The central mechanism is shared across all applications. A photosensitizer — a molecule that absorbs light of a specific wavelength — is exposed to matching illumination in the presence of molecular oxygen, producing reactive oxygen species such as singlet oxygen that inflict oxidative damage on viral lipids, proteins and nucleic acids. Unlike conventional antivirals that inhibit a single molecular target, this multi-target oxidative assault makes the development of resistance theoretically less likely. The review explicitly separates two applications that are often conflated: photodynamic inactivation, or PDI, which destroys viruses in ex vivo matrices such as blood products, water and surfaces, and photodynamic therapy, or PDT, which treats viral infections or lesions in living organisms. The distinction matters because the translational prospects of the two are very different.

The most striking pattern in the dataset is structural. Enveloped viruses — those carrying a host-derived lipid membrane studded with glycoproteins — proved consistently susceptible to photodynamic killing. Studies of HIV-1, for example, showed that methylene blue at 1 micromolar concentration, activated with 620–670 nm light, achieved greater than 6.3 log10 reductions in infectivity within ten minutes, with cross-linking of the gp120 envelope glycoprotein, structural alterations of the p24 capsid, degradation of viral RNA and complete inhibition of reverse transcriptase, all strictly dependent on light exposure. The silicon phthalocyanine Pc4 achieved at least 5.5 log10 reductions of HIV in red blood cell concentrates at 670–680 nm with 18–40 J/cm², with hemolysis below 1 percent after extended storage.

Similar potency emerged across other enveloped families. Vesicular stomatitis virus, a common surrogate for enveloped RNA viruses, was reduced by more than 5 log10 in every one of seven included studies, using photosensitizers ranging from methylene blue and aluminum phthalocyanine tetrasulfonate to fullerenes and dimethylmethylene blue, at light doses from 1 to 120 J/cm². Mechanistic work identified singlet oxygen as the dominant damaging species through oxygen-dependence experiments and quenching studies. Notably, one study found that lower fluence rates — 10 versus 50 mW/cm² at matched total fluence — were paradoxically associated with greater VSV inactivation, but the authors of that study rejected simple oxygen depletion as an explanation and proposed alternative photochemical pathways, and the effect has not been consistently replicated. Strategies to protect blood cells during treatment also advanced: combining dimethylmethylene blue with quinacrine achieved more than 5 log VSV inactivation while reducing hemolysis from roughly 20 percent to 5 percent.

Coronavirus data, though limited to three studies, followed the same envelope-centric logic. Hydrophobic Rose Bengal alkyl esters activated at 520 nm with 6 J/cm² showed sub-nanomolar effective concentrations against SARS-CoV-2 in Vero cells, with exceptionally high selectivity indices — but no activity against non-enveloped viruses, implicating lipid membrane damage as the dominant mechanism. Methylene blue at 1 micromolar with 660 nm light at 1 J/cm² produced greater than four log10 reductions in SARS-CoV-2 pseudovirus transduction, with the combined treatment showing synergy with UV-C and oxygen dependence supporting a type II photochemical mechanism. The ruthenium compound TLD-1433, illuminated at 525 nm with 45 J/cm², inactivated more than 90 percent of human coronavirus OC-43 within seconds at low nanomolar concentrations, acting chiefly through lipid peroxidation — although its performance declined markedly in protein-rich or turbid matrices.

Herpesviruses and mosquito-borne enveloped RNA viruses showed comparable vulnerability. Cationic vinyl-substituted porphyrins achieved greater than 99 percent plaque reduction of HSV-1 at 0.5–1 micromolar with 5 J/cm² at 630 nm, with efficacy tracking the number of hydrophobic vinyl substituents. Zinc phthalocyanine conjugated to IgY antibodies completely inactivated bovine herpesvirus 1 in artificially infected bovine semen while preserving sperm motility, and TLD-1433 and Rose Bengal derivatives rapidly inactivated Zika and Chikungunya viruses at nanomolar concentrations. By contrast, non-enveloped viruses proved far more stubborn. Adenovirus type 5 and mammalian orthoreovirus required micromolar TLD-1433 concentrations and prolonged irradiation of up to 720 J/cm² to yield measurable infectivity reductions, and rotaviruses needed riboflavin activated by simulated sunlight at cumulative fluences up to 100 J/cm² in water. The dense protein capsids of these viruses lack the lipid membrane that photosensitizers attack most efficiently, though the review cautions that envelope status is not a universal rule — matrix composition, photosensitizer localization and aggregation state may matter at least as much.

