Mesh : Humans RNA / metabolism Influenza A virus Influenza A Virus, H1N1 Subtype Influenza A Virus, H3N2 Subtype Coinfection Single-Chain Antibodies / pharmacology metabolism Coronavirus OC43, Human

来  源:   DOI:10.1038/s41598-024-52810-0   PDF(Pubmed)

Abstract:
With the lifting of COVID-19 non-pharmaceutical interventions, the resurgence of common viral respiratory infections was recorded in several countries worldwide. It facilitates viral co-infection, further burdens the already over-stretched healthcare systems. Racing to find co-infection-associated efficacy therapeutic agents need to be rapidly established. However, it has encountered numerous challenges that necessitate careful investigation. Here, we introduce a potential recombinant minibody-associated treatment, 3D8 single chain variable fragment (scFv), which has been developed as a broad-spectrum antiviral drug that acts via its nucleic acid catalytic and cell penetration abilities. In this research, we demonstrated that 3D8 scFv exerted antiviral activity simultaneously against both influenza A viruses (IAVs) and coronaviruses in three established co-infection models comprising two types of coronaviruses [beta coronavirus-human coronavirus OC43 (hCoV-OC43) and alpha coronavirus-porcine epidemic diarrhea virus (PEDV)] in Vero E6 cells, two IAVs [A/Puerto Rico/8/1934 H1N1 (H1N1/PR8) and A/X-31 (H3N2/X-31)] in MDCK cells, and a combination of coronavirus and IAV (hCoV-OC43 and adapted-H1N1) in Vero E6 cells by a statistically significant reduction in viral gene expression, proteins level, and approximately around 85%, 65%, and 80% of the progeny of \'hCoV-OC43-PEDV\', \'H1N1/PR8-H3N2/X-31\', and \'hCoV-OC43-adapted-H1N1\', respectively, were decimated in the presence of 3D8 scFv. Taken together, we propose that 3D8 scFv is a promising broad-spectrum drug for treatment against RNA viruses in co-infection.
摘要:
随着COVID-19非药物干预措施的解除,全球有几个国家记录了常见病毒性呼吸道感染的死灰复燃.它促进病毒共感染,进一步负担已经过度紧张的医疗保健系统。需要迅速建立寻找与共感染相关的功效治疗剂的竞赛。然而,它遇到了许多挑战,需要仔细调查。这里,我们介绍了一种潜在的重组微型抗体相关治疗方法,3D8单链可变片段(scFv),它已被开发为一种广谱抗病毒药物,通过其核酸催化和细胞渗透能力发挥作用。在这项研究中,我们证明了3D8scFv在三种已建立的共感染模型中同时对甲型流感病毒(IAV)和冠状病毒具有抗病毒活性,该模型包括两种类型的冠状病毒[β冠状病毒-人冠状病毒OC43(hCoV-OC43)和α冠状病毒-猪流行性腹泻病毒(PEDV)]在VeroE6细胞中,MDCK细胞中的两个IAV[A/波多黎各/8/1934H1N1(H1N1/PR8)和A/X-31(H3N2/X-31)],以及VeroE6细胞中冠状病毒和IAV(hCoV-OC43和适应的H1N1)的组合,通过病毒基因表达的统计学显着降低,蛋白质水平,大约85%左右,65%,和80%的“hCoV-OC43-PEDV”后代,\'H1N1/PR8-H3N2/X-31\',和\'hCoV-OC43-adapted-H1N1\',分别,在3D8scFv的存在下被抽取。一起来看,我们认为3D8scFv是一种有前途的广谱药物,用于治疗共感染的RNA病毒。
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