Berries, Spices, Citrus: Can You Eat Against Viruses With Scientific Justification

Polyphenols are a huge family of plant molecules (flavonoids, phenolic acids, stilbenes, lignans) that we get from tea, berries, grapes, citrus fruits, and spices. A new review in Nutrients collected dozens of studies and showed that these compounds affect viruses at different stages - they interfere with penetration, inhibit assembly and replication, and shift the immune response toward antiviral "cleansing." But there is an important "but": in a test tube, the effects look powerful, but in humans, they are rarely confirmed - we are limited by bioavailability, doses, and the design of clinical trials.

Background

Viral infections, from seasonal influenza and rotaviruses to herpesviruses, hepatitis, and most recently SARS-CoV-2, remain a major burden on healthcare systems. The arsenal of direct antiviral agents is limited and targeted: many drugs target a single protein of a specific virus, creating a risk of drug resistance and a “bottleneck” in effectiveness. Vaccines save lives, but do not cover all pathogens and all age/clinical groups, and severe forms of the disease are often determined not so much by “purely” viral replication as by dysregulated inflammation and oxidative stress in tissues. Against this background, interest is growing in molecules with a broad spectrum of action and combination pharmacology.

Plant polyphenols are a large family of natural compounds (flavonoids, phenolic acids, stilbenes, lignans) that plants use as their own protective agents. They are of interest to humans for three reasons at once. Firstly, many polyphenols directly interfere with the life cycle of viruses: they interfere with attachment/entry (interaction of membrane proteins with cell receptors), inhibit viral enzymes (proteases, polymerases, neuraminidase) and disrupt the assembly of virions. Secondly, they reconfigure the immune response - reduce hyperinflammation (NF-κB, AP-1), activate the antioxidant program (Nrf2), support antiviral interferon pathways - that is, they also work as tissue cytoprotectors. Thirdly, these are substances that are already present in food (tea, berries, citrus fruits, grapes, olive and spice extracts), which makes them attractive candidates for prevention and adjuvant therapy.

At the same time, the field faces typical “translation” barriers. Most effects have been demonstrated in vitro at micromolar concentrations, whereas in the body, polyphenols are rapidly metabolized and conjugated, their free levels are low, and the activity depends on the form, matrix, and gut microbiota. Extracts are complex mixtures: the composition varies by variety, season, and technology, which makes standardization difficult. There are still few randomized clinical trials; pharmacokinetics, markers of target tissue penetration, and clear therapeutic windows (prevention vs. early therapy) are often lacking. There is also a question of safety/interactions: high doses or concentrates can affect drug-metabolizing enzymes and, under certain conditions, exhibit prooxidant properties.

It is in this context that review papers appear that bring together disparate data into a single map: which polyphenols - against which viruses - through which targets, where the effects are limited to a test tube, and where there are already in vivo and clinical signals; which delivery forms (nanoparticles, liposomes, mucosal sprays) increase bioavailability; where it is more logical to look for synergy with approved antiviral drugs and vaccines. The goal is to move from the general thesis "tea and berries are useful" to precision nutraceuticals: standardized compositions, clear doses/regimes, validated biomarkers of action and rigorous testing at clinically significant endpoints.

What polyphenols can do against viruses

• Block the entry of the virus into the cell. Individual molecules interfere with interaction with receptors (for example, ACE2 and S-RBD in SARS-CoV-2) or disrupt membrane “docking” - a classic example for EGCG and theaflavins from tea.
• Inhibit key replication enzymes. Tannic acid, benserazide and exifone have shown activity against the 3CLpro protease; modulation of RdRp and other viral proteins has been described for a number of polyphenols.
• Reduce inflammation and oxidative stress. Many compounds activate NRF2, reduce NF-κB/AP-1 and cytokines - this may reduce tissue damage during infection.

Now let's talk more specifically about "who's against whom." The review covers a wide range of viruses - from coronaviruses and influenza to hepatitis, herpes viruses, dengue and rotavirus - and summarizes which polyphenols work for what purposes.

