Hasib F M Yasir, Islam Md Shafiqul
Department of Pathology and Parasitology, Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh.
Vet Med Sci. 2025 Jul;11(4):e70437. doi: 10.1002/vms3.70437.
Lumpy skin disease virus (LSDV) is the etiological agent of lumpy skin disease (LSD), predominantly afflicting cattle populations and posing significant economic implications to the livestock industry. Despite the comprehensive genome sequencing of LSDV, several hypothetical genes with unknown functions remain, potentially playing pivotal roles in disease pathogenesis and serving as targets for drug discovery. This study aimed to explore the LSDV004 gene by predicting its key properties, structure, functions and potential inhibitors using bioinformatic tools. Physiochemical analysis using ExPASy ProtParam indicates LSDV004 is a stable protein with an instability index below 40, suggesting structural stability. Secondary structure analysis via SOPMA identifies the random coil as the predominant structural element, covering 50.88% of residues, followed by extended strands (36.84%). The tertiary structure predicted and refined using SWISS-MODEL and GalaxyRefine respectively, > 90% of residues in the favoured region of the Ramachandran plot, according to PROCHECK validation. Functional prediction highlights structural similarities with the Swinepox virus C2 and suggests potential involvement in pathways such as negative regulation of gene expression, as indicated by gene ontology (GO) analysis using I-TASSER. Moreover, the GO analysis indicates functional similarity with anti-apoptotic protein Bcl-2-like protein 1 (PDB ID: 1LXL). Molecular docking studies with HDOCK reveal pelcitoclax as exhibiting better docking characteristics compared to other Bcl-2 inhibitors. However, it's important to note that these predictions require validation through wet laboratory experiments to confirm the LSV004 protein's structural, functional and inhibitory properties. These findings suggest LSDV004's role in LSD pathogenesis and its potential as a drug target and also highlight areas for further experimental studies to confirm its function, supporting efforts toward effective treatments and control.
结节性皮肤病病毒（LSDV）是结节性皮肤病（LSD）的病原体，主要感染牛群，给畜牧业带来重大经济影响。尽管已对LSDV进行了全面的基因组测序，但仍有几个功能未知的假设基因，它们可能在疾病发病机制中起关键作用，并可作为药物研发的靶点。本研究旨在利用生物信息学工具预测LSDV004基因的关键特性、结构、功能和潜在抑制剂，从而对该基因进行探索。使用ExPASy ProtParam进行的理化分析表明，LSDV004是一种稳定蛋白，其不稳定指数低于40，表明结构稳定。通过SOPMA进行的二级结构分析确定无规卷曲是主要的结构元件，占残基的50.88%，其次是延伸链（36.84%）。分别使用SWISS-MODEL和GalaxyRefine预测和优化三级结构，根据PROCHECK验证，超过90%的残基位于拉氏图的有利区域。功能预测突出了与猪痘病毒C2的结构相似性，并表明可能参与基因表达的负调控等途径，这是使用I-TASSER进行的基因本体（GO）分析所表明的。此外，GO分析表明与抗凋亡蛋白Bcl-2样蛋白1（PDB ID：1LXL）功能相似。与HDOCK进行的分子对接研究表明，与其他Bcl-2抑制剂相比，pelcitoclax具有更好的对接特性。然而，需要注意的是，这些预测需要通过湿实验室实验进行验证，以确认LSV004蛋白的结构、功能和抑制特性。这些发现表明LSDV004在LSD发病机制中的作用及其作为药物靶点的潜力，也突出了需要进一步进行实验研究以确认其功能的领域，为有效治疗和控制提供支持。
