A new acyclic heterodinucleotide active against human immunodeficiency virus and herpes simplex virus |
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Authors: | Franchetti P Abu Sheikha G Cappellacci L Marchetti S Grifantini M Balestra E Perno C Benatti U Brandi G Rossi L Magnani M |
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Institution: | Dipartimento di Scienze Chimiche, Università di Camerino, 62032, Camerino, Italy. frapa@camserv.unicam.it |
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Abstract: | The most common therapies against human herpes virus (HSV-1) and human immunodeficiency virus (HIV-1) infectivity are based on the administration of nucleoside analogues. Acyclovir (ACV) is the drug of choice against HSV-1 infection, while the acyclic nucleoside phosphonate analogue PMPA has shown marked anti-HIV activity in a phase I and II clinical studies. As monocyte-derived macrophages are assumed to be important as reservoirs of both HSV-1 and HIV-1 infection, new approaches able to inhibit replication of both viruses in macrophages should be welcome. ACVpPMPA, a new heterodinucleotide consisting of both an antiherpetic and an antiretroviral drug bound by a phosphate bridge, was synthesized and encapsulated into autologous erythrocytes modified to increase their phagocytosis by human macrophages. ACVpPMPA-loaded erythrocytes provided an effective in vitro protection against both HSV-1 and HIV-1 replication in human macrophages. |
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