Biomaterial Database

Use of a small molecule CCR5 inhibitor in macaques to treat simian immunodeficiency virus infection or prevent simian-human immunodeficiency virus infection. 2003

Ronald S Veazey, and Per Johan Klasse, and Thomas J Ketas, and Jacqueline D Reeves, and Michael Piatak, and Kevin Kunstman, and Shawn E Kuhmann, and Preston A Marx, and Jeffrey D Lifson, and Jason Dufour, and Megan Mefford, and Ivona Pandrea, and Steven M Wolinsky, and Robert W Doms, and Julie A DeMartino, and Salvatore J Siciliano, and Kathy Lyons, and Martin S Springer, and John P Moore

Joan and Sanford I. Weill Medical College of Cornell University, Dept. of Microbiology and Immunology, 1300 York Ave., W-805, New York, NY 10021, USA.

Human immunodeficiency virus type 1 (HIV-1) fuses with cells after sequential interactions between its envelope glycoproteins, CD4 and a coreceptor, usually CC chemokine receptor 5 (CCR5) or CXC receptor 4 (CXCR4). CMPD 167 is a CCR5-specific small molecule with potent antiviral activity in vitro. We show that CMPD 167 caused a rapid and substantial (4-200-fold) decrease in plasma viremia in six rhesus macaques chronically infected with simian immunodeficiency virus (SIV) strains SIVmac251 or SIVB670, but not in an animal infected with the X4 simian-human immunodeficiency virus (SHIV), SHIV-89.6P. In three of the SIV-infected animals, viremia reduction was sustained. In one, there was a rapid, but partial, rebound and in another, there was a rapid and complete rebound. There was a substantial delay (>21 d) between the end of therapy and the onset of full viremia rebound in two animals. We also evaluated whether vaginal administration of gel-formulated CMPD 167 could prevent vaginal transmission of the R5 virus, SHIV-162P4. Complete protection occurred in only 2 of 11 animals, but early viral replication was significantly less in the 11 CMPD 167-recipients than in 9 controls receiving carrier gel. These findings support the development of small molecule CCR5 inhibitors as antiviral therapies, and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission.

UI	MeSH Term	Description	Entries
D008253	Macaca mulatta	A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.	Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014633	Valine	A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.	L-Valine,L Valine
D015302	Simian Immunodeficiency Virus	Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.	SIV (Simian immunodeficiency virus),Immunodeficiency Viruses, Simian,Simian Immunodeficiency Viruses,Immunodeficiency Virus, Simian
D015496	CD4-Positive T-Lymphocytes	A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.	T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016097	Simian Acquired Immunodeficiency Syndrome	Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS.	AIDS, Simian,SAIDS,Simian AIDS,Simian Acquired Immune Deficiency Syndrome,Simian Acquired Immuno-Deficiency Syndrome,AIDSs, Simian,Simian AIDSs,Simian Acquired Immuno Deficiency Syndrome
D044966	Anti-Retroviral Agents	Agents used to treat RETROVIRIDAE INFECTIONS.	Antiretroviral Agent,Antiretroviral Agents,Agent, Antiretroviral,Agents, Anti-Retroviral,Agents, Antiretroviral,Anti Retroviral Agents
D065100	CCR5 Receptor Antagonists	Compounds and drugs that inhibit or block the activity of CCR5 RECEPTORS.	CC Chemokine Receptor 5 Antagonists,CC Chemokine Receptor 5 Blockers,CCR5 Receptor Blockers,Chemokine Co-receptor 5 Antagonists,HIV-1 Fusion Coreceptor Antagonists,Antagonists, CCR5 Receptor,Blockers, CCR5 Receptor,Chemokine Co receptor 5 Antagonists,HIV 1 Fusion Coreceptor Antagonists,Receptor Antagonists, CCR5,Receptor Blockers, CCR5