Molecules. 2025 Feb 8;30(4):790. doi: 10.3390/molecules30040790.

ABSTRACT

Avian coccidiosis, caused by protozoan parasites of the genus Eimeria, poses a major threat to the poultry industry worldwide, leading to severe economic losses through reduced growth rates, poor feed efficiency, and increased mortality. Although the conventional management of this disease has relied on anticoccidial drugs, the overwhelming use of these agents has led to the rapid emergence and spread of drug-resistant Eimeria isolates, highlighting the urgent need for novel therapeutic approaches. This study employed computational approaches to identify novel inhibitors targeting Eimeria tenella prolyl-tRNA synthetase (EtPRS). Based on the virtual screening of a library of 3045 natural compounds, 42 high-confidence inhibitors were identified. Three compounds, including Chelidonine, Bicuculline, and Guggulsterone, demonstrated strong and selective binding to EtPRS through stable interactions within the active site. ADMET predictions revealed favorable safety profiles, while molecular dynamic simulations confirmed binding stability. Overall, this research established a solid framework for the development of effective anticoccidial agents targeting PRS, contributing to the advancement of therapeutic strategies for combating parasitic infections in the poultry industry.

PMID:40005102 | PMC:PMC11858595 | DOI:10.3390/molecules30040790

Sci China Life Sci. 2025 Feb 20. doi: 10.1007/s11427-024-2856-y. Online ahead of print.

ABSTRACT

Identification of host factors that play a key role in viral replication is of great importance for antiviral development. Metabotropic glutamate receptor subtype 2 (mGluR2) is the receptor to trigger clathrin-mediated endocytosis (CME), the major pathway by which influenza virus enters cells. However, other host factors almost certainly involved in the influenza virus CME are largely unknown. Here, we found that the four-transmembrane protein claudin-11 plays an integral part in influenza virus CME. Claudin-11 promotes the dissociation of KCa1.1 (potassium calcium-activated channel subfamily M alpha 1) from mGluR2 and, together with mGluR2, is internalized in virus-containing clathrin-coated pits (CCPs), where it regulates the depolymerization of polymerized F-actin, allowing the CCPs to mature. Importantly, over 60% of claudin-11-silenced mice survived infection with a lethal influenza virus. Our findings advance the understanding of influenza virus infection and provide a promising strategy for the development of host-based antiviral drugs.

PMID:39985647 | DOI:10.1007/s11427-024-2856-y

Lancet Infect Dis. 2025 Feb 17:S1473-3099(25)00068-4. doi: 10.1016/S1473-3099(25)00068-4. Online ahead of print.

NO ABSTRACT

PMID:39978373 | DOI:10.1016/S1473-3099(25)00068-4

BMC Vet Res. 2025 Feb 12;21(1):62. doi: 10.1186/s12917-025-04508-2.

ABSTRACT

BACKGROUND: Infectious diseases including Newcastle disease (ND) impair poultry productivity and represent a significant burden to sustainable agriculture in Nigeria. This study aimed to investigate the active circulation and seroprevalence of Newcastle disease virus (NDV) caused by virulent forms of avian paramyxovirus type-1 (APMV-1) in poultry at live bird markets (LBMs) across Nigeria.

METHODS: A cross-sectional study of 18 LBMs was conducted within three states in Nigeria (Kano, Oyo, and Abuja). Paired swab and tissue samples (n = 413) were collected from birds on FTA cards and tested for APMV-1 using real-time reverse transcription polymerase chain reaction (rRT-PCR). A subset of rRT-PCR-positive samples were selected for whole genome sequencing based on the originating species (chicken, duck, geese), date, and market location to provide a broad range of isolates for characterisation. Blood samples (n = 405) were also collected from birds and the seroprevalence of APMV-1 antibodies was measured using an enzyme-linked immunosorbent assay (ELISA).

RESULTS: APMV-1 RNA was detected in 21.5% (89/413) of samples from LBMs by rRT-PCR. At least one APMV-1 positive sample was detected in 55.6% (10/18) of LBMs. The largest proportion of APMV-1-positive markets was in Kano (83.3%, 5/6), whereas the lowest was in Oyo (16.7%, 1/6). Assessment of genetic data demonstrated that genotype XIV.2 APMV-1 was circulating within Nigeria with the viruses detected clustering closely with other Nigerian isolates described previously. The seroprevalence of APMV-1 in birds was 45.9% (186/405) and 94.4% (17/18) of LBMs had at least one APMV-1 seropositive sample (i.e., with at least one APMV-1-antibody-positive bird). The LBMs in Kano had the lowest seroprevalence (88.3%, 5/6).

