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RNA viruses pose a persistent global threat due to their high mutation rates, zoonotic potential, and rapid adaptability. Emergence events have risen steadily, as demonstrated by major outbreaks caused by Influenza A, Ebola, Zika, and Chikungunya viruses, followed by the coronavirus epidemics of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and culminating in the COVID-19 pandemic. These characteristics frequently compromise the durability of existing vaccines and antiviral therapies, highlighting the urgent need for new antiviral agents. Alkaloids, a structurally diverse class of nitrogen-containing natural compounds, have gained attention for their ability to interfere with multiple stages of the viral life cycle, including entry, replication, protein synthesis, and host immune modulation. To our knowledge, this review compiles all currently reported alkaloids with antiviral activity against RNA viruses and summarizes their proposed mechanisms of action, distinguishing evidence from in vitro, in vivo, and in silico studies. Quaternary alkaloids are discussed separately because their permanent ionic charge enables distinctive interactions with membranes and host pathways. Although many findings are promising, clinical translation remains limited by incomplete mechanistic validation, scarce in vivo data, suboptimal bioavailability, narrow therapeutic windows, and inconsistent experimental methodologies. To advance the field, future research should prioritize RT-qPCR–based antiviral evaluation to accurately quantify viral replication, incorporate mechanistic assays to clarify modes of action, apply structure–activity relationship (SAR) approaches for rational optimization, and expand in vivo pharmacokinetic and efficacy studies to assess therapeutic feasibility. Overall, alkaloids represent a promising yet underdeveloped reservoir for next-generation antiviral discovery against rapidly evolving RNA viruses.

Abstract Background Idiopathic pulmonary fibrosis (IPF) affects West Highland white terriers (WHWTs). Osteopontin (SPP1) and fibronectin (FN1) are associated with human IPF and are overexpressed by bronchoalveolar lavage fluid (BALF) macrophages in dogs with IPF. Objective To investigate the value of these proteins as biomarkers of IPF. Animals West Highland white terriers (WHWTs) with IPF, control WHWTs, and terriers. Methods Cross-sectional observational study. Immunohistochemistry was used to localize SPP1 and FN1 in lung tissue. Serum and BALF SPP1 and FN1 concentrations were measured using canine ELISA kits and compared between groups. Results Osteopontin stained ciliated epithelial cells, smooth muscular cells, and macrophages of all included dogs, and type-II pneumocytes and extracellular matrix of all 12 diseased WHWTs, 4/6 control WHWTs, and none of the 3 terriers. Osteopontin serum concentration was higher in diseased WHWTs (n = 22; 2.15 ng/mL [0.74-5.30]) compared with control WHWTs (n = 13; 0.63 ng/mL [0.41-1.63]; P = .005) and terriers (n = 15; 0.31 ng/mL [0.19-0.51]; P < .0001), and in control WHWTs compared with terriers (P = .005). Osteopontin BALF concentrations were higher in diseased (0.27 ng/mL [0.14-0.43]) and control WHWTs (0.25 ng/mL [0.14-0.40]), compared with terriers (0.02 ng/mL [0.01-0.08]; P < .0001 and P = .003, respectively). Fibronectin (FN1) serum concentrations were lower in diseased dogs (1.03 ng/mL [0.35-1.48]) and control WHWTs (0.61 ng/mL [0.24-0.65]) compared with terriers (2.72 ng/mL [0.15-5.21]; P < .0001 and P = .0001, respectively). There was no difference in FN1 immunostaining and FN1 BALF concentrations between groups. Conclusions Results suggest that SPP1 is involved in pathogenesis of IPF and could predispose that breed to the disease. Osteopontin serum concentration could serve as a diagnostic biomarker of IPF.

