scholarly journals Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Sophie Le Poder
Keyword(s):  
Infectious Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Host Cell ◽  
Companion Animals ◽  
Cell Tropism ◽  
Human Coronavirus ◽  
Feline Infectious Peritonitis ◽  
Canine Coronavirus ◽  
Coronavirus Infection ◽  
Systemic Infections

A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.

scholarly journals Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Wayne Vuong ◽  
Muhammad Bashir Khan ◽  
Conrad Fischer ◽  
Elena Arutyunova ◽  
Tess Lamer ◽  
...  
Keyword(s):  
Drug Target ◽  
Covalent Modification ◽  
Human Coronavirus ◽  
Feline Infectious Peritonitis ◽  
Drug Candidates ◽  
Main Protease ◽  
Coronavirus Infection ◽  
Reversible Formation ◽  
Nanomolar Range ◽  
Feline Coronavirus

Abstract The main protease, Mpro (or 3CLpro) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the Mpro from both SARS-CoV and SARS-CoV-2 with IC50 values in the nanomolar range. Crystal structures of SARS-CoV-2 Mpro with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals. The work here lays the framework for their use in human trials for the treatment of COVID-19.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Megan M. Angelini ◽  
Marzieh Akhlaghpour ◽  
Benjamin W. Neuman ◽  
Michael J. Buchmeier
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Host Cell ◽  
Rna Viruses ◽  
Membrane Vesicles ◽  
Full Length ◽  
Nonstructural Proteins ◽  
Human Coronavirus ◽  
Double Membrane ◽  
Infected Cells ◽  
Proliferation Ability

ABSTRACTCoronaviruses (CoV), like other positive-stranded RNA viruses, redirect and rearrange host cell membranes for use as part of the viral genome replication and transcription machinery. Specifically, coronaviruses induce the formation of double-membrane vesicles in infected cells. Although these double-membrane vesicles have been well characterized, the mechanism behind their formation remains unclear, including which viral proteins are responsible. Here, we use transfection of plasmid constructs encoding full-length versions of the three transmembrane-containing nonstructural proteins (nsps) of the severe acute respiratory syndrome (SARS) coronavirus to examine the ability of each to induce double-membrane vesicles in tissue culture. nsp3 has membrane disordering and proliferation ability, both in its full-length form and in a C-terminal-truncated form. nsp3 and nsp4 working together have the ability to pair membranes. nsp6 has membrane proliferation ability as well, inducing perinuclear vesicles localized around the microtubule organizing center. Together, nsp3, nsp4, and nsp6 have the ability to induce double-membrane vesicles that are similar to those observed in SARS coronavirus-infected cells. This activity appears to require the full-length form of nsp3 for action, as double-membrane vesicles were not seen in cells coexpressing the C-terminal truncation nsp3 with nsp4 and nsp6.IMPORTANCEAlthough the majority of infections caused by coronaviruses in humans are relatively mild, the SARS outbreak of 2002 to 2003 and the emergence of the human coronavirus Middle Eastern respiratory syndrome (MERS-CoV) in 2012 highlight the ability of these viruses to cause severe pathology and fatality. Insight into the molecular biology of how coronaviruses take over the host cell is critical for a full understanding of any known and possible future outbreaks caused by these viruses. Additionally, since membrane rearrangement is a tactic used by all known positive-sense single-stranded RNA viruses, this work adds to that body of knowledge and may prove beneficial in the development of future therapies not only for human coronavirus infections but for other pathogens as well.

Search for targeted anticmoid drug remdesivir: Hope for success and first failures

2020 ◽  
pp. 22-24
Author(s):  
A. Nikitina
Keyword(s):  
Infectious Disease ◽  
Severe Acute Respiratory Syndrome ◽  
Coronavirus Infection

Coronavirus infection 2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome 2 Coronovirus (SARS-CoV-2). In the article, we provide an overview of some works that address the measures and precautions regarding COVID-19, describe the results of a study of the treatment of COVID-19 using the drug remdesivir, the prospects for further studies, the use of the drug remdesivir in the treatment of COVID-19.

scholarly journals A Prospective Hospital‐Based Study of the Clinical Impact of Non–Severe Acute Respiratory Syndrome (Non‐SARS)–Related Human Coronavirus Infection

