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Natural Products against Viral Infections
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Natural Products against Viral Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (28 February 2019) | Viewed by 39643

Special Issue Editor

Prof. Dr. William N. Setzer

E-Mail Website
Guest Editor
Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA
Interests: natural product drug discovery; essential oils; chemical ecology; molecular modeling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Although immunization against viral infections has reduced or eradicated several viral diseases, including smallpox, polio, and measles, viral infections continue to be a source of human morbidity and mortality. Antiviral drug resistance has been emerging and viral mutations present new problems for treatment of viral infections. Thus, for example, acyclovir- and penciclovir-resistant strains of HSV-1 and HSV-2 are emerging, several HIV mutants have shown resistance to reverse transcriptase inhibitors, and there are constant mutations in influenza viruses. In addition, emerging viral infectious diseases, such as severe acute respiratory syndrome (SARS), Chikungunya virus, West Nile virus, and Zika virus, are presenting new challenges. Natural products have been and will continue to be excellent sources of medicinal agents. This Special Issue is directed at natural products drug discovery of antiviral agents. We welcome contributions directed at in-vitro and in-vivo screening of extracts and natural products against viruses, as well as in-silico efforts at antiviral drug discovery. Both original research papers and timely reviews are welcome.

Prof. Dr. William N. Setzer
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • Drug discovery
  • Antiviral agents
  • In-vitro screening
  • In-vivo screening
  • In-silico screening
  • Antiviral drug targets
  • Emerging viral diseases

Published Papers (6 papers)

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Research

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13 pages, 2193 KiB  
Article
Doratoxylon apetalum, an Indigenous Medicinal Plant from Mascarene Islands, Is a Potent Inhibitor of Zika and Dengue Virus Infection in Human Cells
by Juliano G. Haddad, Andrea Cristine Koishi, Arnaud Gaudry, Claudia Nunes Duarte dos Santos, Wildriss Viranaicken, Philippe Desprès and Chaker El Kalamouni
Int. J. Mol. Sci. 2019, 20(10), 2382; https://doi.org/10.3390/ijms20102382 - 14 May 2019
Cited by 24 | Viewed by 4109 | Correction
Abstract
Zika virus (ZIKV) and Dengue virus (DENV) are mosquito-borne viruses of the Flavivirus genus that could cause congenital microcephaly and hemorrhage, respectively, in humans, and thus present a risk to global public health. A preventive vaccine against ZIKV remains unavailable, and no specific [...] Read more.
Zika virus (ZIKV) and Dengue virus (DENV) are mosquito-borne viruses of the Flavivirus genus that could cause congenital microcephaly and hemorrhage, respectively, in humans, and thus present a risk to global public health. A preventive vaccine against ZIKV remains unavailable, and no specific antiviral drugs against ZIKV and DENV are licensed. Medicinal plants may be a source of natural antiviral drugs which mostly target viral entry. In this study, we evaluate the antiviral activity of Doratoxylum apetalum, an indigenous medicinal plant from the Mascarene Islands, against ZIKV and DENV infection. Our data indicated that D. apetalum exhibited potent antiviral activity against a contemporary epidemic strain of ZIKV and clinical isolates of four DENV serotypes at non-cytotoxic concentrations in human cells. Time-of-drug-addition assays revealed that D. apetalum extract acts on ZIKV entry by preventing the internalisation of virus particles into the host cells. Our data suggest that D. apetalum-mediated ZIKV inhibition relates to virus particle inactivation. We suggest that D. apetalum could be a promising natural source for the development of potential antivirals against medically important flaviviruses. Full article
(This article belongs to the Special Issue Natural Products against Viral Infections)
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16 pages, 1814 KiB  
Article
The Polyphenol-Rich Extract from Psiloxylon mauritianum, an Endemic Medicinal Plant from Reunion Island, Inhibits the Early Stages of Dengue and Zika Virus Infection
by Elodie Clain, Juliano G. Haddad, Andrea C. Koishi, Laura Sinigaglia, Walid Rachidi, Philippe Desprès, Claudia N. Duarte dos Santos, Pascale Guiraud, Nolwenn Jouvenet and Chaker El Kalamouni
Int. J. Mol. Sci. 2019, 20(8), 1860; https://doi.org/10.3390/ijms20081860 - 15 Apr 2019
Cited by 38 | Viewed by 4291
Abstract
The recent emergence and re-emergence of viral infections transmitted by vectors, such as the Zika virus (ZIKV) and Dengue virus (DENV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas of the [...] Read more.
The recent emergence and re-emergence of viral infections transmitted by vectors, such as the Zika virus (ZIKV) and Dengue virus (DENV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas of the world. Despite the high morbidity and mortality associated with these viral infections, antiviral therapies are missing. Medicinal plants have been widely used to treat various infectious diseases since millenaries. Several compounds extracted from plants exhibit potent effects against viruses in vitro, calling for further investigations regarding their efficacy as antiviral drugs. Here, we demonstrate that an extract from Psiloxylon mauritianum, an endemic medicinal plant from Reunion Island, inhibits the infection of ZIKV in vitro without exhibiting cytotoxic effects. The extract was active against different ZIKV African and Asian strains, including an epidemic one. Time-of-drug-addition assays revealed that the P. mauritianum extract interfered with the attachment of the viral particles to the host cells. Importantly, the P. mauritianum extract was also able to prevent the infection of human cells by four dengue virus serotypes. Due to its potency and ability to target ZIKV and DENV particles, P. mauritianum may be of value for identifying and characterizing antiviral compounds to fight medically-important flaviviruses. Full article
(This article belongs to the Special Issue Natural Products against Viral Infections)
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23 pages, 7131 KiB  
Article
Adenosine Induces EBV Lytic Reactivation through ADORA1 in EBV-Associated Gastric Carcinoma
by Su Jin Choi, Eunhyun Ryu, Seulki Lee, Sora Huh, Yu Su Shin, Byung Woog Kang, Jong Gwang Kim, Hyosun Cho and Hyojeung Kang
Int. J. Mol. Sci. 2019, 20(6), 1286; https://doi.org/10.3390/ijms20061286 - 14 Mar 2019
Cited by 11 | Viewed by 4466
Abstract
Cordyceps species are known to contain numerous bioactive compounds, including cordycepin. Extracts of Cordyceps militaris (CME) are used in diverse medicinal purposes because of their bioactive components. Cordycepin, one of the active components of CME, exhibits anti-proliferative, pro-apoptotic, and anti-inflammatory effects. Cordycepin structurally [...] Read more.
Cordyceps species are known to contain numerous bioactive compounds, including cordycepin. Extracts of Cordyceps militaris (CME) are used in diverse medicinal purposes because of their bioactive components. Cordycepin, one of the active components of CME, exhibits anti-proliferative, pro-apoptotic, and anti-inflammatory effects. Cordycepin structurally differs from adenosine in that its ribose lacks an oxygen atom at the 3′ position. We previously reported that cordycepin suppresses Epstein–Barr virus (EBV) gene expression and lytic replication in EBV-associated gastric carcinoma (EBVaGC). However, other studies reported that cordycepin induces EBV gene expression and lytic reactivation. Thus, it was reasonable to clarify the bioactive effects of CME bioactive compounds on the EBV life cycle. We first confirmed that CME preferentially induces EBV gene expression and lytic reactivation; second, we determined that adenosine in CME induces EBV gene expression and lytic reactivation; third, we discovered that the adenosine A1 receptor (ADORA1) is required for adenosine to initiate signaling for upregulating BZLF1, which encodes for a key EBV regulator (Zta) of the EBV lytic cycle; finally, we showed that BZLF1 upregulation by adenosine leads to delayed tumor development in the EBVaGC xenograft mouse model. Taken together, these results suggest that adenosine is an EBV lytic cycle inducer that inhibits EBVaGC development. Full article
(This article belongs to the Special Issue Natural Products against Viral Infections)
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Review

