Abstract:
Responsible for COVID-19, SARS-CoV-2 is a coronavirus in which contagious variants continue to appear. Therefore, some population groups have demonstrated greater susceptibility to contagion and disease progression. For these reasons, several researchers have been studying the SARS-CoV-2/human interactome to understand the pathophysiology of COVID-19 and develop new pharmacological strategies. D. melanogaster is a versatile animal model with approximately 90 % human protein orthology related to SARS-CoV-2/human interactome and is widely used in metabolic studies. In this context, our work assessed the potential interaction between human proteins (ZNF10, NUP88, BCL2L1, UBC9, and RBX1) and their orthologous proteins in D. melanogaster (gl, Nup88, Buffy, ubc9, and Rbx1a) with proteins from SARS-CoV-2 (nsp3, nsp9, E, ORF7a, N, and ORF10) using computational approaches. Our results demonstrated that all the proteins have the potential to interact, and we compared the binding sites between humans and fruit flies. The stability and consistency in the structure of the gl_nsp3 complex, specifically, could be crucial for its specific biological functions. Lastly, to enhance the understanding of the influence of host factors on coronavirus infection, we also analyse the mRNA expression of the five genes (mbo, gl, lwr, Buffy, and Roc1a) responsible for encoding the fruit fly proteins. Briefly, we demonstrated that those genes were differentially regulated according to diets, sex, and age. Two groups showed higher positive gene regulation than others: females in the HSD group and males in the aging group, which could imply a higher virus-host susceptibility. Overall, while preliminary, our work contributes to the understanding of host defense mechanisms and potentially identifies candidate proteins and genes for in vivo viral studies against SARS-CoV-2.
摘要:
负责COVID-19,SARS-CoV-2是一种不断出现传染性变体的冠状病毒。因此,一些人群表现出更容易感染和疾病进展。由于这些原因,一些研究人员一直在研究SARS-CoV-2/人类相互作用组,以了解COVID-19的病理生理学并开发新的药理学策略。D.melanogaster是一种多功能的动物模型,具有约90%的人蛋白质与SARS-CoV-2/人相互作用组相关,并广泛用于代谢研究。在这种情况下,我们的工作评估了人类蛋白质(ZNF10,NUP88,BCL2L1,UBC9和RBX1)与其直系同源蛋白之间的潜在相互作用。黑腹(gl,努普88巴菲,ubc9和Rbx1a)与SARS-CoV-2(nsp3,nsp9,E,ORF7a,N,和ORF10)使用计算方法。我们的结果表明,所有的蛋白质都有相互作用的潜力,我们比较了人类和果蝇之间的结合位点。gl_nsp3配合物结构的稳定性和一致性,具体来说,可能对其特定的生物学功能至关重要。最后,为了增强对宿主因素对冠状病毒感染的影响的理解,我们还分析了这五个基因的mRNA表达(mbo,gl,lwr,巴菲,和Roc1a)负责编码果蝇蛋白。简而言之,我们证明了这些基因根据饮食而受到差异调节,性别,和年龄。两组均表现出较高的正基因调控:HSD组的女性和衰老组的男性,这可能意味着更高的病毒宿主易感性。总的来说,虽然初步,我们的工作有助于理解宿主防御机制,并可能确定候选蛋白和基因,用于体内抗SARS-CoV-2的病毒研究。