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Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3'-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5'-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently.

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.

Feline enteric coronavirus (FECoV) causes subclinical infection; therefore, asymptomatic cats can act as transmitters of FECoV. However, there have been few studies on the prevalence of FECoV in asymptomatic cats in Japan. In this study, we used a nested RT-PCR assay targeting the S gene of FECoV to test 319 normal fecal samples from stray cats and domestic cats in Japan between 2019 and 2020. Seventy-five samples tested positive, and the presence of FECoV in domestic cats was significantly associated with age (p < 0.01), but not with gender, breed, or living in a multi-cat household. The results provide insights into the current prevalence of FECoV in asymptomatic cats in Japan.

A comparative genomic analysis of feline coronavirus (FCoV) and feline panleukopenia virus (FPLV) was performed. Based on the conserved regions of the two viruses, specific probes and real-time PCR (qPCR) primers were designed, and a duplex TaqMan qPCR-based assay was established for detecting FCoV and FPLV. The results showed high analytical specificity, and no cross-response with other feline viruses was observed. This method is highly versatile and can be used to detect all FCoV strains stored in laboratories and recombinant plasmids constructed according to the sequences of blank FCoV strains in laboratories. The analytical sensitivity of this method in detecting FCoV and FPLV was as low as 50 copies/μL, which is approximately 20-fold greater than that of conventional PCR. The coefficients of variation (CVs) for the intra- and interbatch coefficients of variation were less than 2%. After 75 clinical samples were tested, the percentage of FCoV- and FPLV-positive samples was 5.34% greater than that of conventional PCR methods, a finding robustly supported by sequencing identification. As validated by clinical samples, the method was sensitive, specific, general, and reproducible and holds great potential for the rapid identification and diagnosis of FCoV and FPLV infections, as well as for epidemiological investigations. Key points • One-step duplex TaqMan real-time PCR detection method can detect FCoV and FPLV in clinical samples simultaneously and steadily. • Almost all the currently known FCoV and FPLV strains can be detected. • This method has high sensitivity, specificity and generality.

The main protease, M pro (or 3CL pro ) 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 M pro from both SARS-CoV and SARS-CoV-2 with IC 50 values in the nanomolar range. Crystal structures of SARS-CoV-2 M pro 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. Coronavirus main protease is essential for viral polyprotein processing and replication. Here Vuong et al. report efficient inhibition of SARS-CoV-2 replication by the dipeptide-based protease inhibitor GC376 and its parent GC373, which were originally used to treat feline coronavirus infection.

Feline coronavirus (FCoV) is an enveloped, positive‐sense RNA virus, which is widespread among feline populations, and can cause a fatal serious disease called feline infectious peritonitis (FIP). According to the differences of antigen and genetic composition, FCoV consists of two genotypes, FCoV I and FCoV II. In this study, we have isolated and identified a FCoV I strain named HL2019. Based on the complete genome of HL2019, phylogenetic analysis showed that HL2019 strain formed in the cluster FCoV I which is more closed to human coronavirus 229E (HCoV 229E) and HCoV NL63, while the FCoV I stains is distantly related to FCoV II strains. Analyzing with RDP4 and Simplot software showed that the virus HL2019 is recombinant by the FCoV I China/ZJU1709 and FCoV I Netherlands/UU16 strains. Furthermore, the pathogenicity of HL2019 was evaluated in 9–12‐month‐old cats. Two of three challenged cats developed serious clinical signs and died at 28‐day postchallenge (dpc). Real‐time polymerase chain reaction (PCR) analysis showed that HL2019 has broad tissue tropism, especially in the duodenum with viral load up to 10 4  copies/mg. In summary, our data show that we have successfully isolated a strain of FCoV I named HL2019 that is highly pathogenic to cats.

Feline infectious peritonitis (FIP) is a systemic, potentially fatal viral disease. The objectives of this study were to review clinical and laboratory features and treatment of cats highly suspected of FIP in Wuhan, China. The clinical records of 127 cats highly suspected of FIP were reviewed for history, clinical signs, physical findings, and diagnostic test results. Sex, neutering status, breed, age, and month of onset of disease were compared with the characteristics of the clinic population. Age and neutering status were significantly correlated with FIP-suspicion. Sex, breed and onset month were not associated with FIP. There were many more FIP-suspected cases in cats in young cats or male intact cats. Effusion was observed in 85.8% of the FIP-suspected cats. Increased serum amyloid A (SAA) and lymphopenia were common laboratory abnormalities in the FIP cases. Furthermore, 91.7% of the cats highly suspected of FIP had an albumin/globulin (A/G) ratio < 0.6, while 85.3% had an A/G ratio < 0.5. The mortality rate for FIP-suspected cats was 67%, and six submitted cases were confirmed by FIP-specific immunohistochemistry. Of the 30 cats treated with GS-441524 and/or GC376, 29 were clinically cured. The study highlights the diverse range of clinical manifestations by clinicians in diagnosing this potentially fatal disease. A/G ratio and SAA were of higher diagnostic value. GS-441524 and GC376 were efficient for the treatment of FIP-suspected cats.

