Synergy of bovine lactoferrin with the anti-cytomegalovirus drug cidofovir in vitro.
Human cytomegalovirus (HCMV) causes severe morbidity and mortality in immunocompromised patients. Treatment of HCMV infections with conventional antiviral drugs like ganciclovir and cidofovir has major drawbacks (i.e. serious side effects). Therefore, combination therapies using drugs with different antiviral mechanisms should be envisaged. Potential synergy between lactoferrin (LF), an antibacterial, antimycotic and antiviral protein, and the antiviral drugs acyclovir, ganciclovir, foscarnet and cidofovir was investigated, using an in vitro test system with the recombinant RC256 HCMV strain.


RESULTS
Combination of LF with acyclovir and foscarnet resulted in antagonism. When LF and ganciclovir were combined, neither synergy nor antagonism was observed. Strikingly, the combination of LF with cidofovir resulted in marked synergy. The synergistic effect could be explained by inhibition of two subsequent steps in the viral replication cycle: HCMV penetration into the target cells and intracellular synthesis of HCMV DNA. In conclusion, LF might be a potential candidate for combination therapy with cidofovir.
Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration (GUIDE), University Centre for Pharmacy, Ant Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Barry W A
BW
van der Strate
Froukje M
FM
De Boer
Hester I
HI
Bakker
Dirk K F
DK
Meijer
Grietje
G
Molema
Martin C
MC
Harmsen
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004357:Drug Synergism; D017245:Foscarnet / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007781:Lactoferrin / Q000494:pharmacology*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D017245:Foscarnet; D003596:Cytosine; D007781:Lactoferrin; D000077404:Cidofovir; D015774:Ganciclovir; D000212:Acyclovir