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

Abstract

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.

Herbal medications and natural products for patients with covid-19 and diabetes mellitus: Potentials and challenges

“…A total of sixteen (16) most relevant research papers ( Abdollahi et al, 2019 ; Afsharpour et al, 2019 ; Braxas et al, 2019 ; Homayouni et al, 2018 , 2017 ; Khajebishak et al, 2019 ; Mashhadi et al, 2018 ; Ragheb et al, 2020 ; Santos-Lozano et al, 2019 ; Seyed Hashemi et al, 2021 ; Shokri-Mashhadi et al, 2021 ; Tabatabaie et al, 2020 ; Thota et al, 2020 ; Urakaze et al, 2021 ; Yao et al, 2019 ; Zhao et al, 2016 ) reporting clinical evidence of antidiabetic properties of the ten selected natural products met the criteria and were included in this review (57 less relevant ones were excluded). The second phase of the literature search resulted in 475 search items and only fifteen (15) most relevant additional research papers ( de Ligt et al, 2021 ; di Pierro et al, 2021 ; Elfiky, 2021 ; Hassaniazad et al, 2021 ; Kosari et al, 2021 ; Kumar et al, 2021 ; Marín-Palma et al, 2021 ; Pasquereau et al, 2021 ; Patel et al, 2021 ; Pendyala et al, 2021 ; Rahman et al, 2021 ; Refaat et al, 2021 ; Silveira et al, 2021 ; Tallei et al, 2020 ; Tito et al, 2021 ) reporting any available evidence of the anti-COVID-19 potential of these substances were also selected (460 articles comprising reviews and other less relevant papers were excluded). A cumulative sum of thirty-one (31) papers was retained and discussed in this review.…”

“…Similarly, in silico and i n vitro data has shown that curcumin has the potential to bind SARS-CoV-2 S-protein as well as ACE2 via covalent interactions ( Shanmugarajan et al, 2020 ; Patel et al, 2021 ), and clinical trials to check the effectiveness of various formulations of curcumin in COVID-19 patients are in progress. Interestingly, a recent study has shown that a pre-post-infection treatment with curcumin (10 µg/mL) in Vero E6 cells infected with the D614G strain and the Delta variant of SARS-CoV-2 has shown a strong antiviral effect against these viruses with an efficiency of 99.0% and 99.8% respectively ( Marín-Palma et al, 2021 ). According to the study, curcumin treatment also ameliorated the SARS-CoV-2 infection-mediated releases of the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) by the peripheral blood mononuclear cells ( Marín-Palma et al, 2021 ).…”

“…Interestingly, a recent study has shown that a pre-post-infection treatment with curcumin (10 µg/mL) in Vero E6 cells infected with the D614G strain and the Delta variant of SARS-CoV-2 has shown a strong antiviral effect against these viruses with an efficiency of 99.0% and 99.8% respectively ( Marín-Palma et al, 2021 ). According to the study, curcumin treatment also ameliorated the SARS-CoV-2 infection-mediated releases of the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) by the peripheral blood mononuclear cells ( Marín-Palma et al, 2021 ). Furthermore, a recent triple‐blind, RCT reported that supplementation with the nano-curcumin (Sinacurcumin®) soft gel 40 mg, four times daily (after breakfast, lunch, dinner, and before bedtime) for 2 weeks resulted in decreased serum levels of the proinflammatory cytokines (IFN-γ and IL-17) as well as downregulations of some genes associated with T-cells response ( TBX21 and FOXP3 ) in the treated subjects compared to placebo ( Hassaniazad et al, 2021 ).…”

“… c. Curcumin solution (10 µg/mL) d. Sinacurcumin® soft gel (4 mg four times daily for 2 weeks) Curcumin (Polyphenol) Curcumin (polyphenol) Curcumin (Polyphenol) Curcumin (Polyphenol) Curcumin ( https://pubchem.ncbi.nlm.nih.gov/compound/curcumin#section=2D-Structure ) RCT (healthy volunteers who are at a high risk of developing T2D) i n silico (SARS-CoV-2 and host proteins) In vitro (Vero E6 cells) RCT (COVID-19 patients) IAPP↓, GSK-3β↓, insulin resistance↓ ( Thota et al, 2020 ). Binds to host ACE2 and SARS-CoV-2 S-protein ( Patel et al, 2021 ; Shanmugarajan et al, 2020 ) IL-1β↓, IL-6↓, and IL-8↓, 99.0% D614G strain of SARS-CoV-2↓, 99.8% Delta variant of SARS-CoV-2↓ ( Marín-Palma et al, 2021 ). IFN-γ↓, IL-17↓, TBX21 gene expression↓, FOXP3 gene expression↓ ( Hassaniazad et al, 2021 ).…”

Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2

“…Patel et al described the role of curcumin and its derivatives as SARS-CoV-2 spike protein inhibitors [25]. Additionally, curcumin inhibits SARS-CoV-2 infection in vitro in Vero E6 cells [26]. Kumar et al targeted curcumin against Nsp9 replicase protein [27].…”