The novel
nucleoside analog (1S',2R')-9-[[1',2'-bis(hydroxymethyl)cycloprop-1-yl]methyl]
guanine (A-5021) was previously shown to be a potent inhibitor of the replication of herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella zoster virus (VZV), both in vitro and in vivo (J. Med. Chem. 41, 1284-1298; Antimicrob. Agents Chemother. 42, 1666-1670). Here we demonstrate that
A-5021 is also a potent inhibitor of Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6A and HHV-6B), but that the compound lacks activity against HHV-8.
A-5021, in comparison to
acyclovir, was also assessed for protective activity against HSV-1-induced mortality in SCID mice. The compounds were administered at 50 mg/kg per day by
subcutaneous injection for four consecutive days and treatment was initiated at either 2 h, 1 or 2 days post
infection (p.i.). When administered from day 0 to 4 p.i.,
A-5021 conferred complete protection against the
infection (as assessed at 22 days p.i.), whereas
acyclovir delayed virus induced mortality by only 5 days. When treatment was begun on day 1 or 2,
A-5021 still afforded marked protection against the
infection, whereas
acyclovir was virtually devoid of any activity under these conditions. Our data underline that
A-5021 may offer great promise for the treatment of
herpesvirus infections.