Explore the vast range of titles available.

Penicillide is the founder product of a class of natural products of fungal origin. Although this compound and its analogues have been identified from taxonomically heterogeneous fungi, they are most frequently and typically reported from the species of Talaromyces and Penicillium. The producing strains have been isolated in various ecological contexts, with a notable proportion of endophytes. The occurrence of penicillides in these plant associates may be indicative of a possible role in defensive mutualism based on their bioactive properties, which are also reviewed in this paper. The interesting finding of penicillides in fruits and seeds of Phyllanthus emblica is introductory to a new ground of investigation in view of assessing whether they are produced by the plant directly or as a result of the biosynthetic capacities of some endophytic associates.

Bovine herpesvirus 1 (BoHV-1) productive infection stimulates β-catenin-dependent transcription to facilitate virus replication. Phosphoglycerate kinase 1 (PGK1), which catalyses the initial step of ATP production during glycolysis, also has a mitochondrial form that is implicated in tissue injury across various diseases. However, the relationship between BoHV-1 replication and the PGK1 signalling pathway is not yet fully understood. In this study, we discovered that PGK1 signalling significantly influences BoHV-1 replication, with the virus infection leading to a marked increase in the accumulation of PGK1 proteins in mitochondria. Overexpression of β-catenin reduces PGK1 steady-state protein levels while overexpressing PGK1 boosts β-catenin protein expression—a phenomenon that reverses upon virus infection. Importantly, consistent with PGK1’s vital role in virus replication, PGK1 stimulates β-catenin-dependent transcriptional activity, partly by promoting the nuclear accumulation of transcriptionally active β-catenin and phospho-β-catenin (S552) in virus-infected cells. In summary, our findings suggest for the first time that PGK1 signalling may be involved in BoHV-1 replication and contribute to virus pathogenicity.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that interacts with substrates, including microbial metabolites. Recent advances reveal that AhR is involved in the host response to coronaviruses (CoVs) infection. Particularly, AhR antagonists decrease the expression of angiotensin-converting enzyme 2 (ACE2) via AhR up-regulation, resulting in suppression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in mammalian cells. Herein, we report that AhR is expressed in canine fibrosarcoma (A72) cells, where it is considerably activated by infection with genotype II of canine coronavirus (CCoV-II). The pharmacological inhibition of AhR, by CH223191, suppressed cell death signs and increased cell viability. Furthermore, the AhR antagonist induced a meaningful decline in virus yield, accompanied by the inhibition of the expression of viral nuclear protein (NP). Fascinatingly, during CCoV infection, a novel co-expression of NP and AhR expression was found. Taken together, our preliminary findings show that infection with CCoV activates AhR, and pharmacologic AhR inhibition reduces CCoV replication, identifying AhR as a possible candidate target for CCoV antiviral therapy.

Viral and chemical analyses were performed on 80 dead cats and 51 dead dogs from the Campania Region (Southern Italy), with the aim of evaluating in vivo the potential correlation between coronavirus (CoV) infections and levels of environmental pollutants such as dioxins and PCSs (PCDD/F, DL-PCB and NDL-PCB). The overall viral prevalence was 16.3% in cats and 23.5% in dogs. Both feline coronavirus (FCoV) and canine coronavirus (CCoV) were identified, with variable detection rates in all the other organs investigated, supporting studies that provide evidence of systemic viral spread. The highest prevalence of coronaviruses (CoVs) was observed in Naples (19.2% for FCoV; 30.7% for CCoV) and Caserta (11.1% for FCoV; 50.0% for CCoV), areas that include municipalities with the highest Municipality Index of Environmental Pressure (MIEP) scores. Chemical analyses showed that DL-PCBs were present at more elevated concentrations in CoV-infected dogs and cats than in non-infected animals, whereas ∑NDL-PCB and ∑PCDD/F were detected in greater amounts in non-infected subjects. Among PCDDs, the congener 2,3,7,8-TCDD displayed different distribution patterns between infected and non-infected animals. In cats, 70.0% of FCoV-positive individuals had 2,3,7,8-TCDD levels above the limit of quantification (LOQ), compared with 38.0% of FCoV-negative cats. In dogs, 78.0% of CCoV-infected animals exceeded the LOQ, compared with 20.0% of non-infected ones; this difference was statistically significant. The results of the study suggest that elevated levels of 2,3,7,8-TCDD may be associated with CCoV infection and replication in dogs, suggesting a possible relationship between environmental pollution and susceptibility to coronavirus infections.

