Dose-dependent antiviral effects of glycyrrhizin, curcumin, and harmaline against clinical SARS-CoV-2 isolates, including D614G, Omicron BA.5, and Omicron XBB.1
et al., BMC Complementary Medicine and Therapies, doi:10.1186/s12906-026-05253-1, Jan 2026
Curcumin for COVID-19
17th treatment shown to reduce risk in
February 2021, now with p = 0.0000000061 from 28 studies.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
In vitro study in A549-AT cells showing that curcumin and glycyrrhizin effectively inhibit SARS-CoV-2 D614G, Omicron BA.5, and Omicron XBB.1 variants, while harmaline effectively inhibits only the Omicron variants, all at subtoxic concentrations.
62 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,4-6,11,13,15-17,19,20,22,25,27,28,30,48 , RNA-dependent RNA polymeraseD,4-6,17,26 , PLproE,6, ACE2F,2,18,19,21 , nucleocapsidG,12,29 , nsp10H,29, and helicaseI,36 proteins, and inhibition of spike-ACE2 interactionJ,3.
In vitro studies demonstrate inhibition of the spikeA,41 (and specifically the receptor binding domainB,51), MproC,23,41,48,50 , ACE2F,51, and TMPRSS2K,51 proteins, and inhibition of spike-ACE2 interactionJ,3,34 .
In vitro studies demonstrate efficacy in Calu-3L,49, A549M,41, A549-ATN,31, 293TO,7, HEK293-hACE2P,23,39 , 293T/hACE2/TMPRSS2Q,40, Vero E6R,1,13,17,27,39,41,43,45,47,49 , and SH-SY5YS,38 cells.
Curcumin decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells47, 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 fibroblasts35, 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 models32, inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity42, has direct virucidal action by disrupting viral envelope integrity44, may inhibit viral replication and modulate inflammatory pathways like NF-κB via SIRT1 activation52, and can function as a photosensitizer in photodynamic therapy to generate reactive oxygen species that damage the virus44.
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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.
A549-AT is a human lung carcinoma cell line stably transfected with ACE2 and TMPRSS2 receptors. Unlike the parental line, this overexpression ensures stable infection and enhanced viral entry, allowing for the evaluation of antiviral efficacy against various SARS-CoV-2 variants.
o.
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.
p.
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.
q.
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.
r.
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.
s.
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.
Grüneberg et al., 22 Jan 2026, Germany, peer-reviewed, 11 authors.
Contact: adalbert.krawczyk@uk-essen.de.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Dose-dependent antiviral effects of glycyrrhizin, curcumin, and harmaline against clinical SARS-CoV-2 isolates, including D614G, Omicron BA.5, and Omicron XBB.1
BMC Complementary Medicine and Therapies, doi:10.1186/s12906-026-05253-1
Background SARS-CoV-2 remains a major global health challenge, as infection can lead to potential lifethreatening conditions such as COVID-19. Emerging variants of the virus are characterized by higher transmission rates and immune escape mutations, enabling them to evade vaccine-induced immunity. Existing treatment options, including monoclonal antibodies, are often variant-specific and not widely accessible, especially in low-and middle-income countries. Natural compounds derived from medicinal herbs and green tea have demonstrated antiviral activity against various viruses and may offer promising, variantindependent therapeutic potential.
Methods In this study, we examined the antiviral activity of four plant-derived compounds: glycyrrhizin, curcumin, harmaline, and (-)-epigallocatechin. The compounds were tested in vitro against SARS-CoV-2 D614G, Omicron BA.5, and Omicron XBB.1. The antiviral efficacy was assessed at subtoxic concentrations to evaluate potential therapeutic applicability.
Results All tested compounds showed effective neutralization of SARS-CoV-2 D614G, Omicron BA.5, and Omicron XBB.1 at subtoxic concentrations. In particular, glycyrrhizin, curcumin, and harmaline exhibited potent antiviral activity across all tested variants.
Conclusions Our findings support the potential of glycyrrhizin, curcumin, and harmaline as variantindependent treatment candidates for COVID-19. However, further clinical studies are necessary to validate their efficacy and safety in vivo.
Declarations Ethics approval and consent to participate The study was approved by the local ethics committee, Ethik-Kommission der Universität Duisburg-Essen (20-9374-BO), and was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent to participate was obtained from all participants.
Consent for publication All authors have read the manuscript in its entirety and consent to its submission and publication in the present form.
Competing interests The authors declare that they have no competing interests.
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