Resistance to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives is generated by mutations at multiple sites in the HIV-1 reverse transcriptase

Virology
R W BuckheitJ P Bader

Abstract

Virus isolates resistant to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and a highly potent HEPT derivative, [1-benzyloxymethyl-5-ethyl-6-(alpha-pyridylthio)uracil] (NSC 648400, E-BPTU), were selected in cell culture. Cross-resistance evaluation indicated that the two drug-resistant virus isolates were phenotypically distinct from one another although each of the virus isolates was resistant to both of the HEPT derivatives. The virus isolate resistant to NSC 648400 had a single amino acid change in the reverse transcriptase (Y181C) which resulted in cross-resistance to all of the nonnucleoside reverse transcriptase inhibitors evaluated, with the exception of calanolide A. The NSC 648400-resistant virus isolate exhibited 15-fold enhanced sensitivity to calanolide A. The virus isolate selected in the presence of HEPT exhibited a single amino acid change (P236L) which was not cross-resistant to other nonnucleoside RT inhibitors tested with the exception of the two HEPT derivatives. This HEPT-resistant virus isolate exhibited enhanced sensitivity (5- to 10-fold) to thiazolobenzimidazole. We have used both virus isolates with defined single amino acid changes in the RT and bacterially expressed RTs with site-directed am...Continue Reading

Citations

Sep 2, 2004·Biological & Pharmaceutical Bulletin·Maira Huerta-ReyesRicardo Reyes-Chilpa
Jul 2, 2005·Expert Opinion on Emerging Drugs·M L AndreolaM Legraverend
Feb 3, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Shreekant DeshpandeYenamandra S Prabhakar
Nov 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lutfun NaharSatyajit D Sarker

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allergy & Infectious Diseases

Allergies result from the hyperreactivity of the immune system to some environmental substance and can be life-threatening. Infectious diseases are caused by organisms including bacteria, viruses, fungi and parasites. They can be transmitted different ways, such as person-to-person. Here is the latest research on allergy and infectious diseases.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Allergy & Infectious Diseases (ASM)

Allergies result from the hyperreactivity of the immune system to some environmental substance and can be life-threatening. Infectious diseases are caused by organisms including bacteria, viruses, fungi and parasites. They can be transmitted different ways, such as person-to-person. Here is the latest research on allergy and infectious diseases.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

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.