登革热病毒是由包括衣壳在内的三种结构蛋白组成的单正链RNA病毒,信封,和前体膜,而七个非结构蛋白(NS1,NS2A,NS2B,NS3A,NS3B,NS4和NS5)。登革热是由登革热病毒(DENV)引起的病毒感染。DENV感染无症状或仅产生轻度疾病。然而,DENV偶尔会导致更严重的病例甚至死亡。没有针对登革热病毒感染的特定治疗方法。与蛋白质或抗体相比,治疗肽有几个重要的优点:它们体积小,易于合成,并有穿透细胞膜的能力。他们也有很高的活性,特异性,亲和力,毒性较小。基于已知的肽抑制剂,本研究使用丙氨酸和残基扫描技术设计了登革热病毒包膜蛋白的肽抑制剂。通过用Q21代替I21,用H14代替L14,用K28代替V28,增加了肽抑制剂的结合亲和力。新设计的具有单残基突变的肽抑制剂提高了肽抑制剂的结合亲和力。通过利用MD模拟和自由结合能计算进一步证实了新的有前途的肽抑制剂的抑制能力。分子动力学模拟表明,与野生型肽抑制剂相比,新设计的肽抑制剂表现出更高的稳定性。根据这些开发的肽的结合自由能MM(GB)SA,第一种肽抑制剂对登革热病毒包膜蛋白最有效。所有肽衍生物对包膜蛋白具有更高的结合亲和力,并且具有治疗登革病毒相关感染的潜力。在这项研究中,基于已经报道的肽抑制剂,为登革热病毒包膜蛋白开发了新的肽抑制剂。
Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven non-structural proteins (NS1, NS2A, NS2B, NS3A, NS3B, NS4, and NS5). Dengue is a viral infection caused by the dengue virus (DENV). DENV infections are asymptomatic or produce only mild illness. However, DENV can occasionally cause more severe cases and even death. There is no specific treatment for dengue virus infections. Therapeutic peptides have several important advantages over proteins or antibodies: they are small in size, easy to synthesize, and have the ability to penetrate the cell membranes. They also have high activity, specificity, affinity, and less toxicity. Based on the known peptide inhibitor, the current study designs peptide inhibitors for dengue virus envelope protein using an alanine and residue scanning technique. By replacing I21 with Q21, L14 with H14, and V28 with K28, the binding affinity of the peptide inhibitors was increased. The newly designed peptide inhibitors with single residue mutation improved the binding affinity of the peptide inhibitors. The inhibitory capability of the new promising peptide inhibitors was further confirmed by the utilization of MD simulation and free binding energy calculations. The molecular dynamics simulation demonstrated that the newly engineered peptide inhibitors exhibited greater stability compared to the wild-type peptide inhibitors. According to the binding free energies MM(GB)SA of these developed peptides, the first peptide inhibitor was the most effective against the dengue virus envelope protein. All peptide derivatives had higher binding affinities for the envelope protein and have the potential to treat dengue virus-associated infections. In this study, new peptide inhibitors were developed for the dengue virus envelope protein based on the already reported peptide inhibitor.