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Viruses
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Recent Advances in Antiviral Natural Products
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Recent Advances in Antiviral Natural Products

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 12305

Special Issue Editor

Prof. Dr. Jin-ching Lee

E-Mail Website
Guest Editor
Department of Marine Biotechnology and Resoures, National Sun Yat-Sen University, NSYSU, Kaohsiung, Taiwan
Interests: virology; liver cancer; biotechnology; molecular cytology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products (NPs) extracted from medicinal plants and marine life have been suggested as excellent sources for the development of novel pharmaceuticals. In past years, many NPs have been identified to target the viral life cycle, including viral entry, replication, assembly, and release. In addition, host factors associated with viral infection have also been identified as novel targets of NPs. Particularly, NPs with antiviral and immune-modulation activities are potential agents against emerging COVID-19 infectious diseases.

For this Special Issue, we welcome contributions directed at the discovery of antiviral natural products, as well as at mechanistic studies of extracts and NPs against viruses.

Prof. Dr. Jin-ching Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural products
  • antivirals
  • drug screening
  • immune-modulation
  • viral life cycle

Published Papers (6 papers)

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Research

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15 pages, 2594 KiB  
Article
Grape Seed Proanthocyanidins Inhibit Replication of the Dengue Virus by Targeting NF-kB and MAPK-Mediated Cyclooxygenase-2 Expression
by Wei-Chun Chen, Monir Hossen, Wangta Liu, Chia-Hung Yen, Chung-Hao Huang, Yao-Chin Hsu and Jin-Ching Lee
Viruses 2023, 15(4), 884; https://doi.org/10.3390/v15040884 - 30 Mar 2023
Cited by 4 | Viewed by 1876
Abstract
Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do [...] Read more.
Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Natural Products)
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16 pages, 5959 KiB  
Article
Heparan Sulfate and Enoxaparin Interact at the Interface of the Spike Protein of HCoV-229E but Not with HCoV-OC43
by Virginia Fuochi, Giuseppe Floresta, Rosalia Emma, Vincenzo Patamia, Massimo Caruso, Chiara Zagni, Federica Ronchi, Celestino Ronchi, Filippo Drago, Antonio Rescifina and Pio Maria Furneri
Viruses 2023, 15(3), 663; https://doi.org/10.3390/v15030663 - 01 Mar 2023
Cited by 3 | Viewed by 1515
Abstract
It is known that the spike protein of human coronaviruses can bind to a secondary receptor, or coreceptor, to facilitate the virus entry. While HCoV-229E uses human aminopeptidase N (hAPN) as a receptor, HCoV-OC43 binds to 9-O-acetyl-sialic acid (9-O-Ac-Sia), [...] Read more.
It is known that the spike protein of human coronaviruses can bind to a secondary receptor, or coreceptor, to facilitate the virus entry. While HCoV-229E uses human aminopeptidase N (hAPN) as a receptor, HCoV-OC43 binds to 9-O-acetyl-sialic acid (9-O-Ac-Sia), which is linked in a terminal way to the oligosaccharides that decorate glycoproteins and gangliosides on the surface of the host cell. Thus, evaluating the possible inhibitory activity of heparan sulfate, a linear polysaccharide found in animal tissues, and enoxaparin sodium on these viral strains can be considered attractive. Therefore, our study also aims to evaluate these molecules’ antiviral activity as possible adsorption inhibitors against non-SARS-CoV. Once the molecules’ activity was verified in in vitro experiments, the binding was studied by molecular docking and molecular dynamic simulations confirming the interactions at the interface of the spike proteins. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Natural Products)
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19 pages, 3091 KiB  
Article
Punica granatum Peel and Leaf Extracts as Promising Strategies for HSV-1 Treatment
by Asma EL-Aguel, Rosamaria Pennisi, Antonella Smeriglio, Imen Kallel, Maria Pia Tamburello, Manuela D’Arrigo, Davide Barreca, Ahmed Gargouri, Domenico Trombetta, Giuseppina Mandalari and Maria Teresa Sciortino
Viruses 2022, 14(12), 2639; https://doi.org/10.3390/v14122639 - 26 Nov 2022
Cited by 8 | Viewed by 1460
Abstract
Punica granatum is a rich source of bioactive compounds which exhibit various biological effects. In this study, pomegranate peel and leaf ethanolic crude extracts (PPE and PLE, respectively) were phytochemically characterized and screened for antioxidant, antimicrobial and antiviral activity. LC-PDA-ESI-MS analysis led to [...] Read more.
Punica granatum is a rich source of bioactive compounds which exhibit various biological effects. In this study, pomegranate peel and leaf ethanolic crude extracts (PPE and PLE, respectively) were phytochemically characterized and screened for antioxidant, antimicrobial and antiviral activity. LC-PDA-ESI-MS analysis led to the identification of different compounds, including ellagitannins, flavonoids and phenolic acids. The low IC50 values, obtained by DPPH and FRAP assays, showed a noticeable antioxidant effect of PPE and PLE comparable to the reference standards. Both crude extracts and their main compounds (gallic acid, ellagic acid and punicalagin) were not toxic on Vero cells and exhibited a remarkable inhibitory effect on herpes simplex type 1 (HSV-1) viral plaques formation. Specifically, PPE inhibited HSV-1 adsorption to the cell surface more than PLE. Indeed, the viral DNA accumulation, the transcription of viral genes and the expression of viral proteins were significantly affected by PPE treatment. Amongst the compounds, punicalagin, which is abundant in PPE crude extract, inhibited HSV-1 replication, reducing viral DNA and transcripts accumulation, as well as proteins of all three phases of the viral replication cascade. In contrast, no antibacterial activity was detected. In conclusion, our findings indicate that Punica granatum peel and leaf extracts, especially punicalagin, could be a promising therapeutic candidate against HSV-1. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Natural Products)
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15 pages, 7219 KiB  
Article
Antiviral Activity of Ficus rubiginosa Leaf Extracts against HSV-1, HCoV-229E and PV-1
by Federica Dell’Annunziata, Carmine Sellitto, Gianluigi Franci, Maria Carla Marcotullio, Anna Piovan, Roberta Della Marca, Veronica Folliero, Massimiliano Galdiero, Amelia Filippelli, Valeria Conti and Domenico Vittorio Delfino
Viruses 2022, 14(10), 2257; https://doi.org/10.3390/v14102257 - 14 Oct 2022
Cited by 4 | Viewed by 1535
Abstract
Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, [...] Read more.
Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, and Poliovirus-1 (PV-1) was investigated in the different phases of viral infection in the VERO CCL-81 cell line. To confirm the antiviral efficacy, a qPCR was conducted. The recorded cytotoxic concentration 50% was 513.1, 298.6, and 56.45 µg/mL for MeOH, H, and EA, respectively, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay after 72 h of treatment. The Ficus rubiginosa leaf extract inhibited the replication of HSV-1 in the early stages of infection, showing a complete inhibition up to 0.62, 0.31, and 1.25 µg/mL. Against HCoV-229E, a total inhibition up to 1.25 µg/mL for MeOH and H as well as 5 µg/mL for EA was observed. Otherwise, no activity was recorded against PV-1. The leaf extract could act directly on the viral envelope, destructuring the lipid membrane and/or directly blocking the enriched proteins on the viral surface. The verified gene inhibition suggested that the treatments with M, H, and EA impaired HSV-1 and HCoV-229E replication, with a greater antiviral efficiency against HSV-1 compared to HCoV-229E, possibly due to a greater affinity of Ficus rubiginosa towards membrane glycoproteins and/or the different lipid envelopes. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Natural Products)
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Review

