ArticleGenes & development2007
Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance.
Article in Genes & development, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
What it found
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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.
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Who cites it
145 citing papers in PubMed, 265 citations in OpenAlex.
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- Infection-specific long-chain fatty acid metabolism as a broad anti-enterovirus target.bioRxiv : the preprint server for biology · 2026Article
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- Host species-specific mutations in the thumb domain of the 3Dpol polymerase are required for efficient replication of human hepatitis A virus in mice.PLoS pathogens · 2026Article
- Divergent roles of Hsp70 chaperones in orthoflavivirus protein secretion and virion formation.Npj viruses · 2026Article
- Heat shock protein 90 chaperone activity is required for hepatitis A virus replication.Journal of virology · 2025Article
- A Fluorescent Reporter Virus Toolkit for Interrogating Enterovirus Biology and Host Interactions.Viruses · 2025Article
- Molecular mechanisms of the viral encoded chaperone 100K in capsid folding and assembly of adenovirus.Nature communications · 2025Article
- Hsp70-Hsp90 organising protein (HOP/STIP1) is required for KSHV lytic replication.The Journal of general virology · 2024Article
- HSP70 positively regulates translation by interacting with the IRES and stabilizes the viral structural proteins VP1 and VP3 to facilitate duck hepatitis A virus type 1 replication.Veterinary research · 2024Article
- HSP90 is part of a protein complex with the L polymerase of Rift Valley fever phlebovirus and prevents its degradation by the proteasome during the viral genome replication/transcription stage.Frontiers in cellular and infection microbiology · 2024Article
- Differential inhibition of intra- and inter-molecular protease cleavages by antiviral compounds.Journal of virology · 2023Article
- The Picornaviridae Family: Knowledge Gaps, Animal Models, Countermeasures, and Prototype Pathogens.The Journal of infectious diseases · 2023Article
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- The development of resistance to an inhibitor of a cellular protein reveals a critical interaction between the enterovirus protein 2C and a small GTPase Arf1.PLoS pathogens · 2023Article
- Inhibition of Human Coronaviruses by Combinations of Host-Targeted and Direct-Acting Antivirals.Antimicrobial agents and chemotherapy · 2023Article
- Article
- Review
- Direct-Acting Antivirals and Host-Targeting Approaches against Enterovirus B Infections: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2023Review
85 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The genome diversity of RNA viruses allows for rapid adaptation to a wide variety of adverse conditions. Accordingly, viruses can escape inhibition by most antiviral compounds targeting either viral or host factors. Here we exploited the capacity of RNA viruses for rapid adaptation to explore the evolutionary constraints of chaperone-mediated protein folding. We hypothesized that inhibiting a host molecular chaperone required for folding of a viral protein would force the virus to evolve an alternate folding strategy. We identified the chaperone Hsp90 as an essential factor for folding and maturation of picornavirus capsid proteins. Pharmacological inhibition of Hsp90 impaired the replication of poliovirus, rhinovirus, and coxsackievirus in cell culture. Strikingly, anti-Hsp90 treatment did not yield drug-resistant viruses, suggesting that the complexity of capsid folding precludes the emergence of alternate folding pathways. These results reveal tight evolutionary constraints on chaperone-mediated protein folding, which may be exploited for viral inhibition in vivo. Indeed, Hsp90 inhibitors drastically reduced poliovirus replication in infected animals without the emergence of drug-resistant escape mutants. We propose that targeting folding of viral proteins may provide a general antiviral strategy that is refractory to development of drug resistance.
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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.