Targeting HIV-1 Reverse Transcriptase Using a Fragment-Based Approach.

HIV-1 drug discovery fragment-based drug design non-nucleoside reverse transcriptase inhibitors (NNRTIs) reverse transcriptase

Journal

Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009

Informations de publication

Date de publication:
30 Mar 2023
Historique:
received: 28 12 2022
revised: 24 03 2023
accepted: 24 03 2023
medline: 14 4 2023
entrez: 13 4 2023
pubmed: 14 4 2023
Statut: epublish

Résumé

Human immunodeficiency virus type I (HIV-1) is a retrovirus that infects cells of the host's immune system leading to acquired immunodeficiency syndrome and potentially death. Although treatments are available to prevent its progression, HIV-1 remains a major burden on health resources worldwide. Continued emergence of drug-resistance mutations drives the need for novel drugs that can inhibit HIV-1 replication through new pathways. The viral protein reverse transcriptase (RT) plays a fundamental role in the HIV-1 replication cycle, and multiple approved medications target this enzyme. In this study, fragment-based drug discovery was used to optimize a previously identified hit fragment (compound

Identifiants

pubmed: 37049868
pii: molecules28073103
doi: 10.3390/molecules28073103
pmc: PMC10095864
pii:
doi:

Substances chimiques

reverse transcriptase, Human immunodeficiency virus 1 EC 2.7.7.-
Reverse Transcriptase Inhibitors 0
HIV Reverse Transcriptase EC 2.7.7.49
Anti-HIV Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIGMS NIH HHS
ID : T32 GM135141
Pays : United States

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Auteurs

Mahta Mansouri (M)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Shawn Rumrill (S)

Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.

Shane Dawson (S)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Adam Johnson (A)

Retroviral Biology and Antivirals Laboratory, Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, VIC 3004, Australia.

Jo-Anne Pinson (JA)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Menachem J Gunzburg (MJ)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Catherine F Latham (CF)

Retroviral Biology and Antivirals Laboratory, Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, VIC 3004, Australia.

Nicholas Barlow (N)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

George W Mbogo (GW)

Retroviral Biology and Antivirals Laboratory, Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, VIC 3004, Australia.

Paula Ellenberg (P)

Retroviral Biology and Antivirals Laboratory, Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, VIC 3004, Australia.

Stephen J Headey (SJ)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Nicolas Sluis-Cremer (N)

Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

David Tyssen (D)

Retroviral Biology and Antivirals Laboratory, Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, VIC 3004, Australia.

Joseph D Bauman (JD)

Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.

Francesc X Ruiz (FX)

Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.

Eddy Arnold (E)

Center for Advanced Biotechnology and Medicine, Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.

David K Chalmers (DK)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

Gilda Tachedjian (G)

Retroviral Biology and Antivirals Laboratory, Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, VIC 3004, Australia.
Department of Microbiology, Monash University, Clayton, VIC 3168, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.

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Classifications MeSH