CONCLUSIONS: This study demonstrated that APMV-1 continues to circulate in LBMs in Nigeria. LBM traders, poultry producers, and related industry and policy stakeholders should be aware of the occurrence of APMV-1 and how ND may negatively impact upon poultry production and the livelihoods of poultry farmers and LBM traders. Training initiatives aimed at improving the knowledge of APMV-1 infection and improvements in biosecurity practises and the role of disease mitigation through vaccination are required to reduce the impact of this threat to food security.

PMID:39939962 | PMC:PMC11817539 | DOI:10.1186/s12917-025-04508-2

Nat Commun. 2025 Jan 20;16(1):861. doi: 10.1038/s41467-024-55737-2.

ABSTRACT

The World Health Organization describes brucellosis as one of the world's leading zoonotic diseases, with the Middle East a global hotspot. Brucella melitensis is endemic among livestock populations in the region, with zoonotic transmission occurring via consumption of raw milk, amongst other routes. Control is largely via vaccination of small ruminant and cattle populations. Due to sociocultural and religious influences camel milk (camelus dromedarius) is widely consumed raw, while milk from other livestock species is largely boiled. To investigate the potential public health impact of Brucella in camels we conduct a cross-sectional study in southern Jordan including 227 herds and 202 livestock-owning households. Here we show daily consumption of raw camel milk is associated with Brucella seropositive status among the study population, OR_adj 2.19 (95%CI 1.23-3.94) on multivariable analysis, highlighting the need for socioculturally appropriate control measures; targeted interventions among the camel reservoir being crucial for effective control.

PMID:39833143 | PMC:PMC11756418 | DOI:10.1038/s41467-024-55737-2

Adv Sci (Weinh). 2025 Jan 10:e2414651. doi: 10.1002/advs.202414651. Online ahead of print.

ABSTRACT

To bolster the capacity for managing potential infectious diseases in the future, it is critical to develop specific antiviral drugs that can be rapidly designed and delivered precisely. Herein, a CRISPR/Cas13d system for broad-spectrum targeting of influenza A virus (IAV) from human, avian, and swine sources is designed, incorporating Cas13d mRNA and a tandem CRISPR RNA (crRNA) specific for the highly conserved regions of viral polymerase acidic (PA), nucleoprotein (NP), and matrix (M) gene segments, respectively. Given that the virus targets cells with specific receptors but is not limited to a single organ, a Susceptible Cell Selective Delivery (SCSD) system is developed by modifying a lipid nanoparticle with a peptide mimicking the function of the hemagglutinin of influenza virus to target sialic acid receptors. The SCSD system can precisely deliver an all-RNA-based CRISPR/Cas13d system into potentially infected cells. This drug is shown to reduce the viral load in the lungs by 2.37 log₁₀ TCID₅₀ mL^-1 and protect 100% of mice from lethal influenza infection. The SCSD-based CRISPR/Cas13d system shows promise for the flexible and efficient therapy of infections caused by rapidly evolving and novel viruses.

PMID:39792803 | DOI:10.1002/advs.202414651

Nat Commun. 2025 Jan 9;16(1):432. doi: 10.1038/s41467-024-55193-y.

ABSTRACT

Influenza remains a persistent global health challenge, largely due to the virus' continuous antigenic drift and occasional shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanobodies, with their unique characteristics and binding capacity, offer a promising avenue to identify such epitopes. Here, we isolate and purify a hemagglutinin (HA)-specific nanobody that recognizes an H7 subtype of influenza A virus. The nanobody, named E10, exhibits broad-spectrum binding, cross-group neutralization and in vivo protection across various influenza A subtypes. Through phage display and in vitro characterization, we demonstrate that E10 specifically targets an epitope on HA head which is part of the conserved lateral patch and is highly immunodominant upon H7 infection. Importantly, immunization with a peptide including the E10 epitope elicits cross-reactive antibodies and mediates partial protection from lethal viral challenge. Our data highlights the potential of E10 and its associated epitope as a candidate for future influenza prevention strategies.

