Search Results (261)

Background/Objectives: Viral respiratory infections have a significant impact on global health and the economy. While vaccines are effective in preventing infection, they might not be available or sufficient when used alone and must be complemented by specific therapeutic strategies. The development of new antiviral agents is increasingly important due to the continual emergence of novel respiratory pathogens. Previously we identified bovine lactoferrin (bLf)-derived tetrapeptides and peptidomimetics that showed potent in vitro activity against the influenza A virus in the picomolar range. Methods: Inspired by these results, in this study, we evaluated the antiviral potential of these compounds against HCoV-229E, a human coronavirus that can cause severe disease in immunocompromised individuals, using a compound repositioning approach. Results: Functional studies revealed that SK(N-Me)HS (3) interferes with viral entry and replication, while compound SNKHS (5) primarily blocks infection in the early stages. Biophysical analyses confirmed the occurrence of high-affinity binding to the viral spike protein, and computational studies suggested that the compounds target a region involved in conformational changes necessary for membrane fusion. Conclusions: These findings highlight these compounds as promising candidates for coronavirus entry inhibition and underscore the value of compound repurposing in antiviral development. Full article

The seasonal patterns of viral diseases in farm animals present significant challenges to global livestock productivity, with cold stress emerging as a potential modulator of host–pathogen interactions. This review synthesizes current knowledge on the expression dynamics of heat shock protein 70 (HSP70) in farm animals under cold-stress conditions and its potential roles as (1) a viral replication facilitator and (2) an immune response regulator. This review highlights cold-induced HSP70 overexpression in essential organs, as well as its effects on significant virus life cycles, such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and bovine viral diarrhea virus (BVDV), through processes like viral protein chaperoning, replication complex stabilization, and host defense modulation. By integrating insights from thermophysiology, virology, and immunology, we suggest that HSP70 serves as a crucial link between environmental stress and viral disease seasonality. We also discuss translational opportunities targeting HSP70 pathways to break the cycle of seasonal outbreaks, while addressing key knowledge gaps requiring further investigation. This article provides a framework for understanding climate-driven disease patterns and developing seasonally adjusted intervention strategies. Full article

Bovine respiratory disease complex (BRDC) is one of the primary causes of morbidity, mortality, and economic loss in cattle worldwide. Accurate and rapid identification of causative pathogenic agents is essential for effective disease management and control. In this study, a novel multiplex fluorescence-based quantitative polymerase chain reaction (qPCR) assay was developed for the simultaneous detection of eight major pathogens associated with BRDC. The targeted pathogens included the following: bovine viral diarrhea virus (BVDV), bovine parainfluenza virus type 3 (BPIV3), bovine respiratory syncytial virus (BRSV), bovine coronavirus (BcoV), Mycoplasma bovis (M.bovis), Pasteurella multocida (PM), Mannheimia haemolytica (MH), and infectious bovine rhinotracheitis virus (IBRV). The assay was rigorously optimized to ensure high specificity with no cross-reactivity among targets. The limit of detection (LOD) was determined to be as low as 5 copies per reaction for all target pathogens. The coefficient of variation (CVs) for both intra-assay and inter-assay measurements were consistently below 2%, demonstrating excellent reproducibility. To validate the clinical utility of the assay, a total of 1012 field samples were tested, including 504 nasal swabs from Farm A and 508 from Farm B in Jiangsu Province. BVDV, BcoV, PM, and MH were detected from Farm A, with a BVDV-positive rate of 21.63% (109/504), BcoV-positive rate of 26.79% (135/504), PM-positive rate of 28.77% (145/504), and MH-positive rate of 15.08% (76/504). Also, BcoV, PM, MH, and IBRV were detected from Farm B, with a BcoV-positive rate of 2.36% (12/508), PM-positive rate of 1.38% (7/508), MH-positive rate of 14.76% (75/508), and IBRV-positive rate of 5.51% (28/508). Notably, a significant proportion of samples showed evidence of mixed infections, underscoring the complexity of BRDC etiology and the importance of a multiplex diagnostic approach. In conclusion, the developed multiplex qPCR assay provides a reliable, rapid, and cost-effective tool for simultaneous detection of multiple BRDC-associated pathogens, which will hold great promise for enhancing disease surveillance, early diagnosis, and targeted intervention strategies, ultimately contributing to improved BRDC management and cattle health outcomes. Full article