A 4-year retrospective study (2016–2019) of selected routine bacteriological examinations of the veterinary microbiology laboratory of the University Veterinary Teaching Hospital of Naples (Italy) was carried out. A total of 189 bacteriological samples were collected from 171 dogs and 18 cats suffering from skin infections. In dogs, the most common cutaneous infection was otitis externa, while pyoderma was found to be prevalent in cats. The number of recorded Gram-positive strains over the study period did not vary considerably from year to year and was always significantly higher (p-value = 0.0007) in comparison with Gram-negative bacterial isolations. In dogs, Staphylococcus pseudintermedius was the most common identified Gram-positive bacterium (65%), while Pseudomonas aeruginosa (36%) was the one among the isolated Gram-negative bacteria. In cats, coagulase-negative staphylococci were the most predominant isolated bacteria (47%). The phenotypic profiles of antibiotic resistance showed that most of the strains were resistant to amoxicillin–clavulanate, penicillin, clindamycin, and trimethoprim–sulfamethoxazole. Several multi-drug-resistant strains (35%) were detected in canine isolates. An updating of antibiotic resistance profiles of the main Gram-positive and Gram-negative bacteria principally associated with skin infections of pet animals is necessary to improve stewardship programs of veterinary hospitals and clinics.

The scientific community’s interest in natural compounds with antiviral properties has considerably increased after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), especially for their potential use in the treatment of the COVID-19 infection. From this perspective, bovine coronavirus (BCoV), member of the genus β-CoV, represents a valuable virus model to study human β-CoVs, bypassing the risks of handling highly pathogenic and contagious viruses. Pimarane diterpenes are a significant group of secondary metabolites produced by phytopathogenic fungi, including several Diplodia species. Among the members of this class of natural products, sphaeropsidin A (SphA) and its analog sphaeropsidin B (SphB) are well known for their bioactivities, such as antimicrobial, insecticidal, herbicidal, and anticancer. In this study, the antiviral effects of SphA and SphB were evaluated for the first time on bovine (MDBK) cells infected with BCoV. Our findings showed that both sphaeropsidins significantly increased cell viability in infected cells. These substances also caused substantial declines in the virus yield and in the levels of the viral spike S protein. Interestingly, during the treatment, a cellular defense mechanism was detected in the downregulation of the aryl hydrocarbon receptor (AhR) signaling, which is affected by BCoV infection. We also observed that the presence of SphA and SphB determined the deacidification of the lysosomal environment in infected cells, which may be related to their antiviral activities. In addition, in silico investigations have been performed to elucidate the molecular mechanism governing the recognition of bovine AhR (bAhR) by Sphs. Molecular docking studies revealed significant insights into the structural determinants driving the bAhR binding by the examined compounds. Hence, in vitro and in silico results demonstrated that SphA and SphB are promising drug candidates for the development of efficient therapies able to fight a β-CoV-like BCoV during infection.

Canine coronavirus type II (CCoV-II), an alphacoronavirus, is responsible for mild enteritis, especially in puppies, but due to its plasticity, it can also cause serious diseases in humans. Formyl peptide receptors (FPRs) play an important role in modulating immune responses, and their expression is variably regulated by cell type and by viral infections. In this study, the role of FPR2 during CCoV infection in a canine fibrosarcoma (A72 cells) cell line as well as in a feline Crandell-Rees Feline Kidney (CRFK) cell line was investigated by in vitro and in silico approaches. During infection, in the presence of WRW4, a specific FPR2 inhibitor, a reduction in gene and protein levels of FPR2 in CCoV infected cells was observed. These results were accompanied by worsened changes in cell viability and morphology in the treated-infected groups, which exhibited substantial growth in virus yield and a significant increase in both gene and protein expression of viral nucleocapsid protein (NP). Interestingly, an opposite trend in the above assays was observed following infection with HP2-20, an agonist of FPR2. The 3D model of canine FPR2 ( c FPR2) showed that WRW4 was confined to the c FPR2 core and did not interact with the extramembrane loops of the receptor, whereas HP2-20 contacted both the core and the second extracellular loop of c FPR2 (ECL2). In addition, the complex c FPR2/HP2-20 exhibited a marked increase in the number of H-bonds, hydrophobic interactions and electrostatic charges compared to the complex c FPR2/WRW4. In conclusion, these results showed that CCoV replication is related to FPR2, suggesting it as an interesting target to develop new drugs to fight CoVs infection.