The aim of this study is to determine to what extent the addition of chitinase to black soldier fly (BSF) larval meal enriched or not with long-chain PUFA (LC-PUFA) could improve growth, protein digestion processes and gut microbial composition in Nile tilapia. Two different types of BSF meal were produced, in which larvae were reared on substrates formulated with vegetable culture substrate (VGS) or marine fish offal substrate (FOS). The BSF raised on VGS was enriched in α-linolenic acid (ALA), while that raised on FOS was enriched in ALA + EPA + DHA. Six BSF-based diets, enriched or not with chitinase, were formulated and compared with a control diet based on fishmeal and fish oil (FMFO). Two doses (D) of chitinase from Aspergillus niger (2 g and 5 g/kg feed) were added to the BSF larval diets (VGD0 and FOD0) to obtain four additional diets: VGD2, VGD5, FOD2 and FOD5. After 53 d of feeding, results showed that the BSF/FOS-based diets induced feed utilisation, protein efficiency and digestibility, as well as growth comparable to the FMFO control diet, but better than the BSF/VGS-based diets. The supplementation of chitinase to BSF/FOS increased in fish intestine the relative abundance of beneficial microbiota such as those of the Bacillaceae family. The results showed that LC-PUFA-enriched BSF meal associated with chitinase could be used as an effective alternative to fishmeal in order to improve protein digestion processes, beneficial microbiota and ultimately fish growth rate.

Krüppel-associated box (KRAB)-associated protein 1 (KAP1), also known as TRIM28 due to its tripartite motif (TRIM) domain, is a member of the transcription intermediary factor 1 (TIF1) family. Since its discovery in 1996, KAP1 has been widely studied as a scaffold protein involved in histone methylation, heterochromatin formation, and genome maintenance. Its function and stability are dynamically regulated by post-translational modifications (PTMs), including phosphorylation, SUMOylation, and acetylation. In addition, KAP1 serves as a signal transducer via its SUMO/ubiquitin E3 ligase activity. This review summarizes current advances in understanding the roles of KAP1 in regulating retroviruses (RVs), herpesviruses, and emerging respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV), with a particular focus on the interplay between its structural domains and physiological functions. Recent findings on human immunodeficiency virus (HIV) are highlighted to address ongoing mechanistic controversies, particularly those involving KAP1-mediated latency control. We further examine novel insights into KAP1’s involvement in other viruses, including hepatitis B virus (HBV), porcine reproductive and respiratory syndrome virus (PRRSV), and African swine fever virus (ASFV). as well as its emerging regulatory roles in host innate immune responses through PTM-mediated modulation of antiviral signaling pathways. Although KAP1 exerts both antiviral and proviral effects, the underlying mechanisms remain incompletely defined, especially in systems where conflicting observations exist for the same pathogen. These discrepancies—reflecting both methodological variation and KAP1’s inherent regulatory complexity—underscore the need for deeper mechanistic insight. Future studies utilizing precise genetic tools and in vivo models will be critical for elucidating the context-specific roles of KAP1 in viral gene regulation and advancing its translational potential.

Identifying the main species of plants from where Ecuadorian stingless bees collect pollen is one of the key objectives of management and conservation improvement for these insects. This study aims to determine the botanical origin of pot-pollen using two barcodes, comparing two methodologies (DNA barcoding versus electron microscopy and morphometric tools) and determine the genus and species of pollen source plants of the main honey-producing stingless bees in Ecuador. As main results, Prockia crucis , Coffea canephora , Miconia nervosa , Miconia notabilis, Laurus nobilis , Cecropia ficifolia , Theobroma sp., Artocarpus sp., Croton sp., Euphorbia sp., Mikania sp., and Ophryosporus sp., were the genera and species with the highest presence in the nests (n = 35) of three genera of stingless bees of two provinces located in different climatic regions inside the continental Ecuador. Plant species richness in both areas was statistically similar (p-value = 0.21). We concluded that floral sources’ molecular identification with the ITS2 region had a higher number of genera and species detected, than the rbcL gene and microscopy tools, for the Ecuadorian landscapes. We confirmed that the foraging behavior of Melipona sp., Scaptotrigona sp., and Tetragonisca sp., could include non-native flora (27%, 12/44 identifications) that provide a rich source of pollen. Stingless beekeepers could use this information to create flower calendars and establish a schedule for better management of stingless bees in secondary and modified environments.

