Esteves Eduardo, Mendes Vera M, Manadas Bruno, Lopes Rafaela, Bernardino Liliana, Correia Maria José, Barros Marlene, Esteves Ana Cristina, Rosa Nuno
Universidade Católica Portuguesa, Faculty of Dental Medicine (FMD), Center for Interdisciplinary Research in Health (CIIS), 3504-505 Viseu, Portugal.
Health Sciences Research Centre (CICS-UBI), Faculty of Health Sciences, University of Beira Interior, 6201-001 Covilhã, Portugal.
J Clin Med. 2022 Sep 22;11(19):5571. doi: 10.3390/jcm11195571.
COVID-19 is the most impacting global pandemic of all time, with over 600 million infected and 6.5 million deaths worldwide, in addition to an unprecedented economic impact. Despite the many advances in scientific knowledge about the disease, much remains to be clarified about the molecular alterations induced by SARS-CoV-2 infection. In this work, we present a hybrid proteomics and in silico interactomics strategy to establish a COVID-19 salivary protein profile. Data are available via ProteomeXchange with identifier PXD036571. The differential proteome was narrowed down by the Partial Least-Squares Discriminant Analysis and enrichment analysis was performed with FunRich. In parallel, OralInt was used to determine interspecies Protein-Protein Interactions between humans and SARS-CoV-2. Five dysregulated biological processes were identified in the COVID-19 proteome profile: Apoptosis, Energy Pathways, Immune Response, Protein Metabolism and Transport. We identified 10 proteins (KLK 11, IMPA2, ANXA7, PLP2, IGLV2-11, IGHV3-43D, IGKV2-24, TMEM165, VSIG10 and PHB2) that had never been associated with SARS-CoV-2 infection, representing new evidence of the impact of COVID-19. Interactomics analysis showed viral influence on the host immune response, mainly through interaction with the degranulation of neutrophils. The virus alters the host's energy metabolism and interferes with apoptosis mechanisms.
新冠病毒病是有史以来影响最大的全球大流行疾病,全球感染人数超过6亿,死亡人数达650万,此外还造成了前所未有的经济影响。尽管在关于该疾病的科学知识方面取得了许多进展,但关于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染所引起的分子改变仍有许多有待阐明。在这项研究中,我们提出了一种蛋白质组学与计算机模拟相互作用组学相结合的策略,以建立新冠病毒病唾液蛋白质谱。数据可通过蛋白质组交换库获取,标识符为PXD036571。通过偏最小二乘判别分析对差异蛋白质组进行筛选,并使用FunRich进行富集分析。同时,利用OralInt来确定人类与SARS-CoV-2之间的种间蛋白质-蛋白质相互作用。在新冠病毒病蛋白质组谱中鉴定出五个失调的生物学过程:细胞凋亡、能量途径、免疫反应、蛋白质代谢和转运。我们鉴定出10种从未与SARS-CoV-2感染相关联的蛋白质(激肽释放酶11、肌醇磷酸酶2、膜联蛋白A7、磷脂蛋白2、免疫球蛋白轻链可变区2-11、免疫球蛋白重链可变区3-43D、免疫球蛋白κ链可变区2-24、跨膜蛋白165、V-set和免疫球蛋白结构域包含蛋白10以及线粒体内膜转位酶2),这代表了新冠病毒病影响的新证据。相互作用组学分析显示病毒主要通过与中性粒细胞脱颗粒相互作用对宿主免疫反应产生影响。病毒改变宿主的能量代谢并干扰细胞凋亡机制。