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All Studies   Meta Analysis    Recent:   

Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions

Goc et al., PLOS ONE, doi:10.1371/journal.pone.0253489
Jun 2021  
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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 56 polyphenols showing that curcumin has high binding affinity to the RBD of the SARS-CoV-2 spike protein, inhibits ACE2 at non-toxic concentrations, and decreases activity of TMPRSS2. Promising results were also seen for brazilin and theaflavin-3,3’-digallate.
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.
Goc et al., 17 Jun 2021, peer-reviewed, 4 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions
Anna Goc, Waldemar Sumera, Matthias Rath, Aleksandra Niedzwiecki
PLOS ONE, doi:10.1371/journal.pone.0253489
In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3'-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3'-digallate at 25 μg/ml and curcumin above 10 μg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3'-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3'-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.
Supporting information S1 File. Raw Western blot images. (PPTX) Author Contributions Conceptualization: Anna Goc. Data curation: Matthias Rath, Aleksandra Niedzwiecki. Formal analysis: Anna Goc, Waldemar Sumera. Visualization: Anna Goc, Waldemar Sumera, Aleksandra Niedzwiecki. Writing -original draft: Anna Goc, Waldemar Sumera, Matthias Rath, Aleksandra Niedzwiecki. Writing -review & editing: Anna Goc, Waldemar Sumera, Aleksandra Niedzwiecki.
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Here, we provide ' 'experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, ' 'theaflavin-3,3’-digallate, and curcumin displayed the highest binding with the ' 'receptor-binding domain of spike protein, inhibiting viral attachment to the human ' 'angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 ' 'virions. Both, theaflavin-3,3’-digallate at 25 μg/ml and curcumin above 10 μg/ml ' 'concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at ' 'the same time its activity in both cell-free and cell-based assays. Our study also ' 'demonstrates that brazilin and theaflavin-3,3’-digallate, and to a still greater extent, ' 'curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and ' 'cell-based assays. Similar pattern was observed with cathepsin L, although only ' 'theaflavin-3,3’-digallate showed a modest diminution of cathepsin L expression at protein ' 'level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. 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