Shekhar Satyam, Maurya Arvind, Bhattamisra Subrat Kumar, Singh Gireesh Kumar, Garabadu Debapriya
Department of Pharmacy, School of Health Sciences, Central University of South Bihar, Gaya, India.
Department of Pharmacology, School of Health Sciences, Central University of Punjab, Bathinda, India.
Rev Med Virol. 2025 Sep;35(5):e70067. doi: 10.1002/rmv.70067.
The Envelope (E)-protein is a key structural element of enveloped viruses that plays a significant role in host-pathogen interactions, viral growth, and hijacking of host innate immune system. Due to lack of antiviral agents and significant adverse effects and less affordability of vaccines, the E-protein targeted drug development is gaining critical attention among the researchers. The present review explores the structural and genomic diversities of E-protein among animal viruses with special interest to flaviviruses, coronaviruses, and herpesviruses. E-protein's viroporin activity damages host cell membrane and induces inflammation that advances the disease progression. The review also explains the viroporin-mediated NOD-like receptor family pyrin domain-containing 3 (NLRP3), Toll-like receptors (TLRs), nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs), and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-linked cellular mechanisms in virus-mediated inflammation. The E-protein is considered an alternative promising antiviral target as its functional domain is conserved. This review further enlists the natural, and synthetic inhibitors of E-protein in the development of antiviral agents based on computational, in vitro, and in vivo studies. The E-protein's universal conservation ability to fasten to cellular membranes and limited structural data imparts significant challenge to selective drug inhibition. The present review highlights that the E-protein together with multiple viral factors will boost treatment performance while minimising viral resistance. In addition, broad-range inhibitors targeting E-proteins have the potential to produce single treatment solutions in combating viral infections including several viral strains. In conclusion, E-protein targeted drug would be beneficial in developing potential antiviral agents with high drug specificity, and less viral resistance.
包膜（E）蛋白是包膜病毒的关键结构元件，在宿主与病原体的相互作用、病毒生长以及劫持宿主先天免疫系统中发挥着重要作用。由于缺乏抗病毒药物，且疫苗存在显著的不良反应和较低的可及性，针对E蛋白的药物开发正受到研究人员的高度关注。本综述探讨了动物病毒中E蛋白的结构和基因组多样性，特别关注黄病毒、冠状病毒和疱疹病毒。E蛋白的病毒孔蛋白活性会损害宿主细胞膜并引发炎症，从而加速疾病进展。该综述还解释了病毒孔蛋白介导的含NOD样受体家族吡咯结构域3（NLRP3）、Toll样受体（TLR）、核苷酸结合寡聚化结构域（NOD）样受体（NLR）以及视黄酸诱导基因I（RIG-I）样受体（RLR）相关的细胞机制在病毒介导的炎症中的作用。由于E蛋白的功能域保守，它被认为是一个有前景的抗病毒靶点。本综述还根据计算、体外和体内研究，列举了在抗病毒药物开发中E蛋白的天然和合成抑制剂。E蛋白与细胞膜结合的普遍保守能力以及有限的结构数据给选择性药物抑制带来了重大挑战。本综述强调，E蛋白与多种病毒因子共同作用将提高治疗效果，同时降低病毒耐药性。此外，针对E蛋白的广谱抑制剂有可能产生单一治疗方案来对抗包括多种病毒株在内的病毒感染。总之，针对E蛋白的药物在开发具有高药物特异性和低病毒耐药性的潜在抗病毒药物方面将具有益处。