The clinical evidence base is small and mixed. One randomized crossover trial in twelve healthy volunteers who received methylene blue-treated plasma reported no serious adverse events or significant laboratory changes, providing early human safety data for pathogen-reduced plasma — but not evidence that antiviral PDT is safe or effective when administered to infected patients. A pediatric case report described complete resolution of HSV-1–associated erythema multiforme major within seven days after methylene blue-mediated PDT with 660 nm LED light at 10 J/cm². The review also cites limited studies of localized lesions, including ALA-PDT for HPV-related cervical lesions with reported regression rates of 90–95 percent and HPV clearance of 67.5 percent, combination PDT after excision of condylomata with zero recurrence versus 33.3 percent with trichloroacetic acid, and preliminary intranasal PDT for mild COVID-19 with PCR negativity within 4–7 days. These reports are heterogeneous and frequently small, so they should be read as signals warranting further trials rather than established efficacy.

Several caveats temper the safety picture. Methylene blue treatment of plasma, while efficiently destroying enveloped viruses, reduced factor VIII activity by 30–36 percent and fibrinogen by 15–40 percent, and the balance between viral kill and preservation of labile blood components remains a central engineering challenge. Organic matter — serum proteins, mucin, wastewater solids — scavenges reactive oxygen species and attenuates efficacy, meaning protocols must be tailored to each viral target and matrix. Photophysical parameters are chronically underreported: risk of bias assessment found incomplete light parameter reporting in 10 of 30 studies and lack of blinding in 14, although 18 studies rated low risk of bias in at least four of six domains and sensitivity analyses did not change the main conclusion about envelope-dependent susceptibility. The review also was not prospectively registered, a limitation the authors acknowledge may introduce selective reporting risk, mitigated by a priori definitions of all search and eligibility criteria.

The review’s most consequential boundary statement is stark: current evidence does not support conventional PDT as a clinically feasible treatment for systemic viremia. Treating viruses circulating in the bloodstream would require whole-body irradiation or invasive light delivery to internal organs, neither feasible nor safe with current technology, and systemic photosensitizer administration risks generalized phototoxicity. All efficacy claims therefore apply strictly to in vitro models, localized accessible infections and ex vivo blood product processing. The authors point to possible future directions — extracorporeal light-delivery devices, nanoparticle-based photosensitizer carriers, type I photosensitizers that generate radical species with reduced oxygen dependence for hypoxic tissues, and combinations with antivirals such as acyclovir — but stress that none has been clinically validated. They also note that some drug-resistant strains, including acyclovir-resistant HSV-1, may resist conventional photosensitizers. Their bottom line is that the most realistic antiviral applications remain exactly where the strongest evidence already sits: decontaminating blood products and treating localized mucocutaneous infections, with rigorous clinical trials still needed before broader claims can be made.

Subject of Research: Antiviral efficacy and translational limits of photodynamic inactivation and photodynamic therapy against viral pathogens

Article Title: Photodynamic inactivation and photodynamic therapy for viral pathogens: a systematic review of antiviral efficacy, mechanisms, and translational boundaries

Article References: Alikhani, M. S., Farmani, A., Teimoori, A., Dosti-Irani, A., Sadrzadeh-Afshar, M.-S., & Fekrazad, R. (2026). Photodynamic inactivation and photodynamic therapy for viral pathogens: a systematic review of antiviral efficacy, mechanisms, and translational boundaries. International Microbiology. https://doi.org/10.1007/s10123-026-00915-z

