# Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics.
> フルオロオレフィン系γターン模倣体によるC型肝炎ウイルスNS5Aの阻害


## Abstract

HCV non-structural protein NS5A represents an important antiviral drug target. Computational modeling revealed that strong intramolecular hydrogen bonds constitute a shared structural feature among potent NS5A inhibitors with low picomolar replicon activity. Based on this finding, a novel inhibitor incorporating a fluoro-olefin isostere was designed to replicate gamma-turn-like substructures. The resulting compound demonstrated picomolar potency against HCV genotype 1b replicon (EC50 = 79 pM) with no detectable cytotoxicity. This activity level is comparable to peptide-based clinical candidates, supporting the utility of peptidomimetic strategies for generating structurally distinct and highly potent NS5A inhibitors.

### Mechanism

A fluoro-olefin isostere mimics the gamma-turn substructure present in potent NS5A inhibitors, reproducing key intramolecular hydrogen bonds that confer picomolar antiviral activity against HCV genotype 1b replicon.

## Bibliographic

- **Authors**: Chang W, Mosley RT, Bansal S, Keilman M, Lam AM, Furman PA, et al.
- **Journal**: Bioorg Med Chem Lett
- **Year**: 2012 (2012-04-15)
- **PMID**: [22425564](https://pubmed.ncbi.nlm.nih.gov/22425564/)
- **DOI**: [10.1016/j.bmcl.2012.02.051](https://doi.org/10.1016/j.bmcl.2012.02.051)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 22425564. https://h2-papers.org/en/papers/22425564
> **Source**: PubMed PMID [22425564](https://pubmed.ncbi.nlm.nih.gov/22425564/)