Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a nonimmunosuppressive cyclosporine analog.

Antimicrobial Agents and Chemotherapy
Brigitte RosenwirthP Peichl

Abstract

(Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppressive activity but retains full capacity for binding to cyclophilin and exhibits potent anti-human immunodeficiency virus type 1 (HIV-1) activity. SDZ NIM 811 selectively inhibits HIV-1 replication in T4 lymphocyte cell lines, in a monocytic cell line, and in HeLa T4 cells. Furthermore, its antiviral activity against laboratory strains and against clinical isolates from geographically distinct regions in primary T4 lymphocytes and in primary monocytes (50% inhibitory concentration = 0.011 to 0.057 micrograms/ml) was demonstrated. SDZ NIM 811 does not inhibit proviral gene expression or virus-specific enzyme functions, either free or bound to cyclophilin. The compound does not influence CD4 expression or inhibit fusion between virus-infected and uninfected cells. SDZ NIM 811 was, however, found to block formation of infectious particles from chronically infected cells. Oral administration to mice, rats, dogs, and monkeys resulted in levels in blood considerably exceeding the drug concentration, which completely blocked virus replication in primary cells. SDZ NIM 811 caused changes of toxicity parameters in rats to a smaller degree t...Continue Reading

References

Jun 1, 1976·The Journal of Experimental Medicine·P RalphK Nilsson
Nov 30, 1992·Annals of the New York Academy of Sciences·F HammerschmidB Rosenwirth
Apr 1, 1992·Journal of Autoimmunity·G BaumannM H Schreier
Sep 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·A KarpasF Hill
Apr 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·G W HoffmannM D Grant
Oct 1, 1990·Antiviral Research·M N Prichard, C Shipman
Mar 1, 1990·Biological Chemistry Hoppe-Seyler·A BillichG Winkler
Aug 1, 1988·Journal of Virological Methods·R PauwelsE De Clercq
Jul 11, 1986·Science·S GartnerM Popovic
May 1, 1988·Clinical Immunology and Immunopathology·J M AndrieuH Sors
Sep 1, 1987·European Journal of Immunology·V F QuesniauxM H Van Regenmortel
Nov 2, 1984·Science·R E HandschumacherD W Speicher
Aug 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·M KrönkeW C Greene
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M I BukrinskyM Stevenson
Apr 1, 1994·Antimicrobial Agents and Chemotherapy·E De ClercqR Datema
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M C HsuM J Potash
Apr 26, 1963·Science·N K Jerne, A A Nordin

❮ Previous
Next ❯

Citations

Jul 26, 1996·Biochemical Pharmacology·T StachelhausM A Marahiel
Dec 4, 2003·Bioorganic & Medicinal Chemistry Letters·Michel EversSerge Mignani
Dec 1, 2007·Nature Reviews. Drug Discovery·Erik De Clercq
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·S R BartzM Malkovsky
Aug 21, 2002·The Journal of Experimental Medicine·Jason A LaBonteJoseph Sodroski
May 13, 2011·The Journal of Pharmacology and Experimental Therapeutics·Benjamin A NacevJun O Liu
Jan 24, 2008·Antimicrobial Agents and Chemotherapy·Roger G PtakBrigitte Rosenwirth
Jun 18, 2010·Journal of Virology·Isabelle DietrichBrian J Willett
Nov 16, 2004·Journal of Virology·Elena SokolskajaJeremy Luban
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·J P LeeR P Roos
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·A A BukovskyH G Göttlinger
Aug 24, 2007·Expert Opinion on Investigational Drugs·Robert FlisiakRaf Crabbé
Sep 4, 2008·Expert Opinion on Emerging Drugs·Erik De Clercq
Sep 26, 1997·FEBS Letters·M A McCornackI M Armitage
Oct 5, 2014·Journal of Molecular and Cellular Cardiology·Muhammad Rizwan AlamMichel Ovize
May 15, 1996·Annals of the New York Academy of Sciences·F HammerschmidB Rosenwirth
Nov 28, 2012·Clinics in Liver Disease·Fernando E MembrenoEric J Lawitz
Oct 28, 2009·Antiviral Research·Dirk DaelemansChristophe Pannecouque
Jul 25, 2009·Clinics in Liver Disease·Philippe A Gallay
May 10, 2005·International Journal of Cancer. Journal International Du Cancer·Iwona CiechomskaBozena Kaminska
Feb 17, 2009·Medicinal Research Reviews·Erik De Clercq
Mar 25, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jan PaeshuyseJohan Neyts
Feb 14, 2006·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·L GomezM Ovize
Oct 9, 2007·Liver International : Official Journal of the International Association for the Study of the Liver·Motoyuki KohjimaMakoto Nakamuta
Jan 6, 2010·Reviews in Medical Virology·Emi E Nakayama, Tatsuo Shioda

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.