冠状病毒感染相关多器官功能障碍综合征分子机制和干预药物的生物信息学预测及其对新型冠状病毒肺炎的意义

Bioinformatics analysis on molecular mechanism and intervention drugs of coronavirus infection-related multiple organ dysfunction syndrome and their significances for coronavirus disease 2019

摘要:

目的 通过对冠状病毒感染相关多器官功能障碍综合征(MODS)分子机制及干预药物的生物信息学预测,探索其对新型冠状病毒肺炎(COVID-19)的意义。方法 从公共开放的基因表达数据库(GEO)获取冠状病毒全基因组表达谱数据,利用R语言Impute程序包进行数据标准化,Limma程序包筛选差异表达基因,Robust rank aggregation算法筛选差异显著性基因。进一步的表观调控机制分析利用R语言Clusterprofile程序包,进行GO功能富集、KEGG通路富集分析。再利用本课题组前期建立的表观精准治疗预测平台(EpiMed),筛选潜在干预药物。结果 在SARS冠状病毒(SARS-CoV)感染的小鼠中,肺损伤相关通路为哮喘信号通路,心脏损伤相关通路为病毒性心肌炎信号通路,肾脏损伤相关通路为近端小管碳酸氢盐回收信号通路,肝脏损伤相关通路为非酒精性脂肪肝病信号通路,造血功能损伤相关通路为造血细胞谱系信号通路。EpiMed平台筛选出对SARS-CoV感染诱发的 MODS具有潜在干预作用的药物,包括肿瘤坏死因子(TNF-α)抑制剂、虎杖、利托那韦、鱼腥草、奈韦拉平、败酱、泛昔洛韦、西多福韦、连翘、α干扰素、磷酸氯喹、瑞德西韦和阿比朵尔。结论 SARS-CoV感染可通过器官特异性相关通路引起MODS,并基于这些通路预测出一系列潜在干预药物,有待进一步通过体内外实验和临床验证。这有助于指导COVID-19相关MODS的临床和基础研究。

Abstract:

Objective To explore the significance of coronavirus infection-related multiple organ dysfunction syndrome (MODS) following coronavirus disease 2019 (COVID-19) by bioinformatics prediction for molecular mechanism and intervention drugs. MethodsAfter the whole genome expression profile of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was obtained from the public database Gene Expression Omnibus (GEO), the Impute package of R language, Limma package and the Robust Rank Aggregation (RRA) algorithm were used respectively to standardize the data, screen differential expression genes (DEGs), and screen significant DEGs. Then epigenomic mechanism analysis was performed using the R language Clusterprofile package for GO function enrichment and KEGG pathway enrichment analysis. EpiMed (Epigenomic Precision Medicine Prediction platform) established earlier by us was used to screen potential intervention drugs. Results Bioinformatics analysis indicated that in the SARS-CoV-2 infected mice, lung injury was based on asthma signaling pathways, heart damage on viral myocarditis signaling pathways, kidney damage on proximal tubule bicarbonate recycle signaling pathways, liver injury on nonalcoholic fatty liver disease signaling pathways, and hematopoietic function damage on hematopoietic cell lineage signaling pathways. EpiMed platform screened out the drugs with potential intervention effect on SARS-CoV-2 infection-induced MODS, including TNF-1 inhibitors, polygonum cuspidatum, ritonavir, houttuynia cordata, nevirapine, patrinia, famciclovir, siduofovir, forsythia, interferon-α, chloroquine phosphate, remdesivir and abidol. Conclusion SARS-CoV-2 infection can cause MODS through organ-specific related pathways, and a series of potential intervention drugs are predicted based on these pathways, which need further in vivo and in vitro experiments and clinical validation. Our study helps to guide clinical and basic research on COVID-19 related MODS.