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A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity

Nittayananta et al., Virology Journal, doi:10.1186/s12985-023-02282-x
Jan 2024  
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Curcumin for COVID-19
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In Vitro study showing that a novel oro-nasal curcumin film spray inhibits SARS-CoV-2 and influenza virus infection of cells while enhancing mucosal innate immunity. The spray demonstrated potent dose-dependent antiviral activity against SARS-CoV-2, influenza A H1N1, and influenza B viruses via plaque reduction assay. It was nontoxic to epithelial cell lines at antiviral concentrations. Additionally, the spray significantly induced secretion of antimicrobial peptides LL-37, HD-5 and anti-inflammatory cytokine IL-6 by oral keratinocytes, which may prevent viral entry and lung injury. Authors conclude that the spray could effectively inhibit SARS-CoV-2 and influenza infection while modulating inflammation.
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) (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, 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.
Nittayananta et al., 23 Jan 2024, peer-reviewed, 8 authors. Contact:
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity
Wipawee Nittayananta, Hatairat Lerdsamran, Nopporn Chutiwitoonchai, Aornrutai Promsong, Teerapol Srichana, Kesinee Netsomboon, Jarunee Prasertsopon, Jaruta Kerdto
Virology Journal, doi:10.1186/s12985-023-02282-x
Background Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza virus is still a major worldwide health concern. Plants are a good source of bioactive compounds to be used as preventive measures for both inhibiting the virus binding and enhancing mucosal innate immunity. Curcumin has been shown to possess antiviral activity and modulate innate immunity. Therefore, the purpose of this study was to develop an oro-nasal film spray containing curcumin and determine its antiviral activity against SARS-CoV-2 and influenza virus infection, as well as its effects on mucosal innate immunity and inflammatory cytokines in vitro. Methods The antiviral activity of the film spray against SARS-CoV-2, influenza A/H1N1, A/H3N2, and influenza B was assessed in vitro by plaque reduction assay. Cytotoxicity of the film spray to oral keratinocytes and nasal epithelial cells was assessed by MTT assay, and cytotoxicity to Vero and MDCK cells was assessed by an MTS-based cytotoxicity assay. Oral and nasal innate immune markers in response to the film spray were determined by ELISA and by a commercial Milliplex Map Kit, respectively. Results Our data show that the film spray containing curcumin can inhibit both SARS-CoV-2 and influenza virus infections while maintaining cell viability. Results obtained among 4 viruses revealed that curcumin film spray demonstrated the highest inhibitory activity against SARS-CoV-2 with the lowest EC 50 of 3.15 µg/ml and the highest SI value of 4.62, followed by influenza B (EC 50 = 6.32 µg/ml, SI = 2.04), influenza A/H1N1 (EC 50 = 7.24 µg/ml, SI = 1.78), and influenza A/H3N2 (EC 50 > 12.5 µg/ml, SI < 1.03), respectively. Antimicrobial peptides LL-37 and HD-5, IL-6 and TNF-α produced by oral keratinocytes were significantly induced by the film spray, while hBD2 was significantly reduced. Conclusion Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.
Author contributions W.N. designed the study and wrote the proposal, W.N., N.C., K.N., and J.K. applied for the research funding; W.N., H.L., N.C., A.P., T.S. interpreted data and drafted manuscript. H.L., N.C., A.P., T.S., K.N., J.P. performed the experiments. W.N., H.L., N.C., A.P., T.S., and K.N. participated in reviewing and editing the final manuscript. All authors have read and agreed to the published version of the manuscript. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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