Alphacoronaviruses are widespread but understudied in comparison to betacoronaviruses. Within the alphacoronaviruses is the species , which comprises distinct viruses of cats, dogs, and pigs, along with a separate species that infects mustelids-as well as other related viruses of pigs and circulating human viruses. High-pathogenicity feline coronavirus (FCoV) is infamous as the cause of feline infectious peritonitis (FIP), existing as two distinct genotypes (types 1 and 2) and transmitted as a low-pathogenicity virus. The high-pathogenicity variants arise in cats infected with FCoV, and while the mutations responsible remain enigmatic, the main determinant is the spike glycoprotein. FCoV-1 disease outcome is driven by a combination of both within- and between-host evolution. Virulence can be largely explained by the \"internal mutation hypothesis,\" which argues that high-pathogenicity-but poorly transmissible-variants are selected in individual cats. Canine coronaviruses are generally considered low pathogenicity but can cause severe enteritis and can be systemic. Notably, the canine coronavirus spike gene periodically recombines with FCoV-1 to generate FCoV-2, exemplified by FCoV-23, which has caused a widespread outbreak of FIP in Cyprus and has a notably truncated spike N-terminal domain (NTD). In pigs, coronaviruses often cause severe gastrointestinal disease but can become respiratory and have low pathogenicity based on what can also be considered an \"internal deletion\" of the spike NTD. These viruses may exist as a dynamic \"metavirome\" (the sum of all viral genomes present in a sample) that is in a constant state of flux, presenting notable challenges for disease surveillance and management.

This study was conducted to identify the molecular and biological characteristics of the collected feline coronavirus (FCoV) strains in northern Vietnam. A total of 166 fecal samples were collected from domestic cats in Hanoi, Bacgiang, Hungyen, and Hanam in northern Vietnam. Conventional polymerase chain reaction (PCR) was used to detect the FCoV genome in the field samples. Results indicated that 19 (11.45%) out of 166 fecal samples were positive for the FCoV genome using PCR. Insignificant differences in positive rates were detected according to breed, age, sex, and health status of the cats. By using nested PCR, all 19 FCoV strains obtained belonged to type I. Analysis of the partial S gene sequences indicated that the nine Vietnamese FCoV strains in this study shared high nucleotide identity, ranging from 88.5% to 99.16%. Phylogenetic analysis supported that the Vietnamese FCoV strains obtained were type I viruses, which are divided into several clades. The nine Vietnamese FCoV strains were genetically close to viruses from the Netherlands, France, and China and differed from the vaccine strain. No mutation was detected among the nine Vietnamese FCoV strains at sites 23,531 and 23,537 in the S gene sequences. The S1/S2 cleavage site on the S protein of FCoV of the nine viral strains indicated an R/G-R-S/A-R-R-S motif, which was typical for feline enteric coronavirus strains. The sequences found were consistent with FECV/low-path viruses, and that it was healthy cats (not FIP cats) that were sampled.

Feline infectious peritonitis virus (FIPV) remains as one of the leading causes of morbidity and mortality in young cats from shelters and catteries worldwide. Since little is known about the molecular characteristics of currently circulating FIPV strains in Long Island, New York, samples from two shelter cats submitted to the Pathology Diagnostic Services of the Long Island University College of Veterinary Medicine, with gross and microscopic lesions consistent with those of FIP were processed for virus isolation, molecular characterization and full-length genome decoding. The younger shelter cat, a 1-year-old male (A15) was found dead without previous signs of illness. Postmortem examination revealed gross and microscopic lesions characterized by vasculitis, necrosis, hemorrhage, and pyogranulomatous inflammation confined to the colon and associated lymph nodes. The second cat, a 7-year-old spayed female (A37) had an identical clinical history and similar but widespread lesions, including fibrinous peritoneal effusion, cecal, colonic, renal, and hepatic involvement. The gross and microscopic diagnosis of FIP in these cats was confirmed by immunohistochemistry (IHC) demonstration of feline coronavirus antigen using mouse anti-FIPV3-70 monoclonal antibody. Virus isolation from saved frozen kidney and colon tissue was performed through several subsequent blind passages in MDCK and Vero cell lines. Confirmation of the FIPV isolation was done through qRT-PCR, IFA, western blot using N protein antibodies, and NGS of the full-length genome sequencing. The full-length genome sequences of the virus isolate from the two cats were decoded using next-generation sequencing (NGS) and deposited in the GenBank as accession numbers PQ192636 and PQ202302. The genome size of these isolates was (29355 and 29321) nucleotides (nt) in length, respectively. While their genome organization was consistent with other FIPV genomes as follows (5’UTR-ORF1ab-S-3abc-M-E-7b-3’UTR-3’), marked differential mutations were observed in the ORF1a/b, S, 3Abc, and 7b protein genes of the two FIPV isolates. One notable deletion of 34 nucleotides was observed in the 7b genes of one of these isolates but was absent in the other. We confirmed the potential recombination events during the evolution of those two FIPV field isolates with the potential parent virus as FECoV-US isolated in 1970 and the potential minor parent as the Canine coronavirus. Our results provide a comprehensive molecular analysis of two novel FIPV isolates causing fatal disease in shelter cats from Long Island. Diagnostic surveillance with molecular characterization and sequencing analysis of circulating FIPV strains within animal shelters may help early detect unique emerging clinical and pathological manifestations of the disease and develop more targeted prophylactic and therapeutic approaches to control it.