tetano
Editor, Senior Moderator
FASEB J
. 2021 Apr;35(4):e21360.
doi: 10.1096/fj.202001792R.
A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study
Zhen-Zhen Wang[SUP] 1 2 [/SUP], Kun Li[SUP] 3 [/SUP], Anish R Maskey[SUP] 2 [/SUP], Weihua Huang[SUP] 4 [/SUP], Anton A Toutov[SUP] 5 [/SUP], Nan Yang[SUP] 2 6 [/SUP], Kamal Srivastava[SUP] 2 6 [/SUP], Jan Geliebter[SUP] 2 7 [/SUP], Raj Tiwari[SUP] 2 7 [/SUP], Mingsan Miao[SUP] 1 [/SUP], Xiu-Min Li[SUP] 2 7 [/SUP]
Affiliations
Abstract
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-? 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-1?, 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.
Keywords: COVID-19 and SARS; anti-viral; apoptosis; berberine; computational modeling.
. 2021 Apr;35(4):e21360.
doi: 10.1096/fj.202001792R.
A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study
Zhen-Zhen Wang[SUP] 1 2 [/SUP], Kun Li[SUP] 3 [/SUP], Anish R Maskey[SUP] 2 [/SUP], Weihua Huang[SUP] 4 [/SUP], Anton A Toutov[SUP] 5 [/SUP], Nan Yang[SUP] 2 6 [/SUP], Kamal Srivastava[SUP] 2 6 [/SUP], Jan Geliebter[SUP] 2 7 [/SUP], Raj Tiwari[SUP] 2 7 [/SUP], Mingsan Miao[SUP] 1 [/SUP], Xiu-Min Li[SUP] 2 7 [/SUP]
Affiliations
- PMID: 33749932
- DOI: 10.1096/fj.202001792R
Abstract
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-? 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-1?, 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.
Keywords: COVID-19 and SARS; anti-viral; apoptosis; berberine; computational modeling.