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Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms

Marín-Palma et al., Molecules, doi:10.3390/molecules26226900
Nov 2021  
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Curcumin for COVID-19
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In Vitro study showing antiviral and anti-inflammatory effects of curcumin during SARS-CoV-2 infection. Inhibition was seen with Vero E6 cells pre-infection and post-infection, and with D614G and the delta variant. The anti-inflammatory effect was shown with peripheral blood mononuclear cells.
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.
Marín-Palma et al., 16 Nov 2021, peer-reviewed, 9 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms
Damariz Marín-Palma, Jorge H Tabares-Guevara, María I Zapata-Cardona, Lizdany Flórez-Álvarez, Lina M Yepes, Maria T Rugeles, Wildeman Zapata-Builes, Juan C Hernandez, Natalia A Taborda
Molecules, doi:10.3390/molecules26226900
Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre-post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre-post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.
Institutional Review Board Statement: This study was approved by the ethics committee of the Universidad Cooperativa de Colombia (Acta BIO106). It was carried out keeping good records, practicing good data collection and management, transparency of data-sharing, and realistic representation of study results. The data were analyzed anonymously. All donors were adults, read, and signed an informed consent. All research protocols were made according to the principles of the Declaration of Helsinki. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Data Availability Statement: All data generated or analyzed during this study are included in this published article (and its supporting information files). Conflicts of Interest: The authors declare no conflict of interest. Sample Availability: Samples of the compounds are available from the authors.
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