Emodin inhibits current through SARS-associated coronavirus 3a protein

Schwarz, Sebastian; Wang, Kai; Yu, Wei; Sun, Bing; Schwarz, Wolfgang

doi:10.1016/j.antiviral.2011.02.008

Cited by 170 publications

(160 citation statements)

References 21 publications

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“…The typical characteristic of ion channels is the selectivity for one type of ions [42] and this may involve in its viral life cycle regulation [43]. Considering the essential role of viroporins in the viral life cycle, channel inhibitors have become attractive drugs for an antiviral therapy [44][45][46][47][48]. Since the ORF4a channel showed the similar selectivity for monovalent cations to viroporins above, the inhibitors of these viroporins could have the capacity to block ORF4a channel, which should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production

Zhang

Wang

et al. 2014

Biochimica et Biophysica Acta (BBA) - Biomembranes

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In addition to a set of canonical genes, coronaviruses encode additional accessory proteins. A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Previously, we demonstrated that this locus, which contains the gene for accessory protein 3a from severe acute respiratory syndrome coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus release. In the current study, we explored whether the ORF4a protein of HCoV-229E has similar functions. Our findings revealed that the ORF4a proteins were expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment (ERGIC). The ORF4a proteins formed homo-oligomers through disulfide bridges and possessed ion channel activity in both Xenopus oocytes and yeast. Based on the measurement of conductance to different monovalent cations, the ORF4a was suggested to form a non-selective channel for monovalent cations, although Li(+) partially reduced the inward current. Furthermore, viral production decreased when the ORF4a protein expression was suppressed by siRNA in infected cells. Collectively, this evidence indicates that the HCoV-229E ORF4a protein is functionally analogous to the SARS-CoV 3a protein, which also acts as a viroporin that regulates virus production. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking.

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Section: Discussionmentioning

confidence: 99%

The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production

Zhang

Wang

et al. 2014

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…It is too soon to say whether all of the mutations relevant to the FECV-to-FIPV transition have been found. Although we do not fully understand how these mutations function in disease, they do suggest potential targets for antiviral drugs, such as protease inhibitors (Kim et al, 2013) or viral ion channel blockers (Schwarz et al, 2011).…”

Section: Mutations In the S Genementioning

confidence: 96%

“…bat coronavirus) forms (Tan et al, 2004). The most recent studies on the ORF 3a protein of SARS coronavirus indicate that it forms a cation-selective channel that is expressed in infected cells and is involved in release of virions (Schwarz et al, 2011). Is it also possible that mutations in FIPV ORF 3c protein inhibit apoptosis of infected macrophages?…”

Section: Mutations In the Orf 3c Accessory Genementioning

confidence: 99%

An update on feline infectious peritonitis: Virology and immunopathogenesis

Pedersen

2014

The Veterinary Journal

185

264

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Feline infectious peritonitis (FIP) continues to be one of the most researched infectious diseases of cats. The relatively high mortality of FIP, especially for younger cats from catteries and shelters, should be reason enough to stimulate such intense interest. However, it is the complexity of the disease and the grudging manner in which it yields its secrets that most fascinate researchers. Feline leukemia virus infection was conquered in less than two decades and the mysteries of feline immunodeficiency virus were largely unraveled in several years. After a half century, FIP remains one of the last important infections of cats for which we have no single diagnostic test, no vaccine and no definitive explanations for how virus and host interact to cause disease. How can a ubiquitous and largely non-pathogenic enteric coronavirus transform into a highly lethal pathogen? What are the interactions between host and virus that determine both disease form (wet or dry) and outcome (death or resistance)? Why is it so difficult, and perhaps impossible, to develop a vaccine for FIP? What role do genetics play in disease susceptibility? This review will explore research conducted over the last 5 years that attempts to answer these and other questions. Although much has been learned about FIP in the last 5 years, the ultimate answers remain for yet more studies.

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“…Moreover, the antiviral capacity of emodin against enveloped viruses is due to its affinity for phospholipid membrane and weakeness for hydrophobic interactions between hydrocarbon chains in phospholipid bilayers [13,19]. Emodin can also inhibit the 3a ion channel of coronavirus SARS-CoV and HCoV-OC43 as well as virus release from HCoV-OC43 with a K 1/2 value of about 20 μM [16]. And emodin may exert its antiviral activity by direct inhibiting UL12 alkaline nuclease activity of HSV-1 [14,28].…”

Section: Discussionmentioning

confidence: 99%

“…A number of pharmacological properties including anti-microbial, anti-inflammatory, antiviral, anticancer, immunosuppressive, and chemopreventive effects have been suggested [12,13]. Moreover, an increasing number of studies, including those from our laboratory, have extended the antiviral activity of emodin to many RNA and DNA viruses, enveloped and non-enveloped viruses, and pH-dependent and independent viruses, such as herpes simplex virus [14], hepatitis B virus [15], severe acute respiratory syndrome (SARS) coronavirus [16], etc. These findings are crucial for the understanding of the pharmacological properties of emodin, since despite extensive studies of its antiviral effects, the antiviral activity of emodin against CVB 4 virus infections is still incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B4

et al. 2013

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Abstract:The lack of effective therapeutics for Coxsackievirus B 4 (CVB 4 ) infection underscores the importance of finding novel antiviral compounds. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is one of the natural anthraquinone derivatives obtained from the root and rhizome of Polygonum cuspidatum. In the present study, the possibility of using emodin as a potential antiviral to treat CVB 4 infection was explored in vitro and in mice. Emodin reduced CVB 4 entry and replication on Hep-2 cells in a concentration-and time-dependent manner, with a 50% effective concentration (EC 50 ) of 12.06 μM and selectivity index (SI) of 5.08, respectively. The inhibitory effect of emodin for CVB 4 entry and replication was further confirmed by a quantitative real time PCR (qPCR) assay. The results further showed that the mice orally treated with different dosages of emodin displayed a dose dependent increase of survival rate, body weight and prolonged mean time of death (MTD), accompanied by significantly decreased myocardial virus titers and pathologic scores/lesions. Moreover, emodin could inhibit CVB 4 -induced apoptosis in vitro and in vivo. Our results indicated that emodin could be used as potential antiviral in the post-exposure prophylaxis for CVB 4 infection.

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Emodin inhibits current through SARS-associated coronavirus 3a protein

Cited by 170 publications

References 21 publications

The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production

The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production

An update on feline infectious peritonitis: Virology and immunopathogenesis

In Vitro and in Vivo Studies of the Inhibitory Effects of Emodin Isolated from Polygonum cuspidatum on Coxsakievirus B4

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