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All Studies   Meta Analysis    Recent:   

Antiviral activity of curcumin and its analogs selected by an artificial intelligence-supported activity prediction system in SARS-CoV-2-infected VeroE6 cells

Teshima et al., Natural Product Research, doi:10.1080/14786419.2023.2194647
Mar 2023  
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Curcumin for COVID-19
14th treatment shown to reduce risk in February 2021
 
*, now known with p = 0.000000046 from 26 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
In Vitro study of curcumin and its analogs with 6 of 8 compounds showing SARS-CoV-2 antiviral activity with EC50 values <30μM and binding inhibitory activity with IC20 values <30μM.
In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spike Note A, Nag, Moschovou, Kandeil, Singh (B), Boseila (and specifically the receptor binding domain Note B, Kant, Srivastava, Eleraky), Mpro Note C, Moschovou, Kandeil, Srivastava, Naderi Beni, Rajagopal, Rampogu, Sekiou, Singh, Winih Kinasih, Thapa, Bahun, Eleraky, Boseila, RNA-dependent RNA polymerase Note D, Singh (C), Eleraky, ACE2 Note E, Singh (B), Thapa, Alkafaas, nucleocapsid Note F, Hidayah, Suravajhala, and nsp10 Note G, Suravajhala proteins. In Vitro studies demonstrate inhibition of the spike Note A, Mohd Abd Razak (and specifically the receptor binding domain Note B, Goc (B)), Mpro Note C, Bahun, Guijarro-Real, Mohd Abd Razak, Wu, ACE2 Note E, Goc (B), and TMPRSS2 Note H, Goc (B) proteins. In Vitro studies demonstrate efficacy in Calu-3 Note I, Bormann, A549 Note J, Mohd Abd Razak, 293T Note K, Zhang, HEK293-hACE2 Note L, Nittayananta, Wu, 293T/hACE2/TMPRSS2 Note M, Septisetyani, Vero E6 Note N, Bormann, Eleraky, Kandeil, Leka, Mohd Abd Razak, Nittayananta, Singh, Teshima, Marín-Palma, and SH-SY5Y Note O, Nicoliche cells. Curcumin is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants Kant, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells Marín-Palma, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress Zhang.
Teshima et al., 28 Mar 2023, peer-reviewed, 10 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Supplemental online material Antiviral activity of curcumin and its analogs selected by an artificial intelligencesupported activity prediction system in SARS-CoV-2-infected VeroE6 cells
Koji Teshima, Takeshi Tanaka, Zhengmao Ye, Ken Ikeda, Takao Matsuzaki, Tamotsu Shiroma, Ayumu Muroya, Masato Hosoda, Mayo Yasugi, Hirotsugu Komatsu
Curcumin has been reported to exert its anti-SARS-CoV-2 activity by inhibiting the binding of spike receptor-binding domain (RBD) to angiotensin-converting enzyme-2 (ACE2). To identify more potent compounds, we evaluated the antiviral activities of curcumin and its analogs in SARS-CoV-2-infected cells. An artificial intelligence-supported activity prediction system was used to select the compounds, and 116 of the 334 curcumin analogs were proposed to have spike RBD-ACE2 binding inhibitory activity. These compounds were narrowed down to eight compounds for confirmatory studies. Six out of the eight compounds showed antiviral activity with EC50 values of less than 30 µM and binding inhibitory activity with IC20 values of less than 30 µM. Structure-activity relationship analyses revealed that the double bonds in the carbon chain connecting the two phenolic groups were essential for both activities. X-ray co-crystallography studies are needed to clarify the true binding pose and design more potent derivatives.
Cells African green monkey kidney cell line VeroE6 and VeroE6 expressing the transmembrane serine protease TMPRSS2 (VeroE6/TMPRSS2, Matsuyama et al. 2020) were purchased from the National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan. VeroE6 cells were cultured in minimal essential medium (MEM; Sigma-Aldrich, MO, USA) supplemented with 10% fetal bovine serum (FBS) and antibiotics. VeroE6/TMPRSS2 cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Thermo Fisher Scientific, MA, USA) supplemented with 5% FBS and 1 mg/mL G418 (Nacalai, Kyoto, Japan). The cells were grown at 37°C in a CO2 incubator. Virus SARS-CoV-2 viral strain JPN/TY/WK/521 was provided by the National Institute of Infectious Diseases, Tokyo, Japan. Viruses were propagated in monolayers of VeroE6/TMPRSS2 cells in DMEM supplemented with 2% FBS and 1 mg/mL G418 at a multiplicity of infection of 0.01. Virus titration Infectivity was titrated by a focus-forming assay as described previously (Yasugi et al. 2013 ) with slight modifications. Viruses were serially diluted 10-fold in DMEM supplemented with 2% FBS and infected with confluent VeroE6 cells for 8 h. The cells were fixed with 4% paraformaldehyde for 15 min and washed with phosphate-buffered saline (PBS) three times. After the cells were permeabilized with 0.1% Triton ® X-100 for 15 min and washed with PBS three times, they were incubated with rabbit anti-nucleocapsid monoclonal antibody (Thermo Fisher Scientific) at a..
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