Growth Inhibition by Acycloguanosine of Herpesviruses Isolated from Human Infections

Author:

Crumpacker Clyde S.1,Schnipper Lowell E.2,Zaia John A.3,Levin Myron J.3

Affiliation:

1. Division of Infectious Disease Department of Medicine and Thorndike Laboratory of Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215

2. Division of Oncology, Department of Medicine and Thorndike Laboratory of Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215

3. Division of Clinical Microbiology, Sidney Farber Cancer Institute, Boston, Massachusetts 02215

Abstract

Inhibition by acycloguanosine (ACG) of plaque formation by harpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus was studied. Seventeen clinical isolates of HSV-1 were inhibited by ACG at a mean 50% inhibitory dose (ID50) of 0.15 ± 0.09 μM. The mean ID50for 10 isolates of HSV-2 was 1.62 ± 0.76 μM, and for four isolates of varicella-zoster virus it was 3.75 ± 1.30 μM. The ID50's for two cytomegalovirus isolates were 100 and 160 μM, and for four additional isolates of cytomegalovirus no end point (ID50) was reached at 200 μM. ACG at a concentration of 200 μM had no effect on deoxyribonucleic acid synthesis in human fibroblast cells and only inhibited thymidine incorporation by Vero cells by one-third. These studies demonstrated the antiviral activity of ACG against clinical isolates of HSV-1, HSV-2, and varicella-zoster virus and the lack of toxicity to monkey or human cells in culture at concentrations which markedly inhibited these viruses. ACG had little effect on cytomegalovirus at concentrations in excess of 100 μM.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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