Inhibition profiling of retroviral protease inhibitors using an HIV-2 modular system

Mohamed Mahdi, Zsófia Szojka, János András Mótyán, J. Tőzsér

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Retroviral protease inhibitors (PIs) are fundamental pillars in the treatment of HIV infection and acquired immunodeficiency syndrome (AIDS). Currently used PIs are designed against HIV-1, and their effect on HIV-2 is understudied. Using a modular HIV-2 protease cassette system, inhibition profiling assays were carried out for protease inhibitors both in enzymatic and cell culture assays. Moreover, the treatment-associated resistance mutations (I54M, L90M) were introduced into the modular system, and comparative inhibition assays were performed to determine their effect on the susceptibility of the protease. Our results indicate that darunavir, saquinavir, indinavir and lopinavir were very effective HIV-2 protease inhibitors, while tipranavir, nelfinavir and amprenavir showed a decreased efficacy. I54M, L90M double mutation resulted in a significant reduction in the susceptibility to most of the inhibitors with the exception of tipranavir. To our knowledge, this modular system constitutes a novel approach in the field of HIV-2 protease characterization and susceptibility testing.

Original languageEnglish
Pages (from-to)6152-6162
Number of pages11
JournalViruses
Volume7
Issue number12
DOIs
Publication statusPublished - Nov 27 2015

Fingerprint

HIV-2
Protease Inhibitors
Nelfinavir
Saquinavir
Lopinavir
Indinavir
HIV Protease Inhibitors
Mutation
HIV Infections
HIV-1
Acquired Immunodeficiency Syndrome
Peptide Hydrolases
Cell Culture Techniques
Human immunodeficiency virus 2 p16 protease
tipranavir

Keywords

  • HIV-2
  • Modular system
  • Protease
  • Protease inhibitors
  • Susceptibility

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

Inhibition profiling of retroviral protease inhibitors using an HIV-2 modular system. / Mahdi, Mohamed; Szojka, Zsófia; Mótyán, János András; Tőzsér, J.

In: Viruses, Vol. 7, No. 12, 27.11.2015, p. 6152-6162.

Research output: Contribution to journalArticle

Mahdi, Mohamed ; Szojka, Zsófia ; Mótyán, János András ; Tőzsér, J. / Inhibition profiling of retroviral protease inhibitors using an HIV-2 modular system. In: Viruses. 2015 ; Vol. 7, No. 12. pp. 6152-6162.
@article{081424f108654cd1b9a22b95a925a616,
title = "Inhibition profiling of retroviral protease inhibitors using an HIV-2 modular system",
abstract = "Retroviral protease inhibitors (PIs) are fundamental pillars in the treatment of HIV infection and acquired immunodeficiency syndrome (AIDS). Currently used PIs are designed against HIV-1, and their effect on HIV-2 is understudied. Using a modular HIV-2 protease cassette system, inhibition profiling assays were carried out for protease inhibitors both in enzymatic and cell culture assays. Moreover, the treatment-associated resistance mutations (I54M, L90M) were introduced into the modular system, and comparative inhibition assays were performed to determine their effect on the susceptibility of the protease. Our results indicate that darunavir, saquinavir, indinavir and lopinavir were very effective HIV-2 protease inhibitors, while tipranavir, nelfinavir and amprenavir showed a decreased efficacy. I54M, L90M double mutation resulted in a significant reduction in the susceptibility to most of the inhibitors with the exception of tipranavir. To our knowledge, this modular system constitutes a novel approach in the field of HIV-2 protease characterization and susceptibility testing.",
keywords = "HIV-2, Modular system, Protease, Protease inhibitors, Susceptibility",
author = "Mohamed Mahdi and Zs{\'o}fia Szojka and M{\'o}ty{\'a}n, {J{\'a}nos Andr{\'a}s} and J. Tőzs{\'e}r",
year = "2015",
month = "11",
day = "27",
doi = "10.3390/v7122931",
language = "English",
volume = "7",
pages = "6152--6162",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "12",

}

TY - JOUR

T1 - Inhibition profiling of retroviral protease inhibitors using an HIV-2 modular system

AU - Mahdi, Mohamed

AU - Szojka, Zsófia

AU - Mótyán, János András

AU - Tőzsér, J.

PY - 2015/11/27

Y1 - 2015/11/27

N2 - Retroviral protease inhibitors (PIs) are fundamental pillars in the treatment of HIV infection and acquired immunodeficiency syndrome (AIDS). Currently used PIs are designed against HIV-1, and their effect on HIV-2 is understudied. Using a modular HIV-2 protease cassette system, inhibition profiling assays were carried out for protease inhibitors both in enzymatic and cell culture assays. Moreover, the treatment-associated resistance mutations (I54M, L90M) were introduced into the modular system, and comparative inhibition assays were performed to determine their effect on the susceptibility of the protease. Our results indicate that darunavir, saquinavir, indinavir and lopinavir were very effective HIV-2 protease inhibitors, while tipranavir, nelfinavir and amprenavir showed a decreased efficacy. I54M, L90M double mutation resulted in a significant reduction in the susceptibility to most of the inhibitors with the exception of tipranavir. To our knowledge, this modular system constitutes a novel approach in the field of HIV-2 protease characterization and susceptibility testing.

AB - Retroviral protease inhibitors (PIs) are fundamental pillars in the treatment of HIV infection and acquired immunodeficiency syndrome (AIDS). Currently used PIs are designed against HIV-1, and their effect on HIV-2 is understudied. Using a modular HIV-2 protease cassette system, inhibition profiling assays were carried out for protease inhibitors both in enzymatic and cell culture assays. Moreover, the treatment-associated resistance mutations (I54M, L90M) were introduced into the modular system, and comparative inhibition assays were performed to determine their effect on the susceptibility of the protease. Our results indicate that darunavir, saquinavir, indinavir and lopinavir were very effective HIV-2 protease inhibitors, while tipranavir, nelfinavir and amprenavir showed a decreased efficacy. I54M, L90M double mutation resulted in a significant reduction in the susceptibility to most of the inhibitors with the exception of tipranavir. To our knowledge, this modular system constitutes a novel approach in the field of HIV-2 protease characterization and susceptibility testing.

KW - HIV-2

KW - Modular system

KW - Protease

KW - Protease inhibitors

KW - Susceptibility

UR - http://www.scopus.com/inward/record.url?scp=84949219020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949219020&partnerID=8YFLogxK

U2 - 10.3390/v7122931

DO - 10.3390/v7122931

M3 - Article

C2 - 26633459

AN - SCOPUS:84949219020

VL - 7

SP - 6152

EP - 6162

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 12

ER -