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

Marzouk et al., BIO Web of Conferences, doi:10.1051/bioconf/202519804002, Dec 2025
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In silico and in vitro study showing that turmeric (Curcuma longa) extract inhibits SARS-CoV-2 D614G virus-like particle entry in Vero E6 cells. Authors identified 24 bioactive compounds from turmeric extract using LC-HRMS analysis, with cyclobisdemethoxycurcumin and curcumin showing the strongest binding affinity to the SARS-CoV-2 spike protein (-7.035 and -6.258 kcal/mol, respectively). Molecular dynamics simulations confirmed stable binding interactions over 20 nanoseconds. In vitro experiments demonstrated that turmeric extract significantly inhibited viral entry at low concentrations (2.5-5 μg/mL), while higher concentrations (10-20 μg/mL) showed reduced antiviral activity likely due to cytotoxic effects. The extract maintained cell viability above 70% at all tested concentrations. Authors conclude that turmeric compounds interfere with spike protein function and prevent viral attachment through multiple binding mechanisms.
61 preclinical studies support the efficacy of curcumin for COVID-19:
In silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,1,5,6,11,16,18,24,27 (and specifically the receptor binding domainB,2,4,14,17,20), MproC,4-6,11,13,15-17,19,20,22,25,27,28,30,47, RNA-dependent RNA polymeraseD,4-6,17,26, PLproE,6, ACE2F,2,18,19,21, nucleocapsidG,12,29, nsp10H,29, and helicaseI,35 proteins, and inhibition of spike-ACE2 interactionJ,3. In vitro studies demonstrate inhibition of the spikeA,40 (and specifically the receptor binding domainB,50), MproC,23,40,47,49, ACE2F,50, and TMPRSS2K,50 proteins, and inhibition of spike-ACE2 interactionJ,3,33. In vitro studies demonstrate efficacy in Calu-3L,48, A549M,40, 293TN,7, HEK293-hACE2O,23,38, 293T/hACE2/TMPRSS2P,39, Vero E6Q,1,13,17,27,38,40,42,44,46,48, and SH-SY5YR,37 cells. Curcumin decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells46, alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress7, may limit COVID-19 induced cardiac damage by inhibiting the NF-κB signaling pathway which mediates the profibrotic effects of the SARS-CoV-2 spike protein on cardiac fibroblasts34, 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 variants14, lowers ACE2 and STAT3, curbing lung inflammation and ARDS in preclinical COVID-19 models31, inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity41, has direct virucidal action by disrupting viral envelope integrity43, may inhibit viral replication and modulate inflammatory pathways like NF-κB via SIRT1 activation51, and can function as a photosensitizer in photodynamic therapy to generate reactive oxygen species that damage the virus43.
a. The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.
b. The receptor binding domain is a specific region of the spike protein that binds ACE2 and is a major target of neutralizing antibodies. Focusing on the precise binding site allows highly specific disruption of viral attachment with reduced potential for off-target effects.
c. The main protease or Mpro, also known as 3CLpro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting Mpro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.
d. RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.
e. The papain-like protease (PLpro) has multiple functions including cleaving viral polyproteins and suppressing the host immune response by deubiquitination and deISGylation of host proteins. Inhibiting PLpro may block viral replication and help restore normal immune responses.
f. The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.
g. The nucleocapsid (N) protein binds and encapsulates the viral genome by coating the viral RNA. N enables formation and release of infectious virions and plays additional roles in viral replication and pathogenesis. N is also an immunodominant antigen used in diagnostic assays.
h. Non-structural protein 10 (nsp10) serves as an RNA chaperone and stabilizes conformations of nsp12 and nsp14 in the replicase-transcriptase complex, which synthesizes new viral RNAs. Nsp10 disruption may destabilize replicase-transcriptase complex activity.
i. The helicase, or nsp13, protein unwinds the double-stranded viral RNA, a crucial step in replication and transcription. Inhibition may prevent viral genome replication and the creation of new virus components.