Abstract Background In dogs with sinonasal aspergillosis (SNA) the utility of PCR in the diagnosis and monitoring of the disease after treatment has not been assessed. Objectives To evaluate the presence of fungal DNA using quantitative PCR targeting Aspergillus fumigatus (Aspfum) and Aspergillus spp. (PanAsp), and PCR targeting multiple fungal species (PanFun), in samples obtained from nasal cavities of dogs with SNA, other nasal diseases and healthy dogs. Animals Sixty-two dogs including 20 with SNA, 12 with cured SNA (of which 10 are from the SNA group), 20 dogs with Non-SNA nasal disease, and 20 healthy dogs. Methods Prospective cross-sectional study. Aspfum, PanAsp, and PanFun were performed on blindly collected nasal swabs obtained in anesthetized dogs. Results In SNA dogs, Aspfum and PanAsp were positive in 13/20 and 14/20 dogs. In all dogs in the 3 other groups, A. fumigatus DNA was not detected using Aspfum. PanAsp was positive in 3 non-SNA dogs: 1 with cured SNA and 2 with Non-SNA nasal disease. A Ct cut-off value of 33.3 for Aspfum demonstrated 65% sensitivity and 100% specificity. A Ct cut-off value of 34.5 for PanAsp demonstrated 70% sensitivity and 96.2% specificity. PanFun was positive in 16/20, 12/12, 19/20, and 7/20 dogs in the SNA, cured SNA, Non-SNA, and healthy groups, respectively. Conclusion and Clinical Importance Aspfum and PanAsp on blindly collected nasal swabs can be useful for the detection of SNA at diagnosis and at cure, especially when more invasive methods are not available.

Bovine Viral Diarrhea Virus (BVDV) is one of the main pathogens that affects ruminants worldwide, generating significant economic losses. Like other RNA viruses, BVDV is characterized by a high genetic variability, generating the emergence of new variants, and increasing the risk of new outbreaks. The last report on BVDV genotypes in France was in 2008, since which there have been no new information. The goal of this study is to determine the genetic diversity of BVDV strains currently circulating in France. To this aim, samples of cattle were taken from different departments that are part of the main areas of livestock production during the years 2018 to 2020. Using the partial sequence of the 5'UTR region of the viral genome, we identified and classified 145 samples corresponding to Pestivirus A and one sample corresponding to Pestivirus D . For the Pestivirus A samples, the 1e, 1b, 1d, and 1l genotypes, previously described in France, were identified. Next, the 1r and 1s genotypes, not previously described in the country, were detected. In addition, a new genotype was identified and was tentatively assigned as 1x genotype. These results indicate an increase in the genetic diversity of BVDV in France.

Usutu virus (USUV), one of the most neglected Old World encephalitic flaviviruses, causes epizootics among wild and captive birds and sporadic infection in humans. The dynamics of USUV spread and evolution in its natural hosts are unknown. Here, we present the phylogeny and evolutionary history of all available USUV strains, including 77 newly sequenced complete genomes from a variety of host species at a temporal and spatial scaled resolution. The results showed that USUV can be classified into six distinct lineages and that the most recent common ancestor of the recent European epizootics emerged in Africa at least 500 years ago. We demonstrated that USUV was introduced regularly from Africa into Europe in the last 50 years, and the genetic diversity of European lineages is shaped primarily by in situ evolution, while the African lineages have been driven by extensive gene flow. Most of the amino acid changes are deleterious polymorphisms removed by purifying selection, with adaptive evolution restricted to the NS5 gene and several others evolving under episodic directional selection, indicating that the ecological or immunological factors were mostly the key determinants of USUV dispersal and outbreaks. Host-specific mutations have been detected, while the host transition analysis identified mosquitoes as the most likely origin of the common ancestor and birds as the source of the recent European USUV lineages. Our results suggest that the major migratory bird flyways could predict the continental and intercontinental dispersal patterns of USUV and that migratory birds might act as potential long-distance dispersal vehicles. IMPORTANCE Usutu virus (USUV), a mosquito-borne flavivirus of the Japanese encephalitis virus antigenic group, caused massive bird die-offs, mostly in Europe. There is increasing evidence that USUV appears to be pathogenic for humans, becoming a potential public health problem. The emergence of USUV in Europe allows us to understand how an arbovirus spreads, adapts, and evolves in a naive environment. Thus, understanding the epidemiological and evolutionary processes that contribute to the emergence, maintenance, and further spread of viral diseases is the sine qua non to develop and implement surveillance strategies for their control. In this work, we performed an expansive phylogeographic and evolutionary analysis of USUV using all published sequences and those generated during this study. Subsequently, we described the genetic traits, reconstructed the potential pattern of geographic spread between continents/countries of the identified viral lineages and the drivers of viral migration, and traced the origin of outbreaks and transition events between different hosts. Usutu virus (USUV), a mosquito-borne flavivirus of the Japanese encephalitis virus antigenic group, caused massive bird die-offs, mostly in Europe. There is increasing evidence that USUV appears to be pathogenic for humans, becoming a potential public health problem. The emergence of USUV in Europe allows us to understand how an arbovirus spreads, adapts, and evolves in a naive environment. Thus, understanding the epidemiological and evolutionary processes that contribute to the emergence, maintenance, and further spread of viral diseases is the sine qua non to develop and implement surveillance strategies for their control. In this work, we performed an expansive phylogeographic and evolutionary analysis of USUV using all published sequences and those generated during this study. Subsequently, we described the genetic traits, reconstructed the potential pattern of geographic spread between continents/countries of the identified viral lineages and the drivers of viral migration, and traced the origin of outbreaks and transition events between different hosts.