Background: PP-007 (SANGUINATE^®, PEGylated carboxyhemoglobin, bovine) is under development to treat conditions of ischemia/hypoxia. Hemorrhagic/hypovolemic shock (H/HVS) becomes a life-threatening comorbidity due in part to hypotension and hypoxia. Blood transfusions are indicated, but supply and compatibility issues may limit subject access or when blood is not an option due to religious restriction or concern for clinical complications. PP-007 is universally compatible with an effective hydrodynamic radius and colloidal osmotic pressure facilitating perfusion without promoting extravasation. Methods: A review of previous clinical trials was performed and revealed an Open-Label Phase 1 safety study of acute severe anemia (hemoglobin ≤ 5 g/dL) in adult (≥18 y) patients unable to receive red blood cell transfusion (NCT02754999). Primary outcomes included safety events with secondary efficacy measures of organ function and survival at 1, 14, and 28 days. Additionally, a retrospective review of published, peer-reviewed case reports was performed, evaluating the administration of Sanguinate for Expanded Access in those patient populations where blood was not an option over the past 12 years. Results: A total of 103 subjects were enrolled in the Phase I safety study with significant co-morbidities that most commonly included hypertension (n = 43), acute and chronic kidney disease (n = 38), diabetes mellitus (n = 29), gastrointestinal bleeds (n = 18), and sickle cell disease (n = 13). Enrollment characteristics included decreased hemoglobin and severe anemia (mean baseline hemoglobin of 4.2 g/dL). Treatments included an average of three infusions [range 1–17]. Secondary efficacy measures were mean Hb levels, respiratory support, and vasopressor requirements, all demonstrating clinically relevant improvements. Fourteen additional cases were identified in the literature. Though one patient died due to pre-treatment conditions, all patients but one were discharged home in stable condition. Conclusion: Collectively, these observations are encouraging and provide support for the continued evaluation of PP-007 in advanced clinical trials in severe anemia including H/HVS. The review of published case reports underscored the potential of Sanguinate to reduce early mortality. Adverse effects included transient hypertension, lethargy, dizziness, and troponin elevation. These findings highlight the need for continued research and funding of blood alternatives to improve outcomes when standard blood transfusions are unavailable or contraindicated. Full article

Background/Objectives: Bovine respiratory disease (BRD) is a common disease impacting cattle throughout the US. BRD is a multifactorial disease as disease risk varies with the genetic profile of the host, environmental conditions, and pathogen exposure. Selection for enhanced BRD resistant cattle can aid in reducing BRD. The objectives of this study were to identify loci, gene sets, and genes associated and enriched for BRD in pre- and post-weaned Holstein cattle. Methods: Cases consisted of 2147 and 5607 calves treated for BRD as pre-weaned (0–60 days old) and post-weaned (61–420 days old) calves, respectively. Controls consisted of calves untreated for BRD that remained in the herd for 61 (n = 14,219) days for pre-weaned or 421 (n = 12,242) days for post-weaned calves. A genome-wide association analysis (GWAA) identified loci and positional candidate genes associated with BRD (uncorrected P < 1 × 10⁻⁵) for additive, dominant, and recessive inheritance models. A gene set enrichment analysis (GSEA-SNP) identified gene sets and leading-edge genes enriched (NES ≥ 3) for BRD. Results: In pre-weaned calves, 62 loci and 123 positional candidate genes were associated (P < 1 × 10⁻⁵) in addition to the 12 gene sets and 126 leading-edge genes enriched (NES ≥ 3) for BRD. In post-weaned calves, 181 loci and 185 positional candidate genes were associated (P < 1 × 10⁻⁵), and 63 gene sets and 849 leading-edge genes were enriched (NES ≥ 3) for BRD. Conclusions: These results provide further insight and validation of genomic regions that enhance selection for BRD resistance and for healthier cattle. Full article

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease of 2019 (COVID-19) and has persistently caused infections since its emergence in late 2019. The main protease (Mpro) of SARS-CoV-2 plays a crucial role in its life-cycle; thus, it is an important target for drug development. One of the first virus-specific drugs that has been approved for the treatment of COVID-19 patients is Paxlovid, which contains nirmatrelvir, a covalent inhibitor of Mpro. Screening of inhibitor candidates and specificity studies also rely on efficient substrates and activity assays. Casein is one of the most commonly applied universal substrates that can be used to study a wide range of proteases, including SARS-CoV-2 Mpro. Casein is a known substrate for Mpro in vitro, but the specific casein isoform cleaved by Mpro remained unidentified, and the cleavage sites have yet to be determined. This work studied cleavage of α-, β- and κ-isoforms of bovine casein by SARS-CoV-2 Mpro, using in vitro and in silico approaches. The candidate cleavage sites were predicted in silico based on the protein sequences, and the cleavage positions were identified based on mass spectrometric analysis of cleavage fragments. Based on our results, only β-casein contains cleavage sites for Mpro and thus can be used as its substrate in vitro. The newly identified cleavage site sequences further widen the knowledge about the specificity of SARS-CoV-2 Mpro. Full article