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DOI: 10.1007/s10123-026-00915-z

Keywords: photodynamic inactivation, photodynamic therapy, photosensitizers, enveloped viruses, methylene blue, reactive oxygen species, blood product decontamination, SARS-CoV-2, HIV, herpesviruses, systematic review, antiviral

Across the available studies, post-exposure prophylaxis, or PEP, was associated with relative risk reductions of 57–86% in household influenza outcomes compared with control regimens, while index-patient treatment was associated with more modest relative risk reductions of 24–29%. The review examined two distinct ways in which baloxavir could be used to limit influenza transmission within households. In the index-patient strategy, an infected person receives baloxavir with the aim of reducing infectiousness and onward transmission to household contacts.

In the PEP strategy, contacts already exposed to the index patient receive the antiviral to prevent infection from becoming established. The studies assessed laboratory-confirmed or symptomatic influenza among contacts, using comparisons that included placebo or neuraminidase inhibitors. The investigators searched PubMed, Embase, Web of Science and the Cochrane Library for randomized and observational studies published or indexed from 1 January 2018 through 25 June 2025.

The largest estimated effects were reported for PEP. Across the included evidence, giving baloxavir to exposed household contacts was associated with relative risk reductions ranging from 57% to 86% in household influenza outcomes. These results support a larger estimated protective association for PEP than for treating infected household members alone.

Evidence for index-patient treatment was less pronounced. Baloxavir treatment of infected individuals was associated with relative risk reductions of 24–29% in household transmission outcomes, indicating a smaller estimated indirect effect than the range reported for PEP. One outcome—a 24% reduction in symptomatic transmission measured five days after treatment—did not reach statistical significance, with P = 0.16.

The review therefore described baloxavir-based strategies as potentially useful for reducing household influenza transmission while distinguishing the more modest and, in that five-day result, statistically uncertain findings for index-patient treatment.

Subject of Research: Baloxavir-based strategies for reducing influenza transmission within households

Article Title: Effectiveness of baloxavir marboxil in reducing household influenza transmission: a systematic review

Article References: Niu, B., Wu, G., Chen, R., Zhang, W., Yuan, Z., Bai, Y., & Du, Z. (2026). Effectiveness of baloxavir marboxil in reducing household influenza transmission: a systematic review. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14294-3

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DOI: 10.1186/s12879-026-14294-3

Keywords: baloxavir marboxil, influenza, household transmission, post-exposure prophylaxis, index-patient treatment, antiviral, systematic review, CENTERSTONE trial, Japan, Effectiveness, baloxavir, marboxil

Anthocyanins are glycosylated forms of anthocyanidins, built on a flavylium ion backbone with a C6-C3-C6 carbon structure: a 15-carbon skeleton of two aromatic rings connected by a three-carbon bridge forming a heterocyclic ring. Six major anthocyanidins—petunidin, malvidin, peonidin, cyanidin, delphinidin, and pelargonidin—account for roughly 90 percent of those found in nature. Beyond their role as plant pigments, these compounds exhibit antioxidant, anti-inflammatory, neuroprotective, and anticancer activities, and previous work has documented broad-spectrum antiviral effects against several RNA viruses, including suppression of influenza neuraminidase.

The review identifies the SARS-CoV-2 main protease, Mpro, as the most extensively investigated molecular target. Because Mpro cleaves viral polyproteins into functional units required for replication and maturation—and because its structure differs substantially from any human protease—it has become one of the most attractive antiviral targets against COVID-19. Numerous independent molecular docking studies have demonstrated favorable predicted interactions between structurally diverse anthocyanins and the Mpro catalytic site, particularly the catalytic residues His41 and Cys145, with no clear cellular cytotoxicity reported. Notably, polyacylated anthocyanins such as tecophilin, cyanodelphin, gentiodelphin, and phacelianin consistently exhibited stronger predicted binding than diacylated or monomeric forms, suggesting that structural modification may enhance inhibitory activity.