Feline coronavirus (FCoV) is an alphacoronavirus (αCoV) that causes moderate or chronic asymptomatic infection in cats. However, in a single infected cat, FCoV can modify its cellular tropism by acquiring the ability to infect macrophages, resulting in the development of feline infectious peritonitis (FIP). In this context, to restrain the impact of FCoV infection, scientific research has focused attention on the development of antiviral therapies involving novel mechanisms of action. Recent studies have demonstrated that aryl hydrocarbon receptor (AhR) signaling regulates the host response to different human and animal CoVs. Hence, the mechanism of action of AhR was evaluated upon FCoV infection in Crandell Feline Kidney (CRFK) and in canine fibrosarcoma (A72) cells. Following infection with feline enteric CoV (FECV), strain “München”, a significant activation of AhR and of its target CYP1A1, was observed. The selective AhR antagonist CH223191 provoked a reduction in FCoV replication and in the levels of viral nucleocapsid protein (NP). Furthermore, the effect of the AhR inhibitor on the acidity of lysosomes in infected cells was observed. Our findings indicate that FCoV acts on viral replication that upregulates AhR. CH223191 repressed virus yield through the inhibition of AhR. In this respect, for counteracting FCoV, AhR represents a new target useful for identifying antiviral drugs. Moreover, in the presence of CH223191, the alkalinization of lysosomes in FCoV-infected CRFK cells was detected, outlining their involvement in antiviral activity.

The importance of wild boar lies in its role as a bioindicator for the control of numerous zoonotic and non-zoonotic diseases, including antibiotic resistance. Mannitol Salt Agar (MSA) is a selective medium used for isolation, enumeration, and differentiation of pathogenic staphylococci. Other genera such as Enterococcus spp. are also salt tolerant and able to grow on MSA. The present study focused on the identification, by matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), of bacteria grown on MSA isolated from the nasal cavities of 50 healthy wild boars hunted in Campania Region (southern Italy) in the year 2019. In addition, the antimicrobial resistance phenotype of the isolated strains was determined by disk diffusion method. Among genus Staphylococcus, coagulase-negative Staphylococcus (CoNS) were the most common isolated species, with Staphylococcus xylosus as the most prevalent species (33.3%). Furthermore, Enterococcus spp. strains were isolated, and Enterococcus faecalis was the species showing the highest frequency of isolation (93.8%). For staphylococci, high levels of resistance to oxacillin (93.3%) were recorded. Differently, they exhibited low frequencies of resistance to tested non-β-lactams antibiotics. Among enterococci, the highest resistances were observed for penicillin (93.7%), followed by ampicillin (75%), and ciprofloxacin (68.7%). Interestingly, 43.7% of the isolated strains were vancomycin-resistant. In conclusion, this study reports the phenotypic antibiotic resistance profiles of Staphylococcus spp. and Enterococcus spp. strains isolated from nasal cavities of wild boars hunted in Campania Region, highlighting that these wild animals are carriers of antibiotic resistant bacteria.

The recent COVID-19 pandemic has prompted the scientific community to prioritize the discovery of preventive methods and new therapeutics, including the investigation of natural compounds with antiviral potential. Fungal secondary metabolites (SMs) represent a promising source of antiviral drugs due to their structural diversity and intrinsic biocompatibility. Herein, the antiviral activity of 6-pentyl-α-pyrone (6PP) against bovine coronavirus (BCoV) has been evaluated in vitro. Considering that BCoV and SARS-CoV-2 are both members of the Betacoronavirus genus and share several key features, BCoV represents a valuable reference model for human coronavirus research. A non-cytotoxic dose of 6PP was used on MDBK cells to evaluate its antiviral activity against BCoV. Different experimental conditions were employed to examine cell monolayer protection both pre- and post-infection, as well as the potential inhibition of viral internalization. Overall, post-infection 6PP treatment reduced viral load and decreased viral internalization. Results were analyzed using viral titration and quantitative PCR, while data interpretation was performed by statistical software tools. This study presents a novel fluorescence quantification approach with high confidence demonstrated by its significant concordance with RT-qPCR results. These data suggest that 6PP could be an effective antiviral agent for BCoV, warranting further investigation of its role in coronavirus inhibition.