Bovine respiratory disease (BRD) is the most significant disease challenge in the feeder cattle industry in North America. Antimicrobials are commonly administered in BRD cases due to the role of bacterial pathogens. However, reports of antimicrobial resistance (AMR) in these pathogens raise concerns regarding their long-term effectiveness to treat BRD cases. A systematic literature review was conducted to summarize AMR in North American BRD pathogens and determine if changes in AMR prevalence over time could be identified for antimicrobials routinely used for treatment and control of BRD. Generalized linear models were used to test associations between the proportion of resistant isolates for each of the three bacterial agents and antimicrobial agent, isolation year, and timing of sample collection. The antimicrobial agent and timing of sample collection were significantly associated with the proportion of antimicrobial resistant isolates, with increased probability of resistance to tulathromycin seen in Mannheimia haemolytica (24.08%) and Histophilus somni (8.19%) and increased resistance to tildipirosin in Pasteurella multocida (21.48%), while samples collected at arrival demonstrated a lower proportions of resistant bacteria. Trends over time could not be evaluated due to the limited number of published studies. These findings highlight the differences in AMR seen between antimicrobials, BRD pathogens, and sample types and emphasize the need for continued AMR surveillance. Full article

Field-based diagnostic technologies which aid in the early detection of bovine respiratory disease (BRD) are of great need, given the rising attention related to animal welfare and antimicrobial stewardship. This induced BRD study followed 12 Holstein calves through pre-challenge (day 1–3) and post-challenge (day 6–13) periods with daily sampling of nasal secretions with nasal swabs and expired air with air collection bags for determination of BRD status by use of an electronic nose (eNose). Animals were challenged with bovine herpes virus-1 (BHV-1) on day 3 following sample collection and Mannheimia haemolytica on day 5. Results demonstrated a high degree of accuracy for the eNose in correctly classifying pre-challenge samples for nasal swabs (93.5%) and expired air (96.8%). Post-challenge correct classification by the eNose was 97.8% for nasal swabs and 72.5% for expired air samples. Logistical regression was used to determine the probability of agreement between eNose classification and actual animal BRD status by study day. The largest discrepancy between nasal swab and expired air samples fell on days 6 and 7, immediately following the bacterial challenge. The eNose demonstrated potential as a field-based diagnostic tool for the detection of BRD with nasal swabs as the optimal sample type. Full article

Serum beta-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFAs) are biomarkers of situations of negative energetic balance in bovine. However, knowledge about their possible measurement and use in saliva is limited. In this report, two commercially available methods for the measurement of BHB and NEFAs were validated for use in bovine saliva. Both methods showed good precision and accuracy. The BHB concentrations were correlated between the saliva and the serum, but not the NEFA concentrations. The cows with hyperketonemia (n = 17) had increased salivary BHB compared to the cows with no clinical signs and no hyperketonemia (n = 34) and those with clinical signs of metritis (n = 17). The salivary NEFA concentration increased in newborn calves (n = 10) on days 1 and 2 of life compared to the day of birth before colostrum intake. The calves with symptomatic bovine respiratory disease complex (BRD, n = 7) showed higher salivary NEFA concentrations than those without clinical symptoms (n = 6). Thus, BHB and NEFAs can be reliably measured in bovine saliva using easily automatable colorimetric methods. Salivary BHB increased in hyperketonemia and could be a potential biomarker of this condition. Further studies should be undertaken to clarify the mechanism and possible use of salivary NEFAs as biomarkers. Full article

Bovine enterovirus (BEV) infection is one of the important infectious diseases that cause digestive and respiratory symptoms in cattle, posing a significant threat to the cattle industry. Currently, no vaccines or therapeutic drugs are available for this disease. In our study, we utilized a mouse model to investigate the effects of BEV infection on the gut microbiota and examine the therapeutic potential of magnolol (Mag), a polyphenolic bioactive substance, in terms of BEV infection. BEV infection significantly altered the microbiota composition, where the abundance of some beneficial bacteria, such as Lactobacillaceae and Lactobacillus, was markedly reduced. Mag effectively inhibited BEV infection in vivo. Upon BEV infection, Mag treatment reduced the α-diversity of the microbiota, with statistically significant differences on day 3 post-infection compared to the Mag-untreated group. More interestingly, Mag treatment significantly reversed the effect of BEV infection on the Lactobacillaceae and Lactobacillus abundance, indicating that Mag positively regulates beneficial bacteria. The fecal microbiota transplantation (FMT) experiment demonstrated that feces from Mag-treated mice significantly decreased the virus loads in the small intestine samples of BEV-infected mice. These findings demonstrate the interaction between BEV infection and the gut microbiota and highlight the important regulatory role of the gut microbiota in Mag’s anti-BEV effects, opening up a new avenue for preventing and controlling BEV infection via targeted modulation of the gut microbiota. Full article

