scholarly journals Possible Antiviral Activity of 5-Aminolevulinic Acid in Feline Infectious Peritonitis Virus (Feline Coronavirus) Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Tomomi Takano ◽  
Kumi Satoh ◽  
Tomoyoshi Doki
Keyword(s):  
Antiviral Activity ◽  
Aminolevulinic Acid ◽  
Low Molecular Weight ◽  
Animal Cells ◽  
Feline Infectious Peritonitis ◽  
Treatment And Prevention ◽  
Amino Levulinic Acid ◽  
Life Threatening ◽  
Coronavirus Infection ◽  
Feline Coronavirus

Feline infectious peritonitis (FIP) is a life-threatening infectious disease of cats caused by virulent feline coronavirus (FIP virus: FIPV). For the treatment of FIP, several effective antivirals were recently reported, but many of these are not available for practical use. 5-amino levulinic acid (5-ALA) is a low-molecular-weight amino acid synthesized in plant and animal cells. 5-ALA can be synthesized in a large amount, and it is widely applied in the medical and agricultural fields. We hypothesized that 5-ALA inhibits FIPV infection. Therefore, we evaluated its antiviral activity against FIPV in felis catus whole fetus-4 cells and feline primary macrophages. FIPV infection was significantly inhibited by 250 μM 5-ALA. Our study suggested that 5-ALA is applicable for the treatment and prevention of FIPV infection.

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 Antiviral Effects of Hydroxychloroquine and Type I Interferon on In Vitro Fatal Feline Coronavirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 576 ◽  
Author(s):  
Tomomi Takano ◽  
Kumi Satoh ◽  
Tomoyoshi Doki ◽  
Taishi Tanabe ◽  
Tsutomu Hohdatsu
Keyword(s):  
Viral Infections ◽  
Viral Disease ◽  
High Morbidity ◽  
Type I ◽  
Feline Infectious Peritonitis ◽  
Antiviral Effects ◽  
Immune Mediated ◽  
Coronavirus Infection ◽  
Feline Coronavirus

Feline infectious peritonitis (FIP) is a viral disease with a high morbidity and mortality by the FIP virus (FIPV, virulent feline coronavirus). Several antiviral drugs for FIP have been identified, but many of these are expensive and not available in veterinary medicine. Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed. We investigated whether HCQ in association with interferon-ω (IFN-ω) is effective for FIPV in vitro. A total of 100 μM of HCQ significantly inhibited the replication of types I and II FIPV. Interestingly, the combination of 100 μM of HCQ and 104 U/mL of recombinant feline IFN-ω (rfIFN-ω, veterinary registered drug) increased its antiviral activity against type I FIPV infection. Our study suggested that HCQ and rfIFN-ω are applicable for treatment of FIP. Further clinical studies are needed to verify the combination of HCQ and rIFN-ω will be effective and safe treatment for cats with FIP.

scholarly journals Feline coronavirus infection

2021 ◽  
Vol 273 ◽  
pp. 02025
Author(s):  
Aleksey Ermakov ◽  
Tatyana Lipilkina ◽  
Pavel Lipilkin ◽  
Igor Popov
Keyword(s):  
Primary Prevention ◽  
Therapeutic Interventions ◽  
Feline Infectious Peritonitis ◽  
Clinical Diagnostic ◽  
Coronavirus Infection ◽  
Near Future ◽  
Feline Coronavirus ◽  
Prevention And Therapy

The main feature of feline coronavirus infection is its manifestation in the form of peritonitis. Feline infectious peritonitis is a highly lethal disease that lacks primary prevention and therapy. Therefore, feline infectious peritonitis is an epizootic problem in the near future. In our review, we demonstrate the current clinical, diagnostic, and therapeutic interventions for feline infectious peritonitis, as well as hypotheses of origin.

scholarly journals Feline Coronavirus infections and feline infectious peritonitis

2018 ◽  
Vol 50 (3) ◽  
pp. 199
Author(s):  
A. TZIVARA (Α. ΤΖΙΒΑΡΑ) ◽  
S. K. KRITAS (Σ.Κ. ΚΡΗΤΑΣ)
Keyword(s):  
Gastrointestinal Disease ◽  
Clinical Signs ◽  
Asymptomatic Infection ◽  
Temperature Sensitive ◽  
Feline Infectious Peritonitis ◽  
Antibody Titers ◽  
Coronavirus Infection ◽  
Different Strains ◽  
Physical Findings ◽  
Feline Coronavirus

Cats are susceptible to infection with several different strains of feline Coronavirus. Depending on the involved strain, clinical signs may range from asymptomatic infection to gastrointestinal disease or fibrinous serositis and disseminated vasculitis, commonly known as feline infectious peritonitis (FIP). Excretion of virus by infected cats into the environment occurs by faeces, oronasal secretions and urine. The feline coronaviruses are rapidly inactivated by most disinfectants. Clinical diagnosis of Coronavirus infection is made by evaluating the case history, physical findings, laboratory results, Coronavirus antibody titers and tissue biopsy. A temperature-sensitive feline infectious peritonitis virus vaccine has become available for healthy 16 week of age or older cats.