j. The interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor is a primary method of viral entry, inhibiting this interaction can prevent the virus from attaching to and entering host cells, halting infection at an early stage.
k. Transmembrane protease serine 2 (TMPRSS2) is a host cell protease that primes the spike protein, facilitating cellular entry. TMPRSS2 activity helps enable cleavage of the spike protein required for membrane fusion and virus entry. Inhibition may especially protect respiratory epithelial cells, buy may have physiological effects.
l. Calu-3 is a human lung adenocarcinoma cell line with moderate ACE2 and TMPRSS2 expression and SARS-CoV-2 susceptibility. It provides a model of the human respiratory epithelium, but many not be ideal for modeling early stages of infection due to the moderate expression levels of ACE2 and TMPRSS2.
m. A549 is a human lung carcinoma cell line with low ACE2 expression and SARS-CoV-2 susceptibility. Viral entry/replication can be studied but the cells may not replicate all aspects of lung infection.
n. 293T is a human embryonic kidney cell line that can be engineered for high ACE2 expression and SARS-CoV-2 susceptibility. 293T cells are easily transfected and support high protein expression.
o. HEK293-hACE2 is a human embryonic kidney cell line with high ACE2 expression and SARS-CoV-2 susceptibility. Cells have been transfected with a plasmid to express the human ACE2 (hACE2) protein.
p. 293T/hACE2/TMPRSS2 is a human embryonic kidney cell line engineered for high ACE2 and TMPRSS2 expression, which mimics key aspects of human infection. 293T/hACE2/TMPRSS2 cells are very susceptible to SARS-CoV-2 infection.
q. Vero E6 is an African green monkey kidney cell line with low/no ACE2 expression and high SARS-CoV-2 susceptibility. The cell line is easy to maintain and supports robust viral replication, however the monkey origin may not accurately represent human responses.
r. SH-SY5Y is a human neuroblastoma cell line that exhibits neuronal phenotypes. It is commonly used as an in vitro model for studying neurotoxicity, neurodegenerative diseases, and neuronal differentiation.
Marzouk et al., 3 Dec 2025, peer-reviewed, 8 authors. Contact: msdjati@ub.ac.id.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Computational and Experimental Insights into the Antiviral Mechanism of Turmeric ( Curcuma longa ) against SARS-CoV-2 D614G
Hagar Ali Marzouk, Marlita Marlita, Kavana Hafil Kusuma, Yuyun Ika Christina, Aries Soewondo, Sri Rahayu, Nashi Widodo, Muhammad Sasmito Djati
BIO Web of Conferences, doi:10.1051/bioconf/202519804002
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 druglikeness and predicted antiviral activity using PASS Online. Molecular docking was performed using PyRx software by targeting the receptorbinding 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
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DOI record: { "DOI": "10.1051/bioconf/202519804002", "ISSN": [ "2117-4458" ], "URL": "http://dx.doi.org/10.1051/bioconf/202519804002", "abstract": "<jats:p>\n Natural plant-derived compounds are increasingly investigated as potential inhibitors of SARS-CoV-2 infection. Turmeric\n <jats:italic>(Curcuma longa)</jats:italic>\n contains curcumin and other bioactive compounds with reported antiviral, anti-inflammatory, and immunomodulatory properties. However, the inhibitory mechanism of\n <jats:italic>C. longa</jats:italic>\n 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\n <jats:italic>C. longa</jats:italic>\n to inhibit viral entry through integrated\n <jats:italic>in silico</jats:italic>\n and\n <jats:italic>in vitro</jats:italic>\n 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\n <jats:italic>C. longa</jats:italic>\n extract significantly (p &lt; 0.05) inhibited VLP internalization into Vero E6 compared with the untreated control. These findings demonstrate that\n <jats:italic>C. longa</jats:italic>\n 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.