There are few studies on how dairy × beef crossbred calves perform during the pre-weaning phase compared to dairy calves. This observational study evaluated birth weight, average daily gain (ADG), and disease occurrence in Angus × Holstein (Ang × Hol) crossbred and Holstein calves reared under the same conditions on a commercial dairy farm. Retrospective data from 379 calves (290 Holstein females; 89 Ang × Hol crossbreds: 46 males, 43 females) born between January 2022 and August 2023 were analyzed. Variables included dam parity, calving type, birth weight, colostrum Brix levels, serum total protein (STP), mortality, disease occurrence, ADG, and weaning weight. Statistical analysis used linear and logistic regression models. Ang × Hol male calves had higher odds of assisted calving. Male and female Ang × Hol calves had greater birth weights than Holstein calves, with males being the heaviest. No differences in STP were observed. Ang × Hol calves (both sexes) showed higher ADG than Holsteins but did not differ from each other. Holstein calves had higher odds of diarrhea (OR: 2.95, 95% CI: 1.63–5.35), while Bovine Respiratory Disease (BRD) incidence was similar across groups. Overall, Ang × Hol crossbred calves demonstrated superior growth and lower diarrhea risk under the same management conditions. Full article

Timely, accurate, and reliable laboratory tools are important for antimicrobial stewardship (AMS) in food animal production. The objectives of this study were to (1) identify factors that influence live animal respiratory sample collection for laboratory testing and (2) describe the potential for integration of laboratory testing of samples from live animals into an AMS strategy for bovine respiratory disease (BRD) management in Canadian feedlots. Utilizing focused ethnography, virtual key informant interviews were conducted with eight feedlot veterinarians from Alberta, Ontario, and Saskatchewan, Canada. Thematic analysis revealed four themes: (1) lived experience of feedlot veterinarians with laboratory testing for BRD pathogens and antimicrobial resistance (AMR), (2) evidence-informed BRD management that integrates multiple data sources and their components, (3) organizational factors that affect the uptake and use of laboratory tests, and (4) the role of laboratory testing to support AMS in BRD management. While sample collection and laboratory testing are commonly used for BRD and AMR research and surveillance, they are not routinely applied in everyday BRD management. Veterinarians identified key challenges with laboratory testing, including turnaround time, the need for clear benefits, practical implementation, and effective communication with feedlot managers. Laboratory testing must provide valuable, actionable insights to encourage its adoption in Canadian feedlot operations. If successful, such testing could support AMS and be used to justify antimicrobial use if this were to become a regulatory or market requirement. Full article

The ovine respiratory complex significantly affects lamb welfare and production efficiency, necessitating accurate diagnostic methods for pulmonary lesions. This study explores the relationship between clinical scoring, auscultation, ultrasonography, and macroscopic post-mortem evaluation to assess respiratory disease in 111 lambs. A standardized clinical scoring system, adapted from bovine models, evaluated ocular and nasal discharge, head tilt, cough, and rectal temperature. Auscultation categorized pulmonary sounds, while ultrasonography identified lung abnormalities, including B-lines, consolidations, pleural effusion, and abscesses. Macroscopic post-mortem examinations confirmed lesion extent. Kendall–Tau-B correlation coefficient analysis revealed significant associations between the methods (p < 0.01), with a high correlation between auscultation and clinical scoring τ of 0.634 (95% CI: 0.489 to 0.765), auscultation and ultrasonography τ of 0.611 (95% CI: 0.500 to 0.710), and ultrasonography and post-mortem findings τ 0.608 (95% CI: 0.460 to 0.731). While auscultation and clinical scoring provided useful insights, ultrasonography exhibited superior sensitivity in detecting subclinical and early-stage lesions, aligning closely with post-mortem evaluations. These findings emphasize ultrasonography as an effective tool for diagnosing respiratory disease in lambs, improving diagnostic accuracy and enabling timely interventions to mitigate disease impact and reduce antimicrobial use. Full article

Accurate prognosis at first treatment for bovine respiratory disease (BRD) is essential for timely interventions and management decisions. This cross-sectional observational study evaluated 819 commercial beef feedyard cattle at chute-side for first BRD treatment. Logistic regression models examined potential associations between two outcomes—first treatment failure (requiring additional treatment) and unfinished treatment (due to mortality or culling)—and several explanatory variables, including sex, days on feed, bodyweight, breed, pulse oximetry, lung auscultation scores, and ultrasound lung scores (ULS) measured in the caudo-dorsal lung region. Animals that ultimately did not finish treatment were significantly more likely to present a ULS of 5 (74%) compared with those scored 1–4 (18–38%). Similarly, cattle with a ULS of 5 had a much higher probability of first treatment failure (74%) than those with scores of 1–3 (35–41%). Moreover, three or more B-lines in the ultrasound image or a “moth sign” finding were both strongly associated with increased probability of negative outcomes. These results highlight key ultrasound-based and demographic factors that serve as practical prognostic indicators for cattle at the onset of BRD treatment. Full article