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Viruses Aug 2023Feline coronavirus (FCoV) is a ubiquitous RNA virus of cats, which is transmitted faeco-orally. In these guidelines, the European Advisory Board on Cat Diseases (ABCD)... (Review)
Review
Feline coronavirus (FCoV) is a ubiquitous RNA virus of cats, which is transmitted faeco-orally. In these guidelines, the European Advisory Board on Cat Diseases (ABCD) presents a comprehensive review of feline infectious peritonitis (FIP). FCoV is primarily an enteric virus and most infections do not cause clinical signs, or result in only enteritis, but a small proportion of FCoV-infected cats develop FIP. The pathology in FIP comprises a perivascular phlebitis that can affect any organ. Cats under two years old are most frequently affected by FIP. Most cats present with fever, anorexia, and weight loss; many have effusions, and some have ocular and/or neurological signs. Making a diagnosis is complex and ABCD FIP Diagnostic Approach Tools are available to aid veterinarians. Sampling an effusion, when present, for cytology, biochemistry, and FCoV RNA or FCoV antigen detection is very useful diagnostically. In the absence of an effusion, fine-needle aspirates from affected organs for cytology and FCoV RNA or FCoV antigen detection are helpful. Definitive diagnosis usually requires histopathology with FCoV antigen detection. Antiviral treatments now enable recovery in many cases from this previously fatal disease; nucleoside analogues (e.g., oral GS-441524) are very effective, although they are not available in all countries.
Topics: Cats; Animals; Feline Infectious Peritonitis; Body Fluids; Antigens, Viral; Antiviral Agents; Coronavirus, Feline
PubMed: 37766254
DOI: 10.3390/v15091847 -
Journal of Veterinary Internal Medicine 2023Feline infectious peritonitis (FIP) is a viral disease in cats, caused by certain strains of coronavirus and has a high case fatality rate. (Observational Study)
Observational Study
BACKGROUND
Feline infectious peritonitis (FIP) is a viral disease in cats, caused by certain strains of coronavirus and has a high case fatality rate.
OBJECTIVE
This case series reports the outcomes of treatment of cats with FIP using molnupiravir.
ANIMALS
Eighteen cats diagnosed with FIP at the You-Me Animal Clinic, Sakura-shi, Japan between January and August 2022, and whose owners gave informed consent to this experimental treatment.
METHODS
For this prospective observational study, molnupiravir tablets were compounded in-house at the You-Me Animal Clinic. Owners administered 10-20 mg/kg PO twice daily. Standard treatment duration was 84 days.
RESULTS
Among 18 cats, 13 cats had effusive FIP and 5 had noneffusive FIP. Three cats had neurological or ocular signs of FIP before treatment. Four cats, all with effusive FIP, died or were euthanized within 7 days of starting treatment. The remaining 14 cats completed treatment and remained in remission at the time of writing (139-206 days after starting treatment). Elevated serum alanine transaminase (ALT) activity was found in 3 cats, all at Days 7-9, and all recovered without management. Two cats with jaundice were hospitalized, 1 during treatment (Day 37) and 1 with severe anemia at the start of treatment.
CONCLUSIONS AND CLINICAL IMPORTANCE
This case series suggests that molnupiravir might be an effective and safe treatment for domestic cats with FIP at a dose of 10-20 mg/kg twice daily.
Topics: Cats; Animals; Feline Infectious Peritonitis; Coronavirus, Feline; Coronavirus Infections; Virus Diseases; Cat Diseases
PubMed: 37551843
DOI: 10.1111/jvim.16832 -
MBio Feb 2024Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes severe diarrhea in neonatal piglets, which is associated with a high mortality rate....
Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes severe diarrhea in neonatal piglets, which is associated with a high mortality rate. Thus, developing effective and safe vaccines remains a top priority for controlling PEDV infection. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines encoding either the full-length PEDV spike (S) protein or a multiepitope chimeric spike (Sm) protein. We found that the S mRNA-LNP vaccine was superior to the Sm mRNA-LNP vaccine at inducing antibody and cellular immune responses in mice. Evaluation of the immunogenicity and efficacy of the S mRNA vaccine in piglets confirmed that it induced robust PEDV-specific humoral and cellular immune responses . Importantly, the S mRNA-LNP vaccine not only protected actively immunized piglets against PEDV but also equipped neonatal piglets with effective passive anti-PEDV immunity in the form of colostrum-derived antibodies after the immunization of sows. Our findings suggest that the PEDV-S mRNA-LNP vaccine is a promising candidate for combating PEDV infection.IMPORTANCEPorcine epidemic diarrhea virus (PEDV) continues to harm the global swine industry. It is important to develop a highly effective vaccine to control PEDV infection. Here, we report a PEDV spike (S) mRNA vaccine that primes a potent antibody response and antigen-specific T-cell responses in immunized piglets. Active and passive immunization can protect piglets against PED following the virus challenge. This study highlights the efficiency of the PEDV-S mRNA vaccine and represents a viable approach for developing an efficient PEDV vaccine.
