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Antimicrobial Agents and Chemotherapy, July 1998, p. 1666-1670, Vol. 42, No. 7
0066-4804/98/$00.00+0

Antiherpesvirus Activities of (1'S,2'R)-9-{[1',2'-Bis(hydroxymethyl)cycloprop-1'-yl]methyl}guanine (A-5021) in Cell Culture

Satoshi Iwayama,1,* Nobukazu Ono,1 Yuko Ohmura,1 Katsuya Suzuki,1 Miho Aoki,1 Harumi Nakazawa,1 Miki Oikawa,1 Tamamo Kato,1 Masahiko Okunishi,1 Yukihiro Nishiyama,2 and Koichi Yamanishi3

Life Science Laboratories, Ajinomoto Co., Inc., Totsuka-ku, Yokohama 244,1 Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Showa-ku, Nagoya 466,2 and Department of Microbiology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565,3 Japan

Received 16 December 1997/Returned for modification 6 February 1998/Accepted 5 May 1998

Antiherpetic activity of (1'S,2'R)-9-{[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl}guanine (A-5021) was compared with those of acyclovir (ACV) and penciclovir (PCV) in cell cultures. In a plaque reduction assay using a selection of human cells, A-5021 showed the most potent activity in all cells. Against clinical isolates of herpes simplex virus type 1 (HSV-1, n = 5) and type 2 (HSV-2, n = 6), mean 50% inhibitory concentrations (IC50s) for A-5021 were 0.013 and 0.15 µg/ml, respectively, in MRC-5 cells. Corresponding IC50s for ACV were 0.22 and 0.30 µg/ml, and those for PCV were 0.84 and 1.5 µg/ml, respectively. Against clinical isolates of varicella-zoster virus (VZV, n = 5), mean IC50s for A-5021, ACV, and PCV were 0.77, 5.2, and 14 µg/ml, respectively, in human embryonic lung (HEL) cells. A-5021 showed considerably more prolonged antiviral activity than ACV when infected cells were treated for a short time. The selectivity index, the ratio of 50% cytotoxic concentration to IC50, of A-5021 was superior to those of ACV and PCV for HSV-1 and almost comparable for HSV-2 and VZV. In a growth inhibition assay of murine granulocyte-macrophage progenitor cells, A-5021 showed the least inhibitory effect of the three compounds. These results show that A-5021 is a potent and selective antiviral agent against HSV-1, HSV-2, and VZV.

* Corresponding author. Mailing address: Life Science Laboratories, Ajinomoto Co., Inc., 214 Maeda-cho, Totsuka-ku, Yokahama 244, Japan. Phone: 81-45-821-7405. Fax: 81-45-822-5211. E-mail: ll_iwayama{at}te3.ajinomoto.co.jp.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1666-1670, Vol. 42, No. 7
0066-4804/98/$00.00+0


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