\n </jats:p>", "alternative-id": [ "bioconf_ambc2025_04002" ], "author": [ { "affiliation": [ { "name": "Doctoral Program, Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University", "place": [ "Indonesia" ] } ], "family": "Marzouk", "given": "Hagar Ali", "sequence": "first" }, { "affiliation": [ { "name": "Faculty of Mechatronics, Informatics and Interdisciplinary Studies, Technical University of Liberec", "place": [ "Czech Republic" ] }, { "name": "Institute for Nanomaterials, Advanced Technologies and Innovation, Technical University of Liberec", "place": [ "Czech Republic" ] } ], "family": "Marlita", "given": "Marlita", "sequence": "additional" }, { "affiliation": [ { "name": "Doctoral Program, Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University", "place": [ "Indonesia" ] } ], "family": "Kusuma", "given": "Kavana Hafil", "sequence": "additional" }, { "affiliation": [ { "name": "Innovation Center of Integrative Jamu and Eco-pharmaca, Brawijaya University", "place": [ "Indonesia" ] }, { "name": "Dewan Jamu Indonesia East Java Region", "place": [ "Indonesia" ] } ], "family": "Christina", "given": "Yuyun Ika", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University", "place": [ "Indonesia" ] } ], "family": "Soewondo", "given": "Aries", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University", "place": [ "Indonesia" ] } ], "family": "Rahayu", "given": "Sri", "sequence": "additional" }, { "affiliation": [ { "name": "Innovation Center of Integrative Jamu and Eco-pharmaca, Brawijaya University", "place": [ "Indonesia" ] }, { "name": "Dewan Jamu Indonesia East Java Region", "place": [ "Indonesia" ] }, { "name": "Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University", "place": [ "Indonesia" ] } ], "family": "Widodo", "given": "Nashi", "sequence": "additional" }, { "affiliation": [ { "name": "Innovation Center of Integrative Jamu and Eco-pharmaca, Brawijaya University", "place": [ "Indonesia" ] }, { "name": "Dewan Jamu Indonesia East Java Region", "place": [ "Indonesia" ] }, { "name": "Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University", "place": [ "Indonesia" ] } ], "family": "Djati", "given": "Muhammad Sasmito", "sequence": "additional" } ], "container-title": "BIO Web of Conferences", "container-title-short": "BIO Web Conf.", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 12, 4 ] ], "date-time": "2025-12-04T08:44:39Z", "timestamp": 1764837879000 }, "deposited": { "date-parts": [ [ 2025, 12, 4 ] ], "date-time": "2025-12-04T08:45:12Z", "timestamp": 1764837912000 }, "editor": [ { "affiliation": [], "family": "Ni’matuzahroh", "sequence": "first" }, { "affiliation": [], "family": "Lynn", "given": "T.M.", "sequence": "additional" }, { "affiliation": [], "family": "Salamun", "sequence": "additional" }, { "affiliation": [], "family": "Zakaria", "given": "Z.", "sequence": "additional" }, { "affiliation": [], "family": "Sukmawati", "given": "D.", "sequence": "additional" }, { "affiliation": [], "family": "Geraldi", "given": "A.", "sequence": "additional" } ], "indexed": { "date-parts": [ [ 2025, 12, 4 ] ], "date-time": "2025-12-04T08:47:37Z", "timestamp": 1764838057707, "version": "3.46.0" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2025 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 336, "start": { "date-parts": [ [ 2025, 12, 3 ] ], "date-time": "2025-12-03T00:00:00Z", "timestamp": 1764720000000 } } ], "link": [ { "URL": "https://www.bio-conferences.org/10.1051/bioconf/202519804002/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "250", "original-title": [], "page": "04002", "prefix": "10.1051", "published": { "date-parts": [ [ 2025 ] ] }, "published-online": { "date-parts": [ [ 2025, 12, 3 ] ] }, "published-print": { "date-parts": [ [ 2025 ] ] }, "publisher": "EDP Sciences", "reference": [ { "DOI": "10.3389/fphar.2020.578970", "doi-asserted-by": "crossref", "key": "R1", "unstructured": "Ahmad S., Zahiruddin S., Parveen B., Basist P., Parveen A., Gaurav R. 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