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32 pages, 1388 KiB  
Review
Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review
by Rosângela Santos Pereira, Françoise Camila Pereira Santos, Priscilla Rodrigues Valadares Campana, Vivian Vasconcelos Costa, Rodrigo Maia de Pádua, Daniele G. Souza, Mauro Martins Teixeira and Fernão Castro Braga
Viruses 2023, 15(5), 1211; https://doi.org/10.3390/v15051211 - 20 May 2023
Cited by 7 | Viewed by 2726
Abstract
Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants [...] Read more.
Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Natural Products)
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15 pages, 2469 KiB  
Review
Broad-Spectrum Antivirals Derived from Natural Products
by Wen-Jun Tian and Xiao-Jia Wang
Viruses 2023, 15(5), 1100; https://doi.org/10.3390/v15051100 - 30 Apr 2023
Viewed by 2270
Abstract
Scientific advances have led to the development and production of numerous vaccines and antiviral drugs, but viruses, including re-emerging and emerging viruses, such as SARS-CoV-2, remain a major threat to human health. Many antiviral agents are rarely used in clinical treatment, however, because [...] Read more.
Scientific advances have led to the development and production of numerous vaccines and antiviral drugs, but viruses, including re-emerging and emerging viruses, such as SARS-CoV-2, remain a major threat to human health. Many antiviral agents are rarely used in clinical treatment, however, because of their inefficacy and resistance. The toxicity of natural products may be lower, and some natural products have multiple targets, which means less resistance. Therefore, natural products may be an effective means to solve virus infection in the future. New techniques and ideas are currently being developed for the design and screening of antiviral drugs thanks to recent revelations about virus replication mechanisms and the advancement of molecular docking technology. This review will summarize recently discovered antiviral drugs, mechanisms of action, and screening and design strategies for novel antiviral agents. Full article
(This article belongs to the Special Issue Recent Advances in Antiviral Natural Products)
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