肠道菌群
生物
抗生素
内啡肽酶
微生物学
微生物群
免疫系统
免疫学
生物化学
生物信息学
基因
核糖核酸
核糖核酸酶P
作者
Yao Ma,Min Luo,Yusheng Deng,Xiaoman Yang,Xionglue Wang,Guozhong Chen,Zixin Qin,Yun Deng,Meiling Nan,Yang Chen,Pei‐Hui Wang,Hong Wei,Lijuan Han,Xiaodong Fang,Zhi Li
标识
DOI:10.3389/fcimb.2022.896504
摘要
The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids.
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