Reference

Red blood cells mediated delivery of 9-(2-phosphonylmethoxyethyl)adenine to primary macrophages: efficiency, metabolism and activity against human immunodeficiency virus or herpes simplex virus

Red blood cells mediated delivery of 9-(2-phosphonylmethoxyethyl)adenine to primary macrophages: efficiency, metabolism and activity against human immunodeficiency virus or herpes simplex virus. Perno, Carlo-Federico; Santoro, Nadia; Balestra, Emanuela; Aquaro, Stefano; Cenci, Alessandra; Lazzarino, Giuseppe; Di Pierro, Donato; Tavazzi, Barbara; Balzarini, Jan; Garaci, Enrico; Grimaldi, Settimio; Calio, Raffaele (Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata', Via di Tor Vergata 135, Rome 00133, Italy). Antiviral Research, 33(3), 153-164 (English) 1997 Elsevier. CODEN: ARSRDR. ISSN: 0166-3542. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 63 Red blood cells (RBC) may act as selective carriers of drugs to macrophages, an important reservoir of viruses such as human immunodeficiency virus (HIV) and herpes simplex virus type 1 (HSV-1).Some commonly used reagents like 106941-25-7 and 129532-77-0 are used in this experiment. We therefore assessed the incorporation of 9-(2-phosphonylmethoxyethyl)adenine (PMEA, a potent inhibitor of HIV and HSV-1) into RBC, its delivery to macrophages and its activity against HIV or HSV-1. Loading of PMEA in artificially aged opsonized RBC affords significant levels of intracellular PMEA. RBC metabolize PMEA to its active congener PMEA-diphosphate, although with low efficiency. Exposure of macrophages to RBC-encapsulated PMEA inhibits the replication of both HIV and HSV-1 (about 90% inhibition at the highest RBC:macrophages ratios) even if RBC were removed before virus challenge. By contrast, the antiviral activity of free PMEA removed before virus challenge was irrelevant at concns. up to 150-fold higher than the 50% effective concn. (EC50). Finally, the antiviral effect of RBC-encapsulated PMEA correlates with PMEA levels in macrophages about 500-fold higher than those achieved by free PMEA (at concns. 10-fold higher than the EC50). The efficacy of RBC-mediated delivery to macrophages of PMEA (and perhaps of compds. with shorter intracellular half-lives) warrants further studies in infectious diseases involving phagocytizing cells as main targets of the pathogen. .

Early treatment with 9-(2-phosphonylmethoxyethyl)adenine reduces virus burdens for a prolonged period in SIV-infected rhesus macaques

Early treatment with 9-(2-phosphonylmethoxyethyl)adenine reduces virus burdens for a prolonged period in SIV-infected rhesus macaques.Several substances are used for example 106941-25-7 which is its cas registry number. Joag, Sanjay V.; Li, Zhuang; Foresman, Larry; Pinson, David M.; Stephens, Edward B.; Raghavan, Ravi; Nave, Jean-Francois; Casara, Patrick; Narayan, Opendra (Marion Merrell Dow Laboratory of Viral Pathogenesis and Department of Microbiology, University of Kansas Medical Center, Kansas City, KS 66160, USA). AIDS Research and Human Retroviruses, 13(3), 241-246 (English) 1997 Liebert. CODEN: ARHRE7. ISSN: 0889-2229. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) We evaluated the effects of a reverse transcriptase inhibitor, 9-(2-phosphonylmethoxyethyl)adenine (PMEA), on simian immunodeficiency virus (SIV) infection in rhesus macaques (Macaca mulatta). Four macaques were given PMEA (20 mg/kg) s.c. on days 1 and 2 and inoculated with virus on day 2. Drug treatment was continued for 30 consecutive days, after which the virus burdens and course of infection were monitored for a further 6 mo. Four control animals that did not receive PMEA all developed high virus burdens and two of the four developed clin. disease. In contrast, virus burdens remained low in three of the four macaques treated with PMEA and all four remained healthy. Our results show that suppression of virus replication early in infection can result in reduced virus burdens for a much longer period. .