ArticlePloS one2021
In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Scorpion Peptides in Antiviral Drug Discovery: An In-depth Review.Probiotics and antimicrobial proteins · 2026Review
- Recent advances in antiviral drugs for Chikungunya virus (CHIKV): Targets, mechanisms, and development strategies.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Protease Inhibitors and Innate Immune Agonists as Antiviral Strategies Against Dengue and Zika Viruses.Pathogens (Basel, Switzerland) · 2026Review
- Inhibition of Chikungunya virus nsP2 protease in vitro by scorpion venom peptide pantinin-1.PloS one · 2026Article
- Single-stranded nucleic acid binding enhances the in vitro catalytic activity of Chikungunya virus nsP2 protease.BBA advances · 2026Article
- In vitro evaluation of the anthelmintic activity of citrus flavonoids against free-living and parasitic nematodes.Scientific reports · 2025Article
- Biodiversity to Breakthroughs: The Promise of Saudi Arabian Medicinal Plants in Antiviral Research.Applied biochemistry and biotechnology · 2025Review
- Antiviral Activity of Glucosyl Hesperidin Against Feline Calicivirus.Microorganisms · 2025Article
- Flavonoids as Immunoregulators: Molecular Mechanisms in Regulating Immune Cells and Their Therapeutic Applications in Inflammatory Diseases.Frontiers in immunology · 2025Review
- Novel peptide inhibitor for the Chikungunya virus nsP2 protease: Identification and characterization.Current research in microbial sciences · 2025Article
- HR-MAS NMR Metabolomics Profile of Vero Cells under the Influence of Virus Infection and nsP2 Inhibitor: A Chikungunya Case Study.International journal of molecular sciences · 2024Article
- Natural Products and Derivatives as PotentialViruses · 2023Review
- Pharmacologic Comparison of High-Dose Hesperetin and Quercetin on MDCK II Cell Viability, Tight Junction Integrity, and Cell Shape.Antioxidants (Basel, Switzerland) · 2023Article
- The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses.Pharmaceutics · 2023Article
- Structural insights into the inhibition of the nsP2 protease from Chikungunya virus by molecular modeling approaches.Journal of molecular modeling · 2022Article
- Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases.Microorganisms · 2022Article
- A review on structural genomics approach applied for drug discovery against three vector-borne viral diseases: Dengue, Chikungunya and Zika.Virus genes · 2022Review
- Nanotechnology Applications of Flavonoids for Viral Diseases.Pharmaceutics · 2021Review
- Promising Natural Compounds against Flavivirus Proteases: Citrus Flavonoids Hesperetin and Hesperidin.Plants (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genus Alphavirus), dengue virus (DENV, genus Flavivirus), and zika virus (ZIKV, genus Flavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection. The results described in our study demonstrate the inhibitory potential of two flavonoids derived from citrus plants: Hesperetin (HST) against NS2B/NS3pro of ZIKV and nsP2pro of CHIKV and, Hesperidin (HSD) against nsP2pro of CHIKV. The flavonoids are noncompetitive inhibitors and the determined IC50 values are in low µM range for HST against ZIKV NS2B/NS3pro (12.6 ± 1.3 µM) and against CHIKV nsP2pro (2.5 ± 0.4 µM). The IC50 for HSD against CHIKV nsP2pro was 7.1 ± 1.1 µM. The calculated ligand efficiencies for HST were > 0.3, which reflect its potential to be used as a lead compound. Docking and molecular dynamics simulations display the effect of HST and HSD on the protease 3D models of CHIKV and ZIKV. Conformational changes after ligand binding and their effect on the substrate-binding pocket of the proteases were investigated. Additionally, MTT assays demonstrated a very low cytotoxicity of both the molecules. Based on our results, we assume that HST comprise a chemical structure that serves as a starting point molecule to develop a potent inhibitor to combat CHIKV and ZIKV co-infections by inhibiting the virus proteases.
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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.