scholarly journals Antiviral activity of itraconazole against type I feline coronavirus infection

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Tomomi Takano ◽  
Misuzu Akiyama ◽  
Tomoyoshi Doki ◽  
Tsutomu Hohdatsu
Keyword(s):  
Antiviral Activity ◽  
Type I ◽  
Coronavirus Infection ◽  
Feline Coronavirus

scholarly journals Development of Feline Ileum- and Colon-Derived Organoids and Their Potential Use to Support Feline Coronavirus Infection

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2085 ◽  
Author(s):  
Gergely Tekes ◽  
Rosina Ehmann ◽  
Steeve Boulant ◽  
Megan L. Stanifer
Keyword(s):  
Cell Culture ◽  
Molecular Mechanisms ◽  
Domestic Cat ◽  
Contributing Factors ◽  
Feline Infectious Peritonitis ◽  
Culture Models ◽  
Coronavirus Infection ◽  
Cell Culture Models ◽  
Feline Coronavirus ◽  
Potential Use

Feline coronaviruses (FCoVs) infect both wild and domestic cat populations world-wide. FCoVs present as two main biotypes: the mild feline enteric coronavirus (FECV) and the fatal feline infectious peritonitis virus (FIPV). FIPV develops through mutations from FECV during a persistence infection. So far, the molecular mechanism of FECV-persistence and contributing factors for FIPV development may not be studied, since field FECV isolates do not grow in available cell culture models. In this work, we aimed at establishing feline ileum and colon organoids that allow the propagation of field FECVs. We have determined the best methods to isolate, culture and passage feline ileum and colon organoids. Importantly, we have demonstrated using GFP-expressing recombinant field FECV that colon organoids are able to support infection of FECV, which were unable to infect traditional feline cell culture models. These organoids in combination with recombinant FECVs can now open the door to unravel the molecular mechanisms by which FECV can persist in the gut for a longer period of time and how transition to FIPV is achieved.

scholarly journals Phytoalexins: Sources and Their Pharmacological Potential

2020 ◽  
Vol 8 (1) ◽  
pp. 1-8
Author(s):  
Rakesh K Sindhu ◽  
Bhavika Arora ◽  
Sandeep Arora
Keyword(s):  
Diabetes Mellitus ◽  
Heart Attack ◽  
Web Of Science ◽  
Therapeutic Potential ◽  
Low Molecular Weight ◽  
Treatment And Prevention ◽  
Microbial Infections ◽  
Life Threatening ◽  
Health And Disease ◽  
Pharmacological Potential

Background: Plants are easily prone towards microbial infections on exposure to microorganisms and pathogens. In order to defense, plants produce low molecular weight secondary metabolites which were later known as “Phytoalexins”. These molecules have vast therapeutic potential also. Purpose: The purpose of this review is to explore the phytoalexins and their pharmacological effects.Methods: The data included from the articles were published from Web of Science, PubMed, Medline, Scopus, and Embase by using relevant keywords including plants possessing phytoalexins and their specific biological applications.Results: The review insights the potential of phytoalexins in various diseases and to explore have phytoalexins applications in human health and disease control. Conclusions: On the basis of this review we may be conclude that phytoalexins have tremendous potential in the treatment and prevention of various life-threatening diseases like diabetes mellitus, cancer, brain damage, and heart attack.

scholarly journals The Effect of Natural Feline Coronavirus Infection on the Host Immune Response: A Whole-Transcriptome Analysis of the Mesenteric Lymph Nodes in Cats with and without Feline Infectious Peritonitis

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 524
Author(s):  
Alexandra J. Malbon ◽  
Giancarlo Russo ◽  
Carole Burgener ◽  
Emi N. Barker ◽  
Marina L. Meli ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Mesenteric Lymph Nodes ◽  
Feline Infectious Peritonitis ◽  
Mesenteric Lymph ◽  
Immune Balance ◽  
Differential Gene ◽  
Coronavirus Infection ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
Feline Coronavirus

Feline infectious peritonitis (FIP) is a coronavirus-induced disease of cats, in which the immune system is known to play a crucial, but complex, role in the pathogenesis. This role is still incompletely understood, with involvement of both host and viral factors. To evaluate differential gene expression and pathway involvement in feline coronavirus (FCoV) infection and FIP, we applied next-generation RNA-sequencing of the mesenteric lymph nodes from cats with naturally-acquired FIP, as well as those with systemic FCoV infection without FIP, and those with neither. Viral infection was associated with upregulation of viral defenses regardless of the disease state, but to a greater degree in FIP. FIP was associated with higher pro-inflammatory pathway enrichment, whilst non-FIP FCoV-positive cats showed lower enrichment of humoral immunity pathways, below that of uninfected cats in the case of immunoglobulin production pathways. This host response is presumed to be protective. In FIP, downregulation of T cell-related processes was observed, which did not occur in non-FIP FCoV-positive cats. These results emphasize the importance of the host’s immune balance in determining the outcome of the FCoV infection.

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.

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