Abstract
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.
【초록키워드】 immune response, Gene Expression, Trial, Pneumonia, SARS-COV-2 infection, lung, metabolism, Spread, Hemolysis, mice, death, pathway, in vivo, cell death, COVID-19 patients, COVID-19 epidemic, mouse-adapted SARS-CoV-2, dysregulation, Support, Phenotypes, NAD+, treat, inflammatory cell infiltration, PROTECT, develop, caused, significantly, investigated, suppressed, rescued, effect of treatment, effective strategy, treating COVID-19 patient, 【제목키워드】 Pneumonia, mouse model, NAD+,