Topics: Animals; Swine; Female; Mice; Antibodies, Viral; mRNA Vaccines; Porcine epidemic diarrhea virus; Viral Vaccines; Coronavirus Infections; Spike Glycoprotein, Coronavirus; Diarrhea; RNA, Messenger; Swine Diseases
PubMed: 38231557
DOI: 10.1128/mbio.02958-23 -
Autophagy Aug 2023Macroautophagy/autophagy is a cellular degradation and recycling process that maintains the homeostasis of organisms. The protein degradation role of autophagy has been...
Macroautophagy/autophagy is a cellular degradation and recycling process that maintains the homeostasis of organisms. The protein degradation role of autophagy has been widely used to control viral infection at multiple levels. In the ongoing evolutionary arms race, viruses have developed various ways to hijack and subvert autophagy in favor of its replication. It is still unclear exactly how autophagy affects or inhibits viruses. In this study, we have found a novel host restriction factor, HNRNPA1, that could inhibit PEDV replication by degrading viral nucleocapsid (N) protein. The restriction factor activates the HNRNPA1-MARCHF8/MARCH8-CALCOCO2/NDP52-autophagosome pathway with the help of transcription factor EGR1 targeting the promoter. HNRNPA1 could also promote the expression of IFN to facilitate the host antiviral defense response for antagonizing PEDV infection through RIGI protein interaction. During viral replication, we found that PEDV can, in contrast, degrade the host antiviral proteins HNRNPA1 and others (FUBP3, HNRNPK, PTBP1, and TARDBP) through its N protein through the autophagy pathway. These results reveal the dual function of selective autophagy in PEDV N and host proteins, which could promote the ubiquitination of viral particles and host antiviral proteins and degradation both of the proteins to regulate the relationship between virus infection and host innate immunity. 3-MA: 3-methyladenine; ATG: autophagy related; Baf A1: bafilomycin A; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; ChIP: chromatin immunoprecipitation; Co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; GPI: glycosyl-phosphatidylinositol; hpi: hours post infection; MARCHF8/MARCH8: membrane-associated ring-CH-type finger 8; MOI: multiplicity of infection; N protein: nucleocapsid protein; PEDV: porcine epidemic diarrhea virus; siRNA: small interfering RNA; TCID: 50% tissue culture infectious doses.
Topics: Animals; Swine; Porcine epidemic diarrhea virus; Macroautophagy; Autophagy; Antiviral Agents; Nucleocapsid Proteins; Coronavirus Infections
PubMed: 36861818
DOI: 10.1080/15548627.2023.2181615 -
Journal of Veterinary Internal Medicine 2023Nucleoside analog GS-441524 is effective in treating cats with feline infectious peritonitis (FIP). Investigation into the use of parent nucleotide analog remdesivir...
BACKGROUND
Nucleoside analog GS-441524 is effective in treating cats with feline infectious peritonitis (FIP). Investigation into the use of parent nucleotide analog remdesivir (GS-5734) is needed.
OBJECTIVES
To assess efficacy and tolerability of remdesivir with or without transition to GS-441524 in cats with FIP and document clinical and clinicopathologic progression over 6 months.
ANIMALS
Twenty-eight client-owned cats with FIP.
METHODS
Cats were prospectively recruited between May 2021 and May 2022. An induction dosage of remdesivir 10 to 15 mg/kg intravenously or subcutaneously q24h was utilized for 4 doses, with a maintenance dosage of remdesivir (6-15 mg/kg SC) or GS-441524 (10-15 mg/kg per os) every 24 hours continued for at least 84 days. Laboratory testing, veterinary, and owner assessments were recorded.
RESULTS
Twenty-four cats survived to 6 months (86%). Three cats died within 48 hours. Excluding these, survival from 48 hours to 6 months was 96% (24/25). Remission was achieved by day 84 in 56% (14/25). Three cats required secondary treatment for re-emergent FIP. Remission was achieved in all 3 after higher dosing (15-20 mg/kg). Adverse reactions were occasional site discomfort and skin irritation with remdesivir injection. Markers of treatment success included resolution of pyrexia, effusions, and presenting signs of FIP in the first half of treatment and normalization of globulin concentration, and continued body weight gains in the latter half of the treatment period.