Several studies have begun to provide experimental validation of these computational predictions. Cyanidin-3-O-sambubioside isolated from kokum fruit demonstrated approximately 79 percent inhibition of Mpro activity at 100 micromolar in an in vitro enzymatic assay, with favorable docking to the catalytic dyad and no cytotoxicity to BEAS-2B cells. Cyanidin 3-O-galactoside from cranberry showed potent Mpro inhibition with an IC50 of 9.98 micromolar in FRET-based enzymatic assays, while whole cranberry anthocyanin extracts achieved an IC50 of 23.58 micrograms per milliliter. More recently, a high-resolution mass spectrometry-based screening platform identified delphinidin-3-glucoside from blueberry as a covalent Mpro inhibitor, producing dose-dependent inhibition of SARS-CoV-2 replication in Vero E6 cells with an IC50 of approximately 35.8 micromolar—comparable to the established Mpro inhibitor baicalin.

Beyond Mpro, anthocyanins have been proposed to interact with other viral replication proteins, particularly the RNA-dependent RNA polymerase and helicase. A comprehensive virtual screening of naturally occurring polyphenols identified cyanidin-3-O-rutinoside, petunidin-3,5-O-diglucoside, and delphinidin-3-O-rutinoside as the strongest predicted RdRp inhibitors, with binding energies exceeding those of remdesivir. A multitarget docking study found that cyanidin 3-O-glucosyl-rutinoside bound strongly across Mpro, RdRp, and helicase simultaneously. However, the review notes that no studies have conclusively demonstrated direct enzymatic or structural inhibition of these proteins, and the available evidence remains largely limited to computational predictions.

Anthocyanins may also interfere with viral entry by disrupting the interaction between the spike glycoprotein receptor-binding domain and the host ACE2 receptor. In the large-scale multitarget docking study, cyanidin 3-O-glucosyl-rutinoside demonstrated the strongest predicted interactions with both spike protein and ACE2, with docking scores of -10.07 and -13.26 respectively, outperforming the reference compounds remdesivir and hydroxychloroquine. Additional anthocyanins, including pelargonidin-3-rhamnoside and cyanidin-7-arabinoside, were predicted to bind favorably to the spike receptor-binding domain. The review emphasizes, however, that experimental evidence supporting this entry-blocking mechanism remains scarce and should currently be regarded as computational prediction requiring biochemical and cell-based validation.

The review also highlights a complementary mechanism: modulation of host inflammatory responses. Excessive cytokine activation is associated with COVID-19 severity and tissue damage. Using an in vitro model of SARS-CoV-2 spike protein S1-induced inflammation, black rice germ and bran extract rich in cyanidin-3-O-glucoside and peonidin-3-O-glucoside significantly suppressed expression of the inflammatory genes NLRP3, IL-1β, and IL-18, while reducing secretion of IL-6, IL-1β, and IL-18 in A549 lung epithelial cells and THP-1 macrophages. The extract was effective at 12.5 to 100 micrograms per milliliter, with purified constituents active at 1.25 to 10 micrograms per milliliter, operating through inhibition of the NF-κB/NLRP3 inflammasome signaling pathway.

Evidence from anthocyanin-rich plant extracts adds further complexity. Standardized European black elderberry fruit extract, containing 4.6 percent total polyphenols and 3.5 percent anthocyanins, demonstrated in vitro antiviral activity against the original Wuhan strain and the Alpha, Beta, Gamma, Delta, and Omicron variants, with cyanidin-3-sambubioside-5-glucoside exhibiting the strongest inhibition among major components. A subsequent study found that combining elderberry extract standardized to 3.2 percent anthocyanins with quinine produced synergistic antiviral effects against SARS-CoV-2 in Calu-3 lung cells, with a Bliss independence score of 27.8. The review cautions that because extracts contain multiple polyphenols and other phytochemicals, the relative contribution of anthocyanins alone cannot be determined with certainty.

