Monkeypox virus (MPV), an endemic pathogen in Africa, shares clinical similarities with smallpox. Recent reports indicate a concerning increase in the number of MPV cases detected outside its endemic region, highlighting the emergence of a multi-country outbreak. Given the importance of the cell surface-binding protein E8L in facilitating viral attachment to host cells, this study aimed to identify potential small interfering RNAs (siRNAs) capable of silencing E8L and thereby serving as a basis for therapeutic development. siRNAs have emerged as promising candidates for genetic therapies and antiviral and antibacterial treatments. In this investigation, we employed computational assays, including GC content analysis, binding free energy assessment, folding properties evaluation, melting temperature determination, and siRNA efficacy prediction. Our comprehensive analysis identified five siRNAs with high potential for effectively silencing the cell surface-binding protein of the monkeypox virus. Among these siRNAs, molecular docking revealed that “S8” (Guide-UUAUGGAUCCAAUCACUUGAU, Passenger-CAAGUGAUUGGAUCCAUAAUC) demonstrated the strongest affinity with the human argonaute-2 protein. The siRNA “S8” represents a promising therapeutic target for developing treatments against monkeypox virus infection by specifically silencing the cell surface-binding protein E8L. Our research lays the foundation for future endeavors in genome-level therapies. It can potentially create chemically produced RNA molecules as effective antiviral drugs targeting Monkeypox virus infection. These findings contribute to advancing therapeutic strategies and offer new avenues for combating the spread of MPV, particularly in regions affected by the multi-country outbreak.

中文翻译：

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免疫信息和分子对接方法：siRNA 预测沉默猴痘病毒细胞表面结合蛋白

猴痘病毒（MPV）是非洲的一种地方性病原体，其临床与天花有相似之处。最近的报告表明，在流行区以外发现的 MPV 病例数量出现令人担忧的增加，突显了多国疫情的出现。鉴于细胞表面结合蛋白 E8L 在促进病毒附着于宿主细胞方面的重要性，本研究旨在鉴定能够沉默 E8L 的潜在小干扰 RNA (siRNA)，从而作为治疗开发的基础。siRNA 已成为基因治疗、抗病毒和抗菌治疗的有希望的候选者。在这项研究中，我们采用了计算分析，包括 GC 含量分析、结合自由能评估、折叠特性评估、解链温度测定和 siRNA 功效预测。我们的综合分析确定了 5 种 siRNA，它们非常有可能有效沉默猴痘病毒的细胞表面结合蛋白。在这些siRNA中，分子对接显示“S8”（Guide-UUAUGGAUCCAAUCACUUGAU，Passenger-CAAGUGAUUGGAUCCAAUAAUC）与人argonaute-2蛋白的亲和力最强。siRNA“S8”代表了一个有前途的治疗靶点，可通过特异性沉默细胞表面结合蛋白E8L来开发针对猴痘病毒感染的治疗方法。我们的研究为未来基因组水平疗法的努力奠定了基础。它有可能产生化学产生的 RNA 分子，作为针对猴痘病毒感染的有效抗病毒药物。这些发现有助于推进治疗策略，并为遏制 MPV 传播提供新途径，特别是在受多国疫情影响的地区。