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23 pages, 956 KiB  
Review
Traditional Chinese Medicine as a Potential Source for HSV-1 Therapy by Acting on Virus or the Susceptibility of Host
by Wen Li, Xiao-Hua Wang, Zhuo Luo, Li-Fang Liu, Chang Yan, Chang-Yu Yan, Guo-Dong Chen, Hao Gao, Wen-Jun Duan, Hiroshi Kurihara, Yi-Fang Li and Rong-Rong He
Int. J. Mol. Sci. 2018, 19(10), 3266; https://doi.org/10.3390/ijms19103266 - 20 Oct 2018
Cited by 38 | Viewed by 8995
Abstract
Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60–95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune [...] Read more.
Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60–95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described. Full article
(This article belongs to the Special Issue Natural Products against Viral Infections)
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60 pages, 798 KiB  
Review
Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus
by Bahare Salehi, Nanjangud V. Anil Kumar, Bilge Şener, Mehdi Sharifi-Rad, Mehtap Kılıç, Gail B. Mahady, Sanja Vlaisavljevic, Marcello Iriti, Farzad Kobarfard, William N. Setzer, Seyed Abdulmajid Ayatollahi, Athar Ata and Javad Sharifi-Rad
Int. J. Mol. Sci. 2018, 19(5), 1459; https://doi.org/10.3390/ijms19051459 - 14 May 2018
Cited by 111 | Viewed by 15213
Abstract
Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to [...] Read more.
Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo. Full article
(This article belongs to the Special Issue Natural Products against Viral Infections)

Other

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1 pages, 185 KiB  
Correction
Correction: Haddad, J.G., et al. Doratoxylon apetalum, an Indigenous Medicinal Plant from Mascarene Islands, Is a Potent Inhibitor of Zika and Dengue Virus Infection in Human Cells Int. J. Mol. Sci. 2019, 20, 2382
by Juliano G. Haddad, Andrea Cristine Koishi, Arnaud Gaudry, Claudia Nunes Duarte dos Santos, Wildriss Viranaicken, Philippe Desprès and Chaker El Kalamouni
Int. J. Mol. Sci. 2020, 21(21), 7816; https://doi.org/10.3390/ijms21217816 - 22 Oct 2020
Viewed by 1416
Abstract
The author wishes to make the following correction to this paper [...] Full article
(This article belongs to the Special Issue Natural Products against Viral Infections)
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