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Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2

Kandeil et al., Pathogens, doi:10.3390/pathogens10060758
Jun 2021  
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Vero E6 In Vitro study showing curcumin, hesperidin, and quercetin significantly inhibited SARS-CoV-2 replication, and In Silico analysis with promising Mpro and spike docking results.
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, and Vero E6 Note N, Bormann, Eleraky, Kandeil, Leka, Mohd Abd Razak, Nittayananta, Singh, Teshima, Marín-Palma 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.
Study covers curcumin and quercetin.
Kandeil et al., 15 Jun 2021, peer-reviewed, 11 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2
Ahmed Kandeil, Ahmed Mostafa, Omnia Kutkat, Yassmin Moatasim, Ahmed A Al-Karmalawy, Adel A Rashad, Ahmed E Kayed, Azza E Kayed, Rabeh El-Shesheny, Ghazi Kayali, Mohamed A Ali
Pathogens, doi:10.3390/pathogens10060758
Until now, there has been no direct evidence of the effectiveness of repurposed FDAapproved drugs against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections. Although curcumin, hesperidin, and quercetin have broad spectra of pharmacological properties, their antiviral activities against SARS-CoV-2 remain unclear. Our study aimed to assess the in vitro antiviral activities of curcumin, hesperidin, and quercetin against SARS-CoV-2 compared to hydroxychloroquine and determine their mode of action. In Vero E6 cells, these compounds significantly inhibited virus replication, mainly as virucidal agents primarily indicating their potential activity at the early stage of viral infection. To investigate the mechanism of action of the tested compounds, molecular docking studies were carried out against both SARS-CoV-2 spike (S) and main protease (Mpro) receptors. Collectively, the obtained in silico and in vitro findings suggest that the compounds could be promising SARS-CoV-2 Mpro inhibitors. We recommend further preclinical and clinical studies on the studied compounds to find a potential therapeutic targeting COVID-19 in the near future.
Data Availability Statement: The data presented in this study are available within the article and Supplementary Materials. Conflicts of Interest: The authors declare no conflict of interest.
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