High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ's role in augmenting the sensitivity of the IFN-ß pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ's effectiveness.

TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro.

TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies.

Antiviral Effect of Manganese against Foot-and-Mouth Disease Virus Both in PK15 Cells and Mice.

Foot-and-mouth disease (FMD) is an acute contagious disease of cloven-hoofed animals such as cattle, pigs, and sheep. Current emergency FMD vaccines are of limited use for early protection because their protective effect starts 7 days after vaccination. Therefore, antiviral drugs or additives are used to rapidly stop the spread of the virus during FMD outbreaks. Manganese (Mn2+) was recently found to be an important substance necessary for the host to protect against DNA viruses. However, its antiviral effect against RNA viruses remains unknown. In this study, we found that Mn2+ has antiviral effects on the FMD virus (FMDV) both in PK15 cells and mice. The inhibitory effect of Mn2+ on FMDV involves NF-κB activation and up-regulation of interferon-stimulated genes. Animal experiments showed that Mn2+ can be highly effective in protecting C57BL/6N mice from being infected with FMDV. Overall, we suggest Mn2+ as an effective antiviral additive for controlling FMDV infection.

Understanding the research advances on lumpy skin disease: A comprehensive literature review of experimental evidence.

Lumpy skin disease is caused by lumpy skin disease virus (LSDV), which can induce cattle with high fever and extensive nodules on the mucosa or the scarfskin, seriously influencing the cattle industry development and international import and export trade. Since 2013, the disease has spread rapidly and widely throughout the Russia and Asia. In the past few decades, progress has been made in the study of LSDV. It is mainly transmitted by blood-sucking insects, and various modes of transmission with distinct seasonality. Figuring out how the virus spreads will help eradicate LSDV at its source. In the event of an outbreak, selecting the most effective vaccine to block and eliminate the threat posed by LSDV in a timely manner is the main choice for farmers and authorities. At present, a variety of vaccines for LSDV have been developed. The available vaccine products vary in quality, protection rate, safety and side effects. Early detection of LSDV can help reduce the cost of disease. In addition, because LSDV has a huge genome, it is currently also used as a vaccine carrier, forming a new complex with other viral genes through homologous recombination. The vaccine prepared based on this can have a certain preventive effect on many kinds of diseases. Clinical detection of disease including nucleic acid and antigen level. Each method varies in convenience, accuracy, cost, time and complexity of equipment. This article reviews our current understanding of the mode of transmission of LSDV and advances in vaccine types and detection methods, providing a background for further research into various aspects of LSDV in the future.

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems.

Rabies is a lethal zoonotic disease caused by lyssaviruses, such as rabies virus (RABV), that results in nearly 100% mortality once clinical symptoms appear. There are no curable drugs available yet. RABV contains five structural proteins that play an important role in viral replication, transcription, infection, and immune escape mechanisms. In the past decade, progress has been made in research on the pathogenicity of RABV, which plays an important role in the creation of new recombinant RABV vaccines by reverse genetic manipulation. Here, we review the latest advances on the interaction between RABV proteins in the infected host and the applied development of rabies vaccines by using a fully operational RABV reverse genetics system. This article provides a background for more in-depth research on the pathogenic mechanism of RABV and the development of therapeutic drugs and new biologics.

Research progress on live attenuated vaccine against African swine fever virus.

African swine fever (ASF) is an acute, hemorrhagic and severe infectious disease caused by African swine fever virus (ASFV) in domestic pigs and various wild boars, with a mortality rate up to 100%. ASF was first discovered in 1921 in Kenya. ASFV has a large genome and complex immune escape mechanism creating difficulties in the production of vaccines. Recently, remarkable advances have been made in vaccine development all over the world especially in live-attenuated vaccine. This article aims to review the research progress of ASF attenuated live vaccines in order to provide a reference for the development of vaccines for this disease.