Abstract: molecules Article Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms Damariz Marín-Palma 1,2,† , Jorge H. Tabares-Guevara 1,† , María I. Zapata-Cardona 2 , Lizdany Flórez-Álvarez 2 , Lina M. Yepes 2 , Maria T. Rugeles 2 , Wildeman Zapata-Builes 1,2 , Juan C. Hernandez 1,2 and Natalia A. Taborda 1,3, * 1 2 3 * †



 Citation: Marín-Palma, D.; Tabares-Guevara, J.H.; Zapata-Cardona, M.I.; Flórez-Álvarez, L.; Yepes, L.M.; Rugeles, M.T.; Zapata-Builes, W.; Hernandez, J.C.; Taborda, N.A. Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms. Molecules 2021, 26, 6900. https://doi.org/10.3390/molecules 26226900 Academic Editor: Erika Ferrari Received: 14 October 2021 Accepted: 11 November 2021 Published: 16 November 2021 Publisher’s Note: MDPI stays neutral Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, 050012 Medellín, Colombia; bleidy1122@gmail.com (D.M.-P.); jorgetabare@gmail.com (J.H.T.-G.); wildeman.zapatab@campusucc.edu.co (W.Z.-B.); juankhernandez@gmail.com (J.C.H.) Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, UdeA, 050010 Medellín, Colombia; mariaisab5@gmail.com (M.I.Z.-C.); liz.1.florez@gmail.com (L.F.-Á.); linayepes123@gmail.com (L.M.Y.); maria.rugeles@udea.edu.co (M.T.R.) Grupo de Investigaciones Biomédicas Uniremington, Programa de Medicina, Facultad de Ciencias de la Salud, Corporación Universitaria Remington, 050016 Medellín, Colombia Correspondence: natalia.taborda@uniremington.educo These authors contributed equally to this work. 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. Keywords: curcumin; antiviral; COVID-19; SARS-CoV-2; immune response; inflammation; D614G strain; Delta variant with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an..