy-L-adenosine (L-dA). HSV1 TK phosphorylates both thymidine enantiomers to their corresponding monophosphates with identical efficiency and the K(i) of L-T (2 μM) is almost identical to the K(m) for the natural substrate D-T (2.8 μM). The L enantiomer reduces the incorporation of exogenous [³H]T into cellular DNA in HeLa TK-/HSV1 TK⁺ but not in wild-type HeLa cells, without affecting RNA, protein synthesis, cell growth, and viability. L-T markedly reduces HSV1 multiplication in HeLa cells. Our observations could lead to the development of a novel class of antiviral drugs characterized by low toxicity.