PMID:39788944 | PMC:PMC11718266 | DOI:10.1038/s41467-024-55193-y

PLoS Biol. 2024 Nov 12;22(11):e3002916. doi: 10.1371/journal.pbio.3002916. eCollection 2024 Nov.

ABSTRACT

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple nonhuman mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here, we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine virus, and we show that a mutation present in some recent H5 HAs causes a large antigenic change. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

PMID:39531474 | PMC:PMC11584116 | DOI:10.1371/journal.pbio.3002916

Viruses. 2024 Oct 9;16(10):1585. doi: 10.3390/v16101585.

ABSTRACT

Pigeon paramyxovirus serotype 1 (PPMV-1), an antigenic and host variant of avian paramyxovirus Newcastle disease virus (NDV), primarily originating from racing pigeons, has become a global panzootic. Egypt uses both inactivated PPMV-1 and conventional NDV vaccines to protect pigeons from disease and mortality. However, the impact of prevalent strains and the effectiveness of available vaccines in pigeons in Egypt are unclear. This study investigates the virulence of PPMV-1 (Pigeon/Egypt/Sharkia-19/2015/KX580988) and evaluates available paramyxovirus vaccines in protecting pigeons against a PPMV-1 challenge. Ten-day-old specific-pathogen-free (SPF) embryonated chicken eggs infected with this strain exhibited a mean death time (MDT) of 86.4 ± 5.88 h. The intracerebral pathogenicity index (ICPI) in day-old chickens was 0.8, while pigeons experienced an ICPI of 0.96 and an intravenous pathogenicity index (IVPI) of 2.11. These findings classify the strain as virulent and velogenic. Experimental infection of pigeons with this PPMV-1 strain at 10⁶ EID₅₀/0.1 mL resulted in a 62.5% mortality rate, displaying nervous and enteric distress. The virus caused extensive lesions in visceral organs, with strong immunohistochemistry signals in all examined organs, indicating the systemic spread of the virus concurrent to its neurotropic and viscerotropic tropism. Furthermore, vaccination using an inactivated PPMV-1 and live NDV LaSota vaccine regimen protected 100% of pigeons against mortality, while with a single NDV LaSota vaccine, it was 62.5%. The PPMV alone or combined with NDV LaSota induced protective levels of haemagglutination inhibition (HI) antibody titres and reduced virus shedding from buccal and cloacal cavities. Based on generalised linear gamma model analysis, both PPMV-1 and NDV LaSota are antigenically comparable by HI. These findings suggest that using both inactivated PPMV-1 (G-VI) and live attenuated NDV (LaSota) vaccines is an effective prophylactic regimen for preventing and controlling PPMV-1 and NDV in pigeons, thereby reducing the risk of interspecies transmission.

PMID:39459921 | PMC:PMC11512342 | DOI:10.3390/v16101585

Vet Microbiol. 2024 Nov;298:110270. doi: 10.1016/j.vetmic.2024.110270. Epub 2024 Sep 28.

ABSTRACT

Orthoflaviviruses are single-stranded RNA viruses characterized by highly efficient self-amplification of RNA in host cells, which makes them attractive vehicles for vaccines. Numerous preclinical and clinical studies have demonstrated the efficacy and safety of orthoflavivirus replicon vectors for vaccine development. In this study, we constructed Tembusu virus (TMUV) replicon-based single-round infectious particles (SRIPs) as vaccine development platform. To evaluate the potential of TMUV SRIPs as vaccines, we generated SRIPs that express the heterologous Fowl adenovirus 4 (FAdV-4) fiber2 protein and fiber2 head domain, named TMUVRP-fiber2 and TMUVRP-fiber2H, respectively. To assess the immunogenicity of the TMUV SRIPs, SPF chicks were intramuscularly inoculated twice. Our results showed that the TMUVRP-fiber2 vaccines elicited high levels of neutralizing antibodies. Challenge experiments showed that TMUVRP-fiber2 provided full protection against virulent FAdV-4 and significantly reduced viral shedding. Moreover, the immunogenicity of TMUVRP-fiber2H was significantly lower than that of TMUVRP-fiber2, which was reflected in the neutralizing antibody titer, survival rate, and virus shedding after challenge. Therefore, our results suggested that TMUV SRIPs are a promising novel platform for the development of vaccines for existing and emerging poultry diseases.

PMID:39357096 | DOI:10.1016/j.vetmic.2024.110270