Computational and Experimental Insights into the Antiviral Mechanism of Turmeric (Curcuma longa) against SARS-CoV-2 D614G

¹ Doctoral Program, Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, Indonesia
² Faculty of Mechatronics, Informatics and Interdisciplinary Studies, Technical University of Liberec, Studentská 1402/2, 461 17 Liberec, Czech Republic
³ Institute for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec, Bendlova 1409/7, 461 17 Liberec, Czech Republic
⁴ Innovation Center of Integrative Jamu and Eco-pharmaca, Brawijaya University, Malang 65145, East Java, Indonesia
⁵ Dewan Jamu Indonesia East Java Region, Malang, East Java, Indonesia
⁶ Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, Indonesia

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Natural plant-derived compounds are increasingly investigated as potential inhibitors of SARS-CoV-2 infection. Turmeric (Curcuma longa) contains curcumin and other bioactive compounds with reported antiviral, anti-inflammatory, and immunomodulatory properties. However, the inhibitory mechanism of C. longa against SARS-CoV-2 D614G viruslike particles (VLPs) has not been fully elucidated. This study aimed to evaluate the potential of the ethanol extract of C. longa to inhibit viral entry through integrated in silico and in vitro approaches. Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) analysis identified 24 major bioactive compounds, which were screened for drug-likeness and predicted antiviral activity using PASS Online. Molecular docking was performed using PyRx software by targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, followed by 20-ns molecular dynamics simulations to evaluate complex stability. For in vitro validation, Vero E6 cells were exposed to SARS-CoV-2 D614G VLPs expressing EGFP reporter and turmeric extract (2.5 and 5 μg/mL). Viral entry was quantified by EGFP fluorescence intensity after 24 h. The results showed that cyclobisdemethoxycurcumin and curcumin showed high binding affinity (-7.035 and -6.258 kcal/mol, respectively) and stable interactions within the RBD binding pocket. Treatment with C. longa extract significantly (p < 0.05) inhibited VLP internalization into Vero E6 compared with the untreated control. These findings demonstrate that C. longa bioactive compounds interfere with SARS-CoV-2 D614G spike-mediated entry. Therefore, it can support their potential as natural antiviral candidates for further in vitro and in vivo investigation.