A new acyclic heterodinucleotide active against human immunodeficiency virus and herpes simplex virus.
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.
Franchetti
P
P
Dipartimento di Scienze Chimiche, Università di Camerino, 62032, Camerino, Italy. frapa@camserv.unicam.it
Abu Sheikha
G
G
Cappellacci
L
L
Marchetti
S
S
Grifantini
M
M
Balestra
E
E
Perno
C
C
Benatti
U
U
Brandi
G
G
Rossi
L
L
Magnani
M
M
D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004337:Drug Carriers; D004912:Erythrocytes / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D009705:Nucleosides / Q000378:metabolism / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
C120723:ACVpPMPA; D019380:Anti-HIV Agents; D004337:Drug Carriers; D009705:Nucleosides; D011355:Prodrugs