Treatment of SARS-CoV-2-induced pneumonia with NAD(+) and NMN in two mouse models.
Treatment of SARS-CoV-2-induced pneumonia with NAD(+) and NMN in two mouse models.
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在两种小鼠模型中使用 NAD 和 NMN 治疗 SARS-CoV-2 诱导的肺炎
DOI：
10.1038/s41421-022-00409-y
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发表时间：
2022-04-29
期刊：
影响因子：
33.5
通讯作者：
Xu, Zhiheng
中科院分区：
文献类型：
--
作者：
Jiang, Yisheng;Deng, Yongqiang;Pang, Huanhuan;Ma, Tiantian;Ye, Qing;Chen, Qi;Chen, Haiyang;Hu, Zeping;Qin, Cheng-Feng;Xu, Zhiheng
全球COVID-19疫情已在全球迅速蔓延，并导致超过500万人死亡。迫切需要制定有效的策略来治疗COVID-19患者。在这里，我们揭示了SARS-CoV-2感染导致小鼠中与NAD+代谢，免疫反应和细胞死亡相关的基因失调，与COVID-19患者相似。因此，我们研究了用NAD+及其中间体（NMN）治疗的效果，发现肺炎表型，包括SARS-CoV-2感染的肺中的过度炎性细胞浸润、溶血和栓塞被显著挽救。NAD+和NMN补充显著抑制细胞死亡。更引人注目的是，NMN补充剂可以保护30%感染致命的小鼠适应SARS-CoV-2的老年小鼠免于死亡。从机制上讲，我们发现NAD+或NMN补充部分挽救了SARS-CoV-2感染引起的基因表达和代谢紊乱。因此，我们的体内小鼠研究支持通过靶向NAD+途径治疗COVID-19患者的试验。
The global COVID-19 epidemic has spread rapidly around the world and caused the death of more than 5 million people. It is urgent to develop effective strategies to treat COVID-19 patients. Here, we revealed that SARS-CoV-2 infection resulted in the dysregulation of genes associated with NAD+ metabolism, immune response, and cell death in mice, similar to that in COVID-19 patients. We therefore investigated the effect of treatment with NAD+ and its intermediate (NMN) and found that the pneumonia phenotypes, including excessive inflammatory cell infiltration, hemolysis, and embolization in SARS-CoV-2-infected lungs were significantly rescued. Cell death was suppressed substantially by NAD+ and NMN supplementation. More strikingly, NMN supplementation can protect 30% of aged mice infected with the lethal mouse-adapted SARS-CoV-2 from death. Mechanically, we found that NAD+ or NMN supplementation partially rescued the disturbed gene expression and metabolism caused by SARS-CoV-2 infection. Thus, our in vivo mouse study supports trials for treating COVID-19 patients by targeting the NAD+ pathway.
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DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
影响因子：
4.4
作者：
Kojima, Toshiyuki;Obata, Kazushige;Karasuyama, Hajime
通讯作者：
Karasuyama, Hajime
影响因子：
46.9
作者：
Chua, Robert Lorenz;Lukassen, Soeren;Eils, Roland
通讯作者：
Eils, Roland
凋亡：心血管疾病的一种新调节机制。
影响因子：
4.5
作者：
Ji N;Qi Z;Wang Y;Yang X;Yan Z;Li M;Ge Q;Zhang J
通讯作者：
Zhang J
宿主病毒感染图谱揭示了重症 COVID-19 患者的特征
影响因子：
64.5
作者：
Bost, Pierre;Giladi, Amir;Amit, Ido
通讯作者：
Amit, Ido