Title: Selective inhibition of human cytomegalovirus DNA synthesis by (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG)
Authors: Neyts, Johan ×
Snoeck, Robert
Schols, Dominique
Balzarini, Jan
De Clercq, Erik #
Issue Date: Nov-1990
Series Title: Virology vol:179 issue:1 pages:41-50
Abstract: The novel acyclic nucleoside phosphonate, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC], is a potent and selective inhibitor of human cytomegalovirus (CMV) replication in cell culture. (S)-HPMPC inhibits CMV DNA synthesis in a concentration-dependent manner within the concentration range of 0.04-4 micrograms/ml. At 4 micrograms/ml, viral DNA synthesis is completely suppressed. (S)-HPMPC proved more inhibitory to CMV replication and CMV DNA synthesis than 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir), the current drug of choice for the treatment of CMV infections. Both compounds affected cell proliferation and cellular DNA synthesis only at a concentration that was 100- to 500-fold higher than the antivirally effective concentrations. In accord with the postulated target (viral DNA synthesis) for its antiviral action, (S)-HPMPC did not prevent immediate early antigen expression in CMV-infected cells. A limited exposure time (as short as 6 hr postinfection) of the CMV-infected cells to (S)-HPMPC sufficed to afford a pronounced and prolonged inhibition of viral DNA synthesis and virus replication. This gives (S)-HPMPC a definite advantage over DHPG, which only afforded a weak and transient inhibition of CMV DNA synthesis and virus replication after it had been exposed to the cells for a short exposure time. The long-lasting antiviral action of (S)-HPMPC is a unique property that opens new therapeutic modalities for the treatment of virus infections.
ISSN: 0042-6822
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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