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10.1096/fj.202001792R

http://scihub22266oqcxt.onion/10.1096/fj.202001792R
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suck abstract from ncbi


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pmid33749932      FASEB+J 2021 ; 35 (4): e21360
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  • A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study #MMPMID33749932
  • Wang ZZ; Li K; Maskey AR; Huang W; Toutov AA; Yang N; Srivastava K; Geliebter J; Tiwari R; Miao M; Li XM
  • FASEB J 2021[Apr]; 35 (4): e21360 PMID33749932show ga
  • The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-gamma production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1alpha, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.
  • |*COVID-19 Drug Treatment[MESH]
  • |*COVID-19/metabolism[MESH]
  • |*Models, Biological[MESH]
  • |*Severe Acute Respiratory Syndrome/drug therapy/metabolism[MESH]
  • |Administration, Oral[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |Berberine/*pharmacology[MESH]
  • |Cell Line[MESH]
  • |Computer Simulation[MESH]
  • |Gene Expression Regulation/*drug effects[MESH]
  • |Humans[MESH]
  • |Pandemics[MESH]
  • |SARS-CoV-2/*metabolism[MESH]


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