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Journal ArticleDOI

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction.

01 May 2007-Antiviral Research (Elsevier)-Vol. 74, Iss: 2, pp 92-101
TL;DR: Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner and suggested that emodin may be considered as a potential lead therapeutic agent in the treatment of SARS.
About: This article is published in Antiviral Research.The article was published on 2007-05-01 and is currently open access. It has received 354 citations till now. The article focuses on the topics: Emodin & Rheum officinale.
Citations
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Journal ArticleDOI
TL;DR: This study presents an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network.
Abstract: Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV–host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.

1,226 citations

Journal ArticleDOI
TL;DR: It is suggested that all the potential interventions be implemented to control the emerging COVID‐19 if the infection is uncontrollable and the current children's RNA‐virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers.
Abstract: An outbreak of a novel coronavirus (COVID-19 or 2019-CoV) infection has posed significant threats to international health and the economy. In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of disease. Here, we have conducted an online search for all treatment options related to coronavirus infections as well as some RNA-virus infection and we have found that general treatments, coronavirus-specific treatments, and antiviral treatments should be useful in fighting COVID-19. We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children's RNA-virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, convalescent plasma should be given to COVID-19 patients if it is available. In conclusion, we suggest that all the potential interventions be implemented to control the emerging COVID-19 if the infection is uncontrollable.

1,009 citations


Cites background from "Emodin blocks the SARS coronavirus ..."

  • ...The mAb could efficiently neutralize SARS‐CoV and inhibit syncytia formation between cells expressing the S protein and those expressing the SARS‐CoV receptor ACE2....

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  • ...These findings suggested that emodin and promazine might be able to in- hibit SARS‐CoV infectivity through blocking the interaction of S protein and ACE2....

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  • ...Emodin is an anthraquinone compound derived from genus Rheum and Polygonum and it is also a virucidal agent.92 Emodin could sig- nificantly block the interaction between the S protein of SARS‐CoV and ACE2....

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  • ...Therefore, emodin might abolish SARS‐CoV infection by competing for the binding site of S protein with ACE2.(93)...

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  • ...Therefore, emodin might abolish SARS‐CoV infection by competing for the binding site of S protein with ACE2....

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Journal ArticleDOI
TL;DR: The interaction between the viral spike protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.
Abstract: Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.

927 citations

Journal ArticleDOI
TL;DR: An overview of the known clinical features and treatment options for COVID‐19 is provided and quarantine is the only intervention that appears to be effective in decreasing the contagion rate.
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a novel coronavirus from the same family as SARS-CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), presents flu-like symptoms which can become serious in high-risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID-19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: 'COVID-19', '2019-nCoV', 'coronavirus' and 'SARS-CoV-2'. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID-19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real-time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow-up. To date, there is no evidence of any effective treatment for COVID-19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence-based treatment modality.

900 citations

Journal ArticleDOI
Yang Yang1, Shahidul Islam1, Jin Wang1, Yuan Li1, Xin Chen1 
TL;DR: Clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed and experiment studies that provide an insight into the mechanism underlying the therapeutic effect ofTCM are introduced.
Abstract: Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.

638 citations

References
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Journal ArticleDOI
27 Nov 2003-Nature
TL;DR: It is found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells, indicating that ACE2 is a functional receptor for SARS-CoV.
Abstract: Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells Together our data indicate that ACE2 is a functional receptor for SARS-CoV

5,149 citations

Journal ArticleDOI
TL;DR: The novel coronavirus might have a role in causing SARS and was detected in a variety of clinical specimens from patients with SARS but not in controls.
Abstract: BACKGROUND: The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. METHODS: Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. RESULTS: A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. CONCLUSIONS: The novel coronavirus might have a role in causing SARS.

4,180 citations

Journal ArticleDOI
TL;DR: A novel coronavirus is associated with this outbreak of severe acute respiratory syndrome, and the evidence indicates that this virus has an etiologic role in SARS.
Abstract: background A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. methods We received clinical specimens from patients in six countries and tested them, using virus isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. results No classic respiratory or bacterial respiratory pathogen was consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted microscopically in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination of cultures revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription–polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point source outbreak. Indirect fluorescent antibody tests and enzyme-linked immunosorbent assays made with the new coronavirus isolate have been used to demonstrate a virus-specific serologic response. Preliminary studies suggest that this virus may never before have infected the U.S. population. conclusions A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. The name Urbani SARS-associated coronavirus is proposed for the virus.

4,065 citations

Journal ArticleDOI
TL;DR: Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

2,753 citations

Journal ArticleDOI
30 May 2003-Science
TL;DR: Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closelyrelated to any of the previouslycharacterized coronaviruses.
Abstract: In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.

2,420 citations

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