2006 ◽  
Vol 43 (8) ◽  
pp. 1009-1015 ◽  
Author(s):  
Jorge Garbino ◽  
Sophie Crespo ◽  
J.‐D. Aubert ◽  
Thierry Rochat ◽  
Beatrice Ninet ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Impact ◽  
Human Coronavirus ◽  
Coronavirus Infection

scholarly journals Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives

2020 ◽  
Vol 11 ◽  
Author(s):  
Cheng-Wei Yang ◽  
Yue-Zhi Lee ◽  
Hsing-Yu Hsu ◽  
Jia-Tsrong Jan ◽  
Yi-Ling Lin ◽  
...  
Keyword(s):  
Host Cell ◽  
Broad Spectrum ◽  
Human Coronavirus ◽  
Feline Infectious Peritonitis ◽  
Therapeutic Development ◽  
Host Cell Factors ◽  
Transmissible Gastroenteritis ◽  
Human Coronaviruses ◽  
Compare And Contrast ◽  
Transmissible Gastroenteritis Coronavirus

Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively. We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development. Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC50 values of up to 8 and 16 nM, respectively. Strikingly, the tylophorine-based compounds tested inhibited viral yields of HCoV-OC43 to a much greater extent (7–8 log magnitudes of p.f.u./ml) than the cardiotonic steroids (about 2–3 log magnitudes of p.f.u./ml), as determined by end point assays. Based on these results, three tylophorine-based compounds were further examined for their anti-viral activities on two other human coronaviruses, HCoV-229E and SARS-CoV-2. These three tylophorine-based compounds inhibited HCoV-229E with EC50 values of up to 6.5 nM, inhibited viral yields of HCoV-229E by 6–7 log magnitudes of p.f.u./ml, and were also found to inhibit SARS-CoV-2 with EC50 values of up to 2.5–14 nM. In conclusion, tylophorine-based compounds are potent, broad-spectrum inhibitors of coronaviruses including SARS-CoV-2, and could be used for the treatment of COVID-19.

scholarly journals Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication

2020 ◽  
Author(s):  
Wayne Vuong ◽  
Muhammad Bashir Khan ◽  
Conrad Fischer ◽  
Elena Arutyunova ◽  
Tess Lamer ◽  
...  
Keyword(s):  
Drug Target ◽  
Covalent Modification ◽  
Human Coronavirus ◽  
Feline Infectious Peritonitis ◽  
Drug Candidates ◽  
Main Protease ◽  
Coronavirus Infection ◽  
Reversible Formation ◽  
Nanomolar Range ◽  
Feline Coronavirus

AbstractThe COVID-19 pandemic, attributed to the SARS-CoV-2 coronavirus infection, resulted in millions infected worldwide and an immediate need for antiviral treatments. The main protease (Mpro) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide and subsequent viral replication. Feline infectious peritonitis, a fatal infection in cats caused by a coronavirus, was successfully treated previously with a dipeptide-based protease inhibitor. Here we show this drug, GC376, and its analog GC373, are effective inhibitors of the Mpro from both SARS-CoV and SARS-CoV-2 with IC50 values in the nanomolar range. Crystal structures of the SARS-CoV and SARS-CoV-2 Mpro with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 in cell culture, with EC50 values near one micromolar and little to no toxicity. These protease inhibitors are soluble, non-toxic, and bind reversibly. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals (cats). The work here lays the framework for their use in human trials for the treatment of COVID-19.

scholarly journals Epilepsy Management during the COVID-19 Pandemic in Epilepsy Monitoring Unit

2020 ◽  
Vol 3 (S4) ◽  
pp. 22-24
Author(s):  
Izadi Laybidi Maryam ◽  
Keyword(s):  
Infectious Disease ◽  
Severe Acute Respiratory Syndrome ◽  
The Novel ◽  
Human Coronavirus ◽  
Epilepsy Monitoring

Coronavirus disease 2019 (COVID-19) is a rapidly spreading infectious disease caused by the novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

scholarly journals Coronaviruses induce the expression of the dual specificity phosphatase DUSP1/MKP1.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Host Cell ◽  
Microarray Data ◽  
The United States ◽  
Human Coronavirus ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Coronavirus Infection ◽  
Human Coronavirus 229E ◽  
Level Analysis

Coronavirus infection is an emerging public health threat in the United States and worldwide (1). We mined published microarray data to perform systems-level analysis of host cell transcription following infection with multiple coronavirus types in order to identify therapeutic targets and host cell vulnerabilities (2, 3). We identified the dual specificity phosphatase DUSP1 (also known as MKP1) as differentially expressed in vitro following infection with human coronavirus 229E, HCoV-229E and with Middle East Respiratory Syndrome coronavirus, MERS-CoV. DUSP1 expression significantly increases after coronavirus infection in vitro. DUSP1 may be of relevance to the pathology of coronavirus infection.

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