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PMID: 6302704 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 80 ·No. 9 ·1983-05-00 ·Pages 2767-70

Cheng YC, Huang ES, Lin JC, Mar EC, Pagano JS, Dutschman GE, Grill SP

Abstract

A guanosine analog, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG), was found to inhibit herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, cytomegalovirus, and Epstein-Barr virus replication by greater than 50% at concentrations that do not inhibit cell growth in culture. The potency of the drug against all of these viruses is greater than that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir). DHPG was active against HSV-1 growth during the early phase of virus replication and had no activity when added at a later time after infection. Its antiviral activity was irreversible. Thymidine partially neutralized its action. The anti-HSV-1 activity of DHPG was dependent on the induction and the properties of virus-induced thymidine kinase. Virus variants that induced altered virus thymidine kinase and became resistant to acyclovir were still as sensitive to DHPG as the parental virus. DHPG is active against five different HSV variants with induced altered DNA polymerase and resistance to acyclovir.

MeSH Terms
Acyclovir/analogs & derivatives,pharmacology Animals Cytomegalovirus/drug effects,physiology DNA-Directed DNA Polymerase/metabolism Ganciclovir Herpesviridae/drug effects,physiology Herpesvirus 4, Human/drug effects,physiology Humans Infant, Newborn Male Simplexvirus/drug effects Thymidine Kinase/metabolism Virus Replication/drug effects
Chemicals
Thymidine Kinase DNA-Directed DNA Polymerase Ganciclovir Acyclovir
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cheng Y C
Huang E S
Lin J C
Mar E C
Pagano J S
Dutschman G E
Grill S P
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22 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.80.9.2767
Published
1983-05-00
Pages
2767-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC393909
Subset
IM
Grants
NIAID NIH HHS · AI-12717 · United States
NCI NIH HHS · CA-19014 · United States
NCI NIH HHS · CA21773 · United States
External Links
PubMed source DOI: 10.1073/pnas.80.9.2767 PMC Full Text View journal details
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