ArticleACS chemical biology2014
Structural analysis of asunaprevir resistance in HCV NS3/4A protease.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 64 citations in OpenAlex.
- Combined crystallographic fragment screening and deep mutational scanning enable discovery of Zika virus NS2B-NS3 protease inhibitors.Nature communications · 2025Article
- Article
- Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs.Molecules (Basel, Switzerland) · 2023Article
- Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections.Diagnostics (Basel, Switzerland) · 2023Article
- Structural and Synthetic Aspects of Small Ring Oxa- and Aza-Heterocyclic Ring Systems as Antiviral Activities.Viruses · 2023Review
- Going Viral: An Investigation into the Chameleonic Behaviour of Antiviral Compounds.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Deciphering the Molecular Mechanism of HCV Protease Inhibitor Fluorination as a General Approach to Avoid Drug Resistance.Journal of molecular biology · 2022Article
- Asunaprevir, a Potent Hepatitis C Virus Protease Inhibitor, Blocks SARS-CoV-2 Propagation.Molecules and cells · 2021Article
- Viral proteases: Structure, mechanism and inhibition.The Enzymes · 2021Article
- Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease.Nature communications · 2020Article
- Article
- Molecular and Structural Mechanism of Pan-Genotypic HCV NS3/4A Protease Inhibition by Glecaprevir.ACS chemical biology · 2020Article
- Discovery of New Inhibitors of Hepatitis C Virus NS3/4A Protease and Its D168A Mutant.ACS omega · 2019Article
- Multi-input chemical control of protein dimerization for programming graded cellular responses.Nature biotechnology · 2019Article
- Resistance outside the substrate envelope: hepatitis C NS3/4A protease inhibitors.Critical reviews in biochemistry and molecular biology · 2019Review
- Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure.Infection · 2018Review
- Molecular Mechanism of Resistance in a Clinically Significant Double-Mutant Variant of HCV NS3/4A Protease.Structure (London, England : 1993) · 2018Article
- StaPLs: versatile genetically encoded modules for engineering drug-inducible proteins.Nature methods · 2018Article
- UsingACS medicinal chemistry letters · 2018Article
- Pharmacophore anchor models of flaviviral NS3 proteases lead to drug repurposing for DENV infection.BMC bioinformatics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Asunaprevir (ASV), an isoquinoline-based competitive inhibitor targeting the hepatitis C virus (HCV) NS3/4A protease, is very potent in vivo. However, the potency is significantly compromised by the drug resistance mutations R155K and D168A. In this study three crystal structures of ASV and an analogue were determined to analyze the structural basis of drug resistance susceptibility. These structures revealed that ASV makes extensive contacts with Arg155 outside the substrate envelope. Arg155 in turn is stabilized by Asp168, and thus when either residue is mutated, the enzyme's interaction with ASV's P2* isoquinoline is disrupted. Adding a P1-P3 macrocycle to ASV enhances the inhibitor's resistance barrier, likely due to poising the inhibitor to its bound conformation. Macrocyclic inhibitors with P2* extension moieties avoiding interaction with the protease S2 residues including Arg155 must be chosen for future design of more robust protease inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.