Despite encouraging computational and preclinical evidence, the review identifies poor physicochemical stability and low bioavailability as major translational challenges. Only approximately 2 percent of ingested anthocyanins are reported to retain their intact C6-C3-C6 structure after ingestion. These compounds are highly susceptible to degradation by pH, temperature, oxygen, and light—under acidic conditions they exist predominantly as the red flavylium cation, whereas neutral and alkaline environments promote quinonoidal base formation, reducing both stability and biological activity. Such degradation may occur during food processing, storage, gastrointestinal digestion, and systemic absorption, potentially limiting the concentrations required to achieve the antiviral effects observed in vitro.

Several strategies are being explored to overcome these limitations. Structural modification through glycosylation and acylation, physical protection through microencapsulation and nanoencapsulation, stabilization via complex formation with macromolecules, and co-pigmentation techniques all aim to preserve structural integrity and enhance systemic availability. Encapsulation technologies coat extracted bioactive compounds with protective materials—typically GRAS-classified biopolymers composed of proteins, carbohydrates, or their combinations—to shield them from extreme environments within the body and allow them to reach the small intestine intact. Nanoparticles are of particular interest because their high surface-area-to-volume ratio can enhance stability, solubility, and bioavailability while providing more reactive sites for interaction. The review concludes that while anthocyanins represent promising natural compounds for further antiviral investigation, additional mechanistic studies, in vivo validation using animal models, comprehensive pharmacokinetic evaluations, and well-designed clinical trials are required before their clinical potential against COVID-19 can be established.

Subject of Research: Anthocyanins as potential SARS-CoV-2 antivirals: mechanisms, evidence, and translational challenges

Article Title: Antiviral potential of anthocyanins against SARS-CoV-2: current evidence, translational challenges, and future perspectives

Article References: Lu, P. (2026). Antiviral potential of anthocyanins against SARS-CoV-2: current evidence, translational challenges, and future perspectives. Frontiers in Virology, 6, Article 1897871. https://doi.org/10.3389/fviro.2026.1897871

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DOI: 10.3389/fviro.2026.1897871

Keywords: anthocyanins, SARS-CoV-2, COVID-19, antiviral, flavonoids, Mpro, RdRp, ACE2, bioavailability, elderberry, potential, against

The motivation behind the work lies in a well-known weakness of current influenza therapy. Drugs such as oseltamivir, zanamivir and peramivir all target neuraminidase, one of the two surface glycoproteins of the influenza virus, and single amino acid substitutions in that protein can render them ineffective. Influenza type A, the subtype responsible for pandemics since 1918, remains the most clinically significant of the influenza types, and the fragility of neuraminidase-targeted treatment has pushed researchers toward alternative targets and alternative chemical scaffolds. Hemagglutinin, the second surface glycoprotein, offers such a target: it carries the receptor-binding site that recognizes sialic acid on host cells and the fusion machinery that delivers the viral genome inside. Natural products, long valued as a reservoir of bioactive molecules including saponins, flavonoids, coumarins and stilbenoids, have repeatedly yielded compounds that interfere with viral proteins, and the authors set out to test whether thyme’s principal essential-oil constituents could do the same to hemagglutinin.

Thymus vulgaris, a woody member of the mint family native to southern Europe and the western Mediterranean, has a long history of medicinal use as an antiseptic, antimicrobial and tonic. Gas chromatography–mass spectrometry analyses of its essential oil identify five dominant constituents whose proportions vary widely between chemotypes: thymol, ranging from 6.7 to 66.10 percent; linalool, from 1.36 to 22.25 percent; carvacrol, from 2.33 to 20.03 percent; α-terpineol, from 0.15 to 11.61 percent; and geraniol, from 0.32 to 11.31 percent. Thymol and carvacrol are monoterpene phenols, linalool is a monoterpene alcohol, and all three have documented anti-inflammatory, antimicrobial and antioxidant activity. Curcumin, the polyphenolic yellow pigment of Curcuma longa, was included as a comparator because of its extensive literature on antiviral and anti-inflammatory effects, even though its clinical translation has been hampered by poor bioavailability and chemical instability.