Sinonasal aspergillosis (SNA) is a frequent cause of chronic nasal discharge, predominantly caused by . The infection is typically confined to the nasal cavity and/or frontal sinuses, characterized by superficial mucosal fungal plaques and associated with severe lymphoplasmacytic and neutrophilic inflammation of the mucosa. While Neutrophil Extracellular Traps (NETs) have been demonstrated to restrict fungal hyphal proliferation in animal models, their presence and role in canine SNA remain unexplored. In this study, we quantified the presence of NETs in nasal lavage fluid (NALf) or nasal mucosal biopsies from dogs diagnosed with SNA and healthy controls. To unambiguously detect NETs, we employed three detection techniques. The first method consisted in cell-free DNA detection in NAL. The second method measured myeloperoxidase (MPO)-DNA complexes in NAL by ELISA. The third method aimed to directly identify NETs in nasal biopsies by confocal microscopy and characterize histopathological lesions associated to NETs-enriched areas in corresponding adjacent hematoxylin-eosin tissue sections. Interestingly, we were only able to detect NETs in biological samples of dogs with SNA but not in samples from control dogs. Furthermore, NETs-enriched areas were specifically restricted to the surface of the epithelial barrier, where they surrounded fungal spots. These results suggest that NETs are involved in the inflammatory response occurring in SNA and likely regulate disease progression. Whether they limit the fungal propagation or contribute to the pathogenesis of the disease remains to be determined, before assessing their role as potential therapeutic target.

Bladder outlet obstruction (BOO) may lead to detrusor decompensation through progressive bladder remodeling. Most experimental studies rely on acutely induced BOO in rodents. Since progressive obstruction better reflects the condition, non-lethal models are needed to investigate chronic obstruction pathophysiology and evaluate regenerative therapies. This exploratory study aimed to evaluate (1) a progressive BOO model induced by an artificial urethral sphincter (AUS) in 2 dogs and (2) the systemic administration of autologous adipose-derived mesenchymal stem cells (ADMSCs) after obstruction release. Two intact male dogs underwent progressive BOO through gradual AUS inflation. Longitudinal assessment included telemetric urodynamic monitoring, urethral pressure profilometry, ultrasonography, post-void residual measurement, oxidative stress markers in serial blood samples and serial bladder biopsies for histology, transmission electron microscopy, immunohistochemistry, RT-qPCR and RNA sequencing (CCL2, CCR2, GFAP, VEGF, HGF). After AUS removal, one dog received three intravenous injections of 20 × 106 PKH26-labelled autologous ADMSCs. BOO induced functional changes (increased detrusor pressure and urethral resistance, decreased urinary flow, prolonged voiding). No detrusor decompensation or fibrosis comparable to the human condition developed, encouraging refinement of this model. ADMSCs appeared to reach the bladder wall safely, but any influence on the glutathione redox system and CCL2 protein expression needs to be confirmed.