Antiherpetic activities of N-alpha-acetyl-nona-D-arginine amide acetate

N-alpha-acetyl-nona-D-arginine amide acetate (ALX40-4C) was developed as a competitive inhibitor of the binding of the HIV Tat protein to its RNA target TAR, which is an intracellular interaction dependent on a short, arginine-rich sequence in Tat. ALX40-4C is a simple mimic of that domain, which is stabilised against enzymatic degradation through inclusion of D-amino acids and terminal protection. The drug inhibits HIV-1 in vitro and is currently being assessed in vivo. In the work reported here, potential activities of the compound against other viruses were examined. As expected, there was little or no activity against most viruses examined, except against some herpesviruses: HSV-1, HSV-2 and CMV. Maximal inhibition of HSV-1 in a plaque reduction assay required pre-incubation with the drug. Maximal inhibition of HCMV, which replicates more slowly than HSV-1, requires exposure to the compound within the first few hours of infection. It appears that the drug inhibits an early step in HSV and HCMV infection. Such a mechanism is consistent with that of other cationic, herpesvirus inhibitors.