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      Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry

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          Abstract

          Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.

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          Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL pro inhibition

          Young Bae Ryu, Hyung Jeong, Jang Hoon Kim … (2010)
          Graphical abstract Inhibitory activity appeared to be associated with the presence of an apigenin moiety at position C-3′ of flavones, as biflavonoid had an effect on SARS-CoV 3CLpro inhibitory activity.
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            Scavenger receptor B2 is a cellular receptor for enterovirus 71.

            Seiya Yamayoshi, Yasuko Yamashita, Jifen Li … (2009)
            Enterovirus 71 (EV71) belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae. EV71, together with coxsackievirus A16 (CVA16), are most frequently associated with hand, foot and mouth disease (HFMD). Although HFMD is considered a mild exanthematous infection, infections involving EV71, but not CVA16, can progress to severe neurological disease, including fatal encephalitis, aseptic meningitis and acute flaccid paralysis. In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in Taiwan, Malaysia, Singapore, Japan and China. Here, we show that human scavenger receptor class B, member 2 (SCARB2, also known as lysosomal integral membrane protein II or CD36b like-2) is a receptor for EV71. EV71 binds soluble SCARB2 or cells expressing SCARB2, and the binding is inhibited by an antibody to SCARB2. Expression of human SCARB2 enables normally unsusceptible cell lines to support EV71 propagation and develop cytopathic effects. EV71 infection is hampered by the antibody to SCARB2 and soluble SCARB2. SCARB2 also supports the infection of the milder pathogen CVA16. The identification of SCARB2 as an EV71 and CVA16 receptor contributes to a better understanding of the pathogenicity of these viruses.
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              Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71.

              Yorihiro Nishimura, Masayuki Shimojima, Yoshio Tano … (2009)
              Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), a common febrile disease occurring mainly in young children. Although clinical manifestations of HFMD are usually mild and self limiting, a severe EV71 outbreak can lead to a diverse array of neurological diseases. Identification of the specific cellular receptors is crucial for elucidating the mechanism of early virus-host interactions and the pathogenesis of enteroviruses. Here we identify human P-selectin glycoprotein ligand-1 (PSGL-1; CD162), a sialomucin membrane protein expressed on leukocytes that has a major role in early stages of inflammation, as a functional receptor for EV71 using an expression cloning method by panning. The N-terminal region of PSGL-1 binds specifically to EV71. Stable PSGL-1 expression allowed EV71 entry and replication, and development of cytopathic effects in nonsusceptible mouse L929 cells. Five out of eight EV71 strains bound soluble PSGL-1 and used intact PSGL-1 as the primary receptor for infection of Jurkat T cells. Three other EV71 strains did not use PSGL-1, suggesting the presence of strain-specific replication of EV71 in leukocytes. EV71 replicated in nonleukocyte cell lines in a PSGL-1-independent manner, indicating the presence of alternative receptor(s) for EV71. The identification of PSGL-1 as a receptor for EV71 sheds new light on a role for PSGL-1-positive leukocytes in cell tropism and pathogenesis during the course of HFMD and other EV71-mediated diseases.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Viruses
                Journal ID (iso-abbrev): Viruses
                Journal ID (publisher-id): viruses
                Title: Viruses
                Publisher: MDPI
                ISSN (Electronic): 1999-4915
                Publication date (Electronic): 11 April 2012
                Publication date Collection: April 2012
                Volume: 4
                Issue: 4
                Pages: 539-556
                Affiliations
                [1 ]Department of Biochemistry, Chang Gung University, Kweishan, Taoyuan 333, Taiwan; Email: anny910111@ 123456hotmail.com
                [2 ]Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan 333, Taiwan; Email: ylleu@ 123456mail.cgu.edu.tw
                [3 ]Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan
                [4 ]Research Center for Emerging Viral Infections, Chang Gung University, Kweishan, Taoyuan 333, Taiwan
                Author notes
                [† ]

                These authors contributed equally to this work.

                [* ] Author to whom correspondence should be addresses; Email: jimtong@ 123456mail.cgu.edu.tw ; Tel.:+886-3-2118407; Fax: +886-3-3-2118407.
                Article
                Publisher ID: viruses-04-00539
                DOI: 10.3390/v4040539
                PMC ID: 3347322
                PubMed ID: 22590685
                SO-VID: 6fe9e6c4-67d4-4c32-83b6-18da18e7fdbf
                Copyright © © 2012 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 07 March 2012
                Date revision received : 26 March 2012
                Date accepted : 03 April 2012
                Categories
                Subject: Article

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: attachment assay,enterovirus 71,penetration assay,cytopathic effect,daphne genkwa sieb. et zucc.,yuanhua
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: attachment assay, enterovirus 71, penetration assay, cytopathic effect, daphne genkwa sieb. et zucc., yuanhua

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