Phosphorothioate 2' deoxyribose oligomers as microbicides that inhibit human immunodeficiency virus type 1 (HIV-1) infection and block Toll-like receptor 7 (TLR7) and TLR9 triggering by HIV-1.

Antimicrobial Agents and Chemotherapy
Joseph A FraiettaP D Katsikis

Abstract

Topical microbicides may prove to be an important strategy for preventing human immunodeficiency virus type 1 (HIV-1) transmission. We examined the safety and efficacy of sequence-nonspecific phosphorothioate 2' deoxyribose oligomers as potential novel microbicides. A short, 13-mer poly(T) phosphorothioate oligodeoxynucleotide (OPB-T) significantly inhibited infection of primary peripheral blood mononuclear cells (PBMC) by high-titer HIV-1(Ba-L) and simian immunodeficiency virus mac251 (SIV(mac251)). Continuous exposure of human vaginal and foreskin tissue explants to OPB-T showed no toxicity. An abasic 14-mer phosphorothioate 2' deoxyribose backbone (PDB) demonstrated enhanced anti-HIV-1 activity relative to OPB-T and other homo-oligodeoxynucleotide analogs. When PDB was used to pretreat HIV-1, PDB was effective against R5 and X4 isolates at a half-maximal inhibitory concentration (IC(50)) of <1 μM in both PBMC and P4-R5 MAGI cell infections. PDB also reduced HIV-1 infectivity following the binding of virus to target cells. This novel topical microbicide candidate exhibited an excellent in vitro safety profile in human PBMC and endocervical epithelial cells. PDB also retained activity in hydroxyethylcellulose gel at pH 4.4 and...Continue Reading

References

Aug 1, 1988·Journal of Virological Methods·R PauwelsE De Clercq
Jan 1, 1983·Acta Obstetricia Et Gynecologica Scandinavica·S BjerckeE Thorsby
Sep 2, 1994·Journal of Molecular Biology·P CharneauF Clavel
Feb 1, 1994·AIDS Research and Human Retroviruses·M G LewisG A Eddy
Oct 27, 1998·AIDS Research and Human Retroviruses·M GirardP N Fultz
Jan 30, 1999·Antimicrobial Agents and Chemotherapy·M K HowettJ W Kreider
Jan 24, 2002·The Journal of Clinical Investigation·Kristen V KhannaRichard B Markham
Jul 5, 2003·Journal of Clinical Microbiology·L K Rabe, S L Hillier
Sep 3, 2004·The Journal of Clinical Investigation·Vincent Piguet, Quentin Sattentau
Jul 5, 2005·Journal of Virology·Christopher J MillerAshley T Haase
Oct 4, 2005·Nature Reviews. Immunology·Marko Salmi, Sirpa Jalkanen
Oct 4, 2005·Nature Reviews. Immunology·Ashley T Haase
Oct 15, 2005·The Journal of Clinical Investigation·Anne-Sophie BeignonNina Bhardwaj
Dec 3, 2005·The Journal of Infectious Diseases·Darpun Dhawan, Kenneth H Mayer
Apr 28, 2006·Nature Reviews. Immunology·Michael M LedermanOliver Hartley
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Keith K B GordenSefik S Alkan
Nov 21, 2007·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Liesbeth J M BollenJanet M McNicholl
May 16, 2008·Nature·Anthony S Fauci
Jul 4, 2008·Retrovirology·Enrico IaccinoGiuseppe Scala
Jan 14, 2009·Antimicrobial Agents and Chemotherapy·R T TrifonovaR N Fichorova
Feb 6, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Joseph A PolitchDeborah J Anderson
Mar 6, 2009·Nature·Qingsheng LiAshley T Haase

❮ Previous
Next ❯

Citations

Jan 14, 2012·Journal of Medicinal Chemistry·Nikunj M ShuklaSunil A David
Jan 16, 2013·AIDS Research and Human Retroviruses·Maarten BuitendijkAlexandra L Howell
Nov 23, 2011·Bioorganic & Medicinal Chemistry Letters·Rehman UkaniSunil A David
Nov 8, 2019·Organic & Biomolecular Chemistry·Rakhee ChoudharySatpal Singh Badsara
Jul 8, 2011·Current Opinion in HIV and AIDS·Rada EllegårdMarie Larsson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

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

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 (ASM)

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