《BioRxiv,5月17日,Nrf2 Activator PB125 as a Potential Therapeutic Agent Against COVID-19》

  • 来源专题:COVID-19科研动态监测
  • 编译者: zhangmin
  • 发布时间:2020-05-18
  • Nrf2 Activator PB125 as a Potential Therapeutic Agent Against COVID-19

    Joe M McCord, Brooks M. Hybertson, Adela Cota-Gomez, Bifeng Gao

    doi: https://doi.org/10.1101/2020.05.16.099788

    Abstract

    Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2 activating composition PB125 down regulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-Cov-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells we report the marked down regulation by PB125 of 36 genes encoding cytokines. These include IL1-beta, IL6, TNF-alpha the cell adhesion molecules ICAM1, VCAM1, and E-selectin, and a group of IFN-gamma-induced genes.

    *注,本文为预印本论文手稿,是未经同行评审的初步报告,其观点仅供科研同行交流,并不是结论性内容,请使用者谨慎使用.

  • 原文来源:https://www.biorxiv.org/content/10.1101/2020.05.16.099788v1
相关报告
  • 《BioRxiv,3月12日,A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-03-13
    • A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19 Yiyue Ge, Tingzhong Tian, Sulin Huang, Fangping Wan, Jingxin Li, Shuya Li, Hui Yang, Lixiang Hong, Nian Wu, Enming Yuan, Lili Cheng, Yipin Lei, Hantao Shu, Xiaolong Feng, Ziyuan Jiang, Ying Chi, Xiling Guo, Lunbiao Cui, Liang Xiao, Zeng Li, Chunhao Yang, Zehong Miao, Haidong Tang, Ligong Chen, Hainian Zeng, Dan Zhao, Fengcai Zhu, Xiaokun Shen, Jianyang Zeng doi: https://doi.org/10.1101/2020.03.11.986836 Abstract The global spread of SARS-CoV-2 requires an urgent need to find effective therapeutics for the treatment of COVID-19. We developed a data-driven drug repositioning framework, which applies both machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. The retrospective study using the past SARS-CoV and MERS-CoV data demonstrated that our machine learning based method can successfully predict effective drug candidates against a specific coronavirus. *注,本文为预印本论文手稿,是未经同行评审的初步报告,其观点仅供科研同行交流,并不是结论性内容,请使用者谨慎使用.
  • 《Medical Hypotheses,5月30日,N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2》

    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2020-05-31
    • N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2 Author links open overlay panelFrancis L.PoeJoshuaCorn Show more https://doi.org/10.1016/j.mehy.2020.109862 Abstract COVID-19, a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity. T cell exhaustion, high viral load, and high levels of TNF-ɑ, IL1β, IL6, IL10 have been associated with severe SARS-CoV-2. Cytokine and antigen overstimulation are potentially responsible for poor humoral response to the virus. Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. In human clinical trials, NAC can be used to replenish glutathione stores and increase the proliferative response of T cells.