CONCLUSIONS AND CLINICAL IMPORTANCE
Parenteral administration of remdesivir and oral administration of GS-441524 are effective and well-tolerated treatments for FIP. Early emphasis on clinical, and later emphasis on clinicopathologic response, appears prudent when monitoring treatment efficacy.
Topics: Humans; Cats; Animals; Feline Infectious Peritonitis; Exudates and Transudates; Coronavirus, Feline; Cat Diseases
PubMed: 37439383
DOI: 10.1111/jvim.16803 -
Journal of Feline Medicine and Surgery Aug 2023Feline infectious peritonitis (FIP), a common disease in cats caused by feline coronavirus (FCoV), is usually fatal once clinical signs appear. Successful treatment of...
OBJECTIVES
Feline infectious peritonitis (FIP), a common disease in cats caused by feline coronavirus (FCoV), is usually fatal once clinical signs appear. Successful treatment of FIP with oral GS-441524 for 84 days was demonstrated recently by this research group. The aim of this study was to evaluate the long-term outcome in these cats.
METHODS
A total of 18 successfully treated cats were followed for up to 1 year after treatment initiation (9 months after completion of the antiviral treatment). Follow-up examinations were performed at 12-week intervals, including physical examination, haematology, serum biochemistry, abdominal and thoracic ultrasound, FCoV ribonucleic acid (RNA) loads in blood and faeces by reverse transciptase-quantitative PCR and anti-FCoV antibody titres by indirect immunofluorescence assay.
RESULTS
Follow-up data were available from 18 cats in week 24, from 15 cats in week 36 and from 14 cats in week 48 (after the start of treatment), respectively. Laboratory parameters remained stable after the end of the treatment, with undetectable blood viral loads (in all but one cat on one occasion). Recurrence of faecal FCoV shedding was detected in five cats. In four cats, an intermediate short-term rise in anti-FCoV antibody titres was detected. In total, 12 cats showed abdominal lymphadenomegaly during the follow-up period; four of them continuously during the treatment and follow-up period. Two cats developed mild neurological signs, compatible with feline hyperaesthesia syndrome, in weeks 36 and 48, respectively; however, FCoV RNA remained undetectable in blood and faeces, and no increase in anti-FCoV antibody titres was observed in these two cats, and the signs resolved.
CONCLUSIONS AND RELEVANCE
Treatment with GS-441524 proved to be effective against FIP in both the short term as well as the long term, with no confirmed relapse during the 1-year follow-up period. Whether delayed neurological signs could be a long-term adverse effect of the treatment or associated with a 'long FIP syndrome' needs to be further evaluated.
Topics: Cats; Animals; Feline Infectious Peritonitis; Follow-Up Studies; Polymerase Chain Reaction; RNA, Viral; Coronavirus, Feline; Cat Diseases
PubMed: 37548535
DOI: 10.1177/1098612X231183250 -
Journal of Virology Jun 2023Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various...
Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having a specific interaction with the PEDV S protein, and positive regulation of PEDV infection was validated by knockdown and overexpression tests. Further studies verified the role of HSPA5 in viral attachment and internalization. In addition, we found that HSPA5 interacts with S proteins through its nucleotide-binding structural domain (NBD) and that polyclonal antibodies can block viral infection. In detail, HSPA5 was found to be involved in viral trafficking via the endo-/lysosomal pathway. Inhibition of HSPA5 activity during internalization would reduce the subcellular colocalization of PEDV with lysosomes in the endo-/lysosomal pathway. Together, these findings show that HSPA5 is a novel PEDV potential target for the creation of therapeutic drugs. PEDV infection causes severe piglet mortality and threatens the global pig industry. However, the complex invasion mechanism of PEDV makes its prevention and control difficult. Here, we determined that HSPA5 is a novel target for PEDV which interacts with its S protein and is involved in viral attachment and internalization, influencing its transport via the endo-/lysosomal pathway. Our work extends knowledge about the relationship between the PEDV S and host proteins and provides a new therapeutic target against PEDV infection.
