Etrog Citron (Citrus medica) as a Novel Source of Antiviral Agents: Overview of Its Bioactive Phytochemicals and Delivery Approaches
Abstract
1. Introduction
2. Methods
3. Antiviral Activity of Phytochemicals
Compound | Structure | Part of the Plant | Virus | Mechanism | References |
---|---|---|---|---|---|
Apigenin | Leaves, flowers, mesocarp, endocarp | BPXV EBV HCV SARS-CoV-2 | Inhibits synthesis of viral DNA, mRNA and proteins, Inhibition of HCV replication | [15,53,54,55] | |
Catechin | Mesocarp, endocarp, seeds, flavedo, pulp | Dengue virus Influenza A (H1N1) | Inhibit a post-entry stage of the DENV replication cycle. Inhibits neuraminidase | [56,57] | |
Caffeic acid | Exocarp, mesocarp, endocarp, seeds | Ilhéus virus Severe fever with thrombocytopenia syndrome (SFTS) | Interacts with the envelope Unknown | [58,59] | |
Chlorogenic acid | Endocarp, mesocarp | Infectious Bursal Disease Virus (IBDV) | Unknown | [60] | |
Dihydroquercetin | Exocarp, endocarp, seeds | Coxsackie B4 virus | Unknown | [61] | |
Diosmin | Flowers, leaves, mesocarp, endocarp | Influenza A, Varicella zoster virus (VZV) | Unknown | [62,63] | |
Epicatechin | Flavedo, pulp | Singapore grouper iridovirus (SGIV) SARS-CoV-2 | Impact on the replication of SGIV, Disrupts the interaction of ACE2 and SARS-CoV-2 | [64,65] | |
Gallic acid | Exocarp, mesocarp, endocarp | Influenza A and B viruses | Unknown | [66] | |
Hesperidin | Flavedo, exocarp, endocarp, mesocarp, seeds, flowers, leaves | SARS-CoV-2 | Inhibition of viral replication | [67] | |
Kaempferol 3-O-rutinoside | Flavedo | HSV-1, HSV-2 SARS-CoV-2 | Unknown | [28,68] | |
Lonchocarpol A | Root, stem | HIV | Unknown | [69] | |
Naringin | Fructus, exocarp, mesocarp, endocarp, seeds, flavedo | Chikungunya virus | Anti-nsP2 protease activity | [70] | |
Neodiosmin | Fructus | SARS-CoV-2 | Unknown | [71] | |
Nobiletin | Exocarp, mesocarp, endocarp, seeds | Chikungunya virus | Translation/replication stages and viral entry | [72] | |
Quercetin | Flowers, leaves, mesocarp, endocarp | SARS-CoV-2 HCV | Suppresses the early phases of infection, interacts with viral replication proteases Inhibits NS3 protease activity | [73,74] | |
Rutin (quercetin-3-rutinoside) | Flavedo | HSV-1, HSV-2 | Unknown | [28] | |
Sakuranetin | Leaves | Human rhinoviruses, Influenza B/Lee/40 virus | Unknown Inhibition of viral RNA synthesis | [75,76] | |
Salicylic acid | Fructus | HSV-1, H1N1 influenza A, adenovirus type 5 | Unknown | [77] | |
Tangeritin | Exocarp, mesocarp, endocarp | RSV | Downregulates expression of RSV phosphoprotein | [78] | |
Vitexin | Exocarp, endocarp, seeds | Influenza A (H1N1) virus HSV-1 HAV | Inflammation reduction Inhibition of viral replication | [79] |
Compound | Structure | Part of the Plant | Virus | Mechanism | References |
---|---|---|---|---|---|
Citropten | Stem, root, barks, fresh fruit | HIV-1 | Unknown | [50] | |
Leptodactylone | Fresh fruit | SARS-CoV-2 | Unknown | [80] | |
Nordentatin | Fresh fruit | HIV-1, Hepatitis B | Unknown | [81,82] | |
Scopoletin | Fresh fruit, fructus | SARS-CoV-2 | Inhibition of virus entry to the host cell | [83,84] | |
Umbelliferone | Fresh fruit | Viral hemorrhagic septicemia virus | Inhibition of VHSV replication, downregulation of Caspase 3 expression and inhibition of virus-induced apoptosis at later infection stages | [85] | |
Xanthyletin | Stem, root, barks, fresh fruit | HIV-1 | Unknown | [50] |
Compound | Structure | Part of the Plant | Virus | Mechanism | References |
---|---|---|---|---|---|
α-pinene | Flavedo | Bronchitis virus | Inhibition of nucleocapsid protein | [86] | |
α-terpineol | Flavedo, fresh fruits, mesocarp | HSV-1 | Unknown | [87] | |
Carvacrol | Flavedo, fresh fruits, mesocarp | HSV-2 Feline calcivirus, Murine norovirus | Inhibits the HSV-2 proliferation Unknown Unknown | [88,89] | |
Citral | Fructus, flavedo, mesocarp | Yellow fever virus | Unknown | [90] | |
Citronellol | Flavedo | HSV-1 | Unknown | [91] | |
Farnesol | Flavedo | HSV-1 | Unknown | [92] | |
Geraniol | Fructus, flavedo | HSV-1 | Changes the subcellular distribution of the oligonucleotides | [93] | |
Limonene | Flavedo, fructus, oil glands, exocarp, mesocarp, seeds | Drug-resistant influenza virus | Inhibition intracellular replication | [94] | |
Limonin | Citron waste, fructus, bark | HIV-1 | Inhibition protease activity | [95] | |
Linalool | Flavedo | AVD-II | Unknown | [96] | |
Nomilin | Fresh fructus | HIV-1 | Inhibition protease activity | [95] | |
Obacunone | Fresh fructus | SARS-CoV-2 | Disruption of target proteins | [97] |
4. Applicability of Delivery Systems
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Dahan, A.; Yarmolinsky, L.; Nakonechny, F.; Semenova, O.; Khalfin, B.; Fleisher-Berkovich, S.; Ben-Shabat, S. Etrog Citron (Citrus medica) as a Novel Source of Antiviral Agents: Overview of Its Bioactive Phytochemicals and Delivery Approaches. Pharmaceutics 2025, 17, 1173. https://doi.org/10.3390/pharmaceutics17091173
Dahan A, Yarmolinsky L, Nakonechny F, Semenova O, Khalfin B, Fleisher-Berkovich S, Ben-Shabat S. Etrog Citron (Citrus medica) as a Novel Source of Antiviral Agents: Overview of Its Bioactive Phytochemicals and Delivery Approaches. Pharmaceutics. 2025; 17(9):1173. https://doi.org/10.3390/pharmaceutics17091173
Chicago/Turabian StyleDahan, Arik, Ludmila Yarmolinsky, Faina Nakonechny, Olga Semenova, Boris Khalfin, Sigal Fleisher-Berkovich, and Shimon Ben-Shabat. 2025. "Etrog Citron (Citrus medica) as a Novel Source of Antiviral Agents: Overview of Its Bioactive Phytochemicals and Delivery Approaches" Pharmaceutics 17, no. 9: 1173. https://doi.org/10.3390/pharmaceutics17091173
APA StyleDahan, A., Yarmolinsky, L., Nakonechny, F., Semenova, O., Khalfin, B., Fleisher-Berkovich, S., & Ben-Shabat, S. (2025). Etrog Citron (Citrus medica) as a Novel Source of Antiviral Agents: Overview of Its Bioactive Phytochemicals and Delivery Approaches. Pharmaceutics, 17(9), 1173. https://doi.org/10.3390/pharmaceutics17091173