Gene variants of coagulation related proteins that interact with SARS-CoV-2.
Gene variants of coagulation related proteins that interact with SARS-CoV-2.
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与 SARS-CoV-2 相互作用的凝血相关蛋白的基因变体。
DOI：
10.1371/journal.pcbi.1008805
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发表时间：
2021-03
影响因子：
4.3
通讯作者：
Kimchi-Sarfaty C
中科院分区：
文献类型：
--
作者：
Holcomb D;Alexaki A;Hernandez N;Hunt R;Laurie K;Kames J;Hamasaki-Katagiri N;Komar AA;DiCuccio M;Kimchi-Sarfaty C
血栓形成是公认的2019年冠状病毒病(新冠肺炎)的并发症，通常与不良预后有关。凝血和炎症之间存在着公认的联系，然而，与新冠肺炎相关的血栓形成事件的程度值得进一步研究。多聚(A)结合蛋白胞质4(PABPC4)、丝氨酸/半胱氨酸蛋白酶抑制因子分支G成员1(SERPING1)和维生素K环氧化物还原酶复合体1(VKORC1)都是与凝血有关的蛋白，它们都与SARS蛋白相互作用。我们通过计算研究了它们与SARS-CoV-2蛋白的相互作用，并以VKORC1为例，详细描述了它与ORF7a的结合。我们检查了这些蛋白中每一种的变异在人群中的出现情况，并询问了它们对新冠肺炎严重程度的潜在贡献。潜在的机制，其中一些变种可能有助于疾病，提出。其中一些变异在受到严重新冠肺炎影响的少数群体中流行。因此，我们建议围绕这些变异的进一步研究可能有助于更好地了解少数群体的疾病发病机制，并提供更有见地的治疗方法。新冠肺炎的常见并发症之一是凝血增加，尤其是肺部。传染病会引起炎症，而炎症又会导致血液凝结增加。然而，新冠肺炎患者肺部凝块形成的程度表明，这可能与更直接的联系有关。我们鉴定了三种人类蛋白质，它们间接参与了血液凝固级联反应，并已被证明与SARS病毒的蛋白质相互作用，SARS病毒与新型冠状病毒关系密切。我们通过计算研究了这些人类蛋白与病毒蛋白之间的相互作用。我们寻找这些蛋白质的遗传变异，并研究它们是如何在种群中分布的。我们调查了这些基因的变异是否会影响新冠肺炎的严重程度。围绕这些变异的进一步研究可能会为新冠肺炎的发病机制提供线索，特别是在少数群体中。
Thrombosis is a recognized complication of Coronavirus disease of 2019 (COVID-19) and is often associated with poor prognosis. There is a well-recognized link between coagulation and inflammation, however, the extent of thrombotic events associated with COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) and Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), which are all proteins linked to coagulation, have been shown to interact with SARS proteins. We computationally examined the interaction of these with SARS-CoV-2 proteins and, in the case of VKORC1, we describe its binding to ORF7a in detail. We examined the occurrence of variants of each of these proteins across populations and interrogated their potential contribution to COVID-19 severity. Potential mechanisms, by which some of these variants may contribute to disease, are proposed. Some of these variants are prevalent in minority groups that are disproportionally affected by severe COVID-19. Therefore, we are proposing that further investigation around these variants may lead to better understanding of disease pathogenesis in minority groups and more informed therapeutic approaches. Increased blood clotting, especially in the lungs, is a common complication of COVID-19. Infectious diseases cause inflammation, which in turn can contribute to increased blood clotting. However, the extent of clot formation that is seen in the lungs of COVID-19 patients suggests that there may be a more direct link. We identified three human proteins that are involved indirectly in the blood clotting cascade and have been shown to interact with proteins of SARS virus, which is closely related to the novel coronavirus. We examined computationally the interaction of these human proteins with the viral proteins. We looked for genetic variants of these proteins and examined how they are distributed across populations. We investigated whether variants of these genes could impact severity of COVID-19. Further investigation around these variants may provide clues for the pathogenesis of COVID-19, particularly in minority groups.
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影响因子：
14.9
作者：
Cartegni, L;Wang, JH;Krainer, AR
通讯作者：
Krainer, AR
影响因子：
3.7
作者：
Chaudhury S;Berrondo M;Weitzner BD;Muthu P;Bergman H;Gray JJ
通讯作者：
Gray JJ
DOI：
10.1016/s0140-6736(08)61348-3
发表时间：
2008-11-22
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ennis S;Jomary C;Mullins R;Cree A;Chen X;Macleod A;Jones S;Collins A;Stone E;Lotery A
通讯作者：
Lotery A
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
DOI：
10.1038/ejhg.2016.17
发表时间：
2016-08
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Cook JP;Morris AP
通讯作者：
Morris AP