Topics: Animals; Chlorocebus aethiops; Coronavirus Infections; Lysosomes; Porcine epidemic diarrhea virus; Spike Glycoprotein, Coronavirus; Swine; Swine Diseases; Vero Cells; Virus Internalization; Endoplasmic Reticulum Chaperone BiP; Virus Attachment; Endocytosis
PubMed: 37222617
DOI: 10.1128/jvi.00549-23 -
Journal of Veterinary Internal Medicine 2023GS-441524 has been successfully used to treat feline infectious peritonitis (FIP) in cats. However, the use of its prodrug, remdesivir, in combination with a PO...
BACKGROUND
GS-441524 has been successfully used to treat feline infectious peritonitis (FIP) in cats. However, the use of its prodrug, remdesivir, in combination with a PO GS-441524 containing product for the treatment of FIP has not yet been described.
OBJECTIVES
Describe treatment protocols, response to treatment and outcomes in cats with FIP treated with a combination of PO GS-441524 and injectable remdesivir.
ANIMALS
Thirty-two client-owned cats diagnosed with effusive or non-effusive FIP including those with ocular and neurological involvement.
METHODS
Cats diagnosed with FIP at a single university hospital between August 2021 and July 2022 were included. Variables were recorded from time of diagnosis, and subsequent follow-up information was obtained from the records of referring veterinarians. All surviving cats were observed for the entire 12-week treatment period.
RESULTS
Cats received treatment with different combinations of IV remdesivir, SC remdesivir, and PO GS-441524 at a median (range) dosage of 15 (10-20) mg/kg. Clinical response to treatment was observed in 28 of 32 cats (87.5%) in a median (range) of 2 (1-5) days. Twenty-six of 32 cats (81.3%) were alive and in clinical and biochemical remission at the end of the 12-week treatment period. Six of 32 cats (18.8%) died or were euthanized during treatment with 4 of the 6 cats (66%) dying within 3 days of starting treatment.
CONCLUSIONS
We describe the effective use of injectable remdesivir and PO GS-441524 for the treatment of FIP in cats. Success occurred using different treatment protocols and with different presentations of FIP including cats with ocular and neurological involvement.
Topics: Humans; Cats; Animals; Feline Infectious Peritonitis; Coronavirus, Feline; Cat Diseases
PubMed: 37403259
DOI: 10.1111/jvim.16804 -
Journal of Virology Nov 2023Porcine epidemic diarrhea caused by porcine coronaviruses remains a major threat to the global swine industry. Fatty acids are extensively involved in the whole life of...
Porcine epidemic diarrhea caused by porcine coronaviruses remains a major threat to the global swine industry. Fatty acids are extensively involved in the whole life of the virus. In this study, we found that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) significantly reduced the viral load of porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine delta coronavirus (PDCoV) and acted on the replication of the viruses rather than attachment and entry. We further confirmed that DHA and EPA inhibited PEDV replication by alleviating the endoplasmic reticulum stress. Meanwhile, DHA and EPA alleviate PEDV-induced inflammation and reactive oxygen species (ROS) levels and enhance the cellular antioxidant capacity. These data indicate that DHA and EPA have antiviral effects on porcine coronaviruses and provide a molecular basis for the development of new fatty acid-based therapies to control porcine coronavirus infection and transmission.
Topics: Animals; Coronavirus; Coronavirus Infections; Docosahexaenoic Acids; Eicosapentaenoic Acid; Porcine epidemic diarrhea virus; Swine; Swine Diseases; Transmissible gastroenteritis virus; Virus Replication; Endoplasmic Reticulum Stress
PubMed: 37843366
DOI: 10.1128/jvi.01209-23 -
Viruses Sep 2023Emerging and re-emerging swine coronaviruses (CoVs), including porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea... (Review)
Review
Emerging and re-emerging swine coronaviruses (CoVs), including porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome-CoV (SADS-CoV), cause severe diarrhea in neonatal piglets, and CoV infection is associated with significant economic losses for the swine industry worldwide. Reverse genetics systems realize the manipulation of RNA virus genome and facilitate the development of new vaccines. Thus far, five reverse genetics approaches have been successfully applied to engineer the swine CoV genome: targeted RNA recombination, in vitro ligation, bacterial artificial chromosome-based ligation, vaccinia virus -based recombination, and yeast-based method. This review summarizes the advantages and limitations of these approaches; it also discusses the latest research progress in terms of their use for virus-related pathogenesis elucidation, vaccine candidate development, antiviral drug screening, and virus replication mechanism determination.
Topics: Animals; Swine; Coronavirus; Reverse Genetics; Coronavirus Infections; Porcine epidemic diarrhea virus; RNA; Diarrhea; Swine Diseases
PubMed: 37896780
DOI: 10.3390/v15102003