Examples where there are already mechanical hooks

• SARS-CoV-2: Tannic acid and benserazide inhibit 3CLpro; quercetin in cell cultures reduces replication by reducing ACE2 and Spike expression and preventing syncytia formation. Pseudoviral models confirm effects on entry.
• Influenza virus: Extracts rich in chlorogenic acid, luteolin and tricine inhibited neuraminidase activity and early steps of replication; effects against H1N1/H3N2 in cells were shown.
• HBV/HCV: Resveratrol reduced HBV replication via the SIRT1-NRF2 axis and antioxidant pathways; EGCG and theaflavins interfered with HCV entry, and tannins interfered with early cellular transmission.
• Herpesviruses: Chlorogenic acid from date extracts blocked HSV-1 adhesion; quercetin reduced viral load in a dose-dependent manner.
• Dengue: Lithospermic acid from Lithospermum erythrorhizon interferes with the expression of viral proteins E and NS3; several plant extracts inhibit entry and post-entry replication.
• Rotavirus: Quercetin (in vitro and in mice) reduced titers and expression of viral proteins in the small intestine; the effect was associated with suppression of early NF-κB activation.

A nice bonus of the review is a summary table by “who/where/how”: virus → polyphenol → model → mechanism → concentrations. For example, there is a spray with curcumin (SARS-CoV-2 and flu), polyphenol-rich extracts (sage, or Ilex ), tannic acid and theaflavin-3,3′-digallate. This is convenient as a map for future preclinical tests.

What's stopping 'tea and spices' from being turned into antiviral drugs

• Bioavailability, bioavailability and once again... Most of the effects were obtained on cell models at micromolar concentrations, "underachievable" by regular nutrition. Without delivery forms (nanoparticles, liposomes), chemical modifications and pharmacokinetics in humans - this will remain "on paper".
• Complex mixtures instead of a single molecule. A real extract has dozens of components; sources, storage, and extraction methods change composition and potency. Standardization is critical.
• The in vitro → clinical divide. Strong activity in cells does not mean clinical benefit: carefully designed RCTs with adequate doses, biomarkers, and endpoints are needed.

Where the "practical light" is already visible

• Prophylactic forms for mucous membranes. Aerosol/spray with curcumin showed antiviral and anti-inflammatory activity in epithelial cultures; it is logical to test it as an adjuvant of barrier protection.
• Combinations with classic drugs. The same theaflavins and EGCG affect the entry and neutralize a number of strains; as auxiliary agents to antivirals (or vaccine protection), they potentially enhance the response.
• Dietary sources with a "narrow" focus. Aronia, pomegranate, licorice are not a panacea, but they provide concentrates with reproducible activity against respiratory and enteroviruses; the question is in the dose and carrier.

Perhaps the authors' main conclusion sounds sober: polyphenols are not "natural oseltamivir", but they are a rich library of molecules with real points of attack on viruses and with immunomodulatory "bonuses". To turn them into therapy, "bridges" are needed - pharmacokinetics in humans, delivery forms, preclinical studies on animals and, finally, RCTs. In the meantime, a reasonable strategy is to obtain polyphenols from a variety of foods (tea, berries, fruits, vegetables, nuts, spices) and consider concentrates as candidates for adjuvant prophylaxis/therapy, and not as a replacement for drugs.

What does this mean for the reader?

• A wide plate is better than a "miracle capsule". Different classes of polyphenols "hit" different targets - a diet with tea/berries/citrus fruits/greens/spices provides a basic background on which the immune system works more reliably.
• Supplements - only for the case. Extracts with "powerful in vitro activity" do not equal proven clinical benefit. If considering concentrates - discuss with your doctor, especially if you have chronic diseases and are taking medications.
• The future is smart delivery. Nanoforms and liposomes can deliver the right doses to the tissues where the outcome of an infection is decided. This field is now growing rapidly.

Source: Coşkun N. et al. Polyphenols as Antiviral Agents: Their Potential Against a Range of Virus Types. Nutrients 17(14):2325, July 16, 2025. Open access. https://doi.org/10.3390/nu17142325