The computational strategy rested on an atomistic model of the H1N1 hemagglutinin trimer, taken from the Protein Data Bank under entry 3LZG. The trimeric form is the biologically relevant prefusion assembly: each protomer consists of an HA1 chain forming the globular receptor-binding head and an HA2 chain containing the membrane-fusion stalk. The receptor-binding site sits at the distal tip of HA1 and is built from three structural elements—the 130-loop, the 190-helix and the 220-loop. Simulating the intact trimer matters because models that omit the trimeric interface cannot capture conformational stability, allosteric coupling between protomers, or the large-scale rearrangements that hemagglutinin undergoes when triggered by low pH to fuse viral and cellular membranes. The team therefore ran all-atom simulations in GROMACS 5.1.4 using the GROMOS54A7 force field, the SPC water model, a Nosé-Hoover thermostat at physiological temperature and a Berendsen barostat at 1 bar, with particle-mesh Ewald summation for electrostatics and a 1.2-nanometer cutoff for Lennard-Jones interactions.

Each simulation placed the hemagglutinin trimer in a cubic box seven nanometers on a side, solvated it, neutralized it and introduced three copies of one ligand at a concentration of 14 millimolar. Using multiple ligand molecules rather than a single one allowed the researchers to observe whether adsorption occurs competitively and which sites on the protein surface are preferred. After energy minimization, each system was equilibrated for 20 nanoseconds in the canonical ensemble and a further 20 nanoseconds under constant pressure, before a production run of 100 nanoseconds whose final 10 nanoseconds were analyzed in detail. Binding energies were decomposed with the MM-PBSA method, and the trajectories were visualized with VMD. Complementing the dynamics, density functional theory calculations at the B3LYP/6-31G(d,p) level in the GAMESS program yielded optimized geometries, HOMO and LUMO energies, dipole moments and polarizabilities, with partial atomic charges fitted to the electrostatic potential in an aqueous environment to mimic the biological milieu.

The docking-like outcome of the dynamics was striking in its site selectivity. Starting from random positions in the solvent, carvacrol and linalool both migrated to and adsorbed onto the 190-helix of HA1, a structural element that contributes directly to receptor binding, and onto the fusion-related stalk region of HA2. Thymol bound to the fusion-related stalk of HA2. Curcumin, by contrast, ended up at a site involving no functionally important residues. The energetic decomposition explained the difference. Thymol achieved the strongest Lennard-Jones interaction with the protein at −231.42 kJ/mol and the highest overall binding energy at −360.56 kJ/mol, followed by linalool at −351.21 kJ/mol and carvacrol at −229.71 kJ/mol. Curcumin’s binding energy of −167.28 kJ/mol was the weakest of the four, with both its dispersive and electrostatic contributions substantially smaller. Thymol also formed more hydrogen bonds with hemagglutinin than any other ligand tested.

Conformational analysis reinforced the picture. Relative to hemagglutinin in pure water, the root mean square deviation of the protein increased after adsorption of every thyme constituent, with thymol producing the largest structural drift, whereas curcumin’s trajectory closely resembled the ligand-free reference. Root mean square fluctuation profiles showed that the thyme compounds perturbed residues in both the receptor-binding HA1 head and the fusion-related HA2 stalk, while curcumin left the fluctuation pattern essentially unchanged. The radius of gyration, nearly constant between water and the curcumin-bound system at roughly 7.9 to 8.1 nanometers, decreased significantly when the thyme compounds adsorbed, indicating a more compact protein. Secondary-structure analysis added a further signature: thyme constituents reduced beta-sheet content and increased coil structures, whereas curcumin left the secondary structure largely intact. The thyme compounds also raised the protein’s solvent-accessible surface area and its number of hydrogen bonds with water—thymol lifted the hydrogen-bond count from 5623 to 5817—evidence that they remodel both the fold and the solvation shell of hemagglutinin.

Quantum chemical descriptors and