论文标题

人-NCOV蛋白 - 蛋白质相互作用网络的计算建模

Computational modeling of Human-nCoV protein-protein interaction network

论文作者

Saha, Sovan, Halder, Anup Kumar, Bandyopadhyay, Soumyendu Sekhar, Chatterjee, Piyali, Nasipuri, Mita, Basu, Subhadip

论文摘要

Covid-19在2020年创造了一个全球大流行,具有高发病率和死亡率。新型冠状病毒(NCOV),也称为严重的急性呼吸综合征冠状病毒2(SARS-COV2),是这种致命疾病的原因。国际病毒分类法委员会(ICTV)宣布,NCOV在2003年与SARS-COV流行相似(89%的相似性)。文献中有数量有限的临床验证的人-NCOV蛋白相互作用数据。有了这一假设,目前的工作着重于使用经过实验验证的SARS-COV人类蛋白质相互作用来开发NCOV人类蛋白质相互作用网络的计算模型。最初,使用易感感染感染的(SIS)模型,在SARS-COV人类相互作用网络中鉴定了Level-1和2级人类散布蛋白。这些蛋白被认为是NCOV诱饵蛋白的潜在人类靶标。基于基因的模糊亲和力函数已用于以99.98%的特异性阈值构建NCOV-HUMAN蛋白相互作用网络。这也确定了人类蛋白质交互网络中Covid-19的1级人类散布器。随后使用SIS模型确定了2级人类散布器。最终,使用7种潜在的FDA列出的Covid-19列出的药物对衍生的宿主 - 病原体相互作用网络进行了验证,该药物在已知的药物靶蛋白和已识别的散布蛋白之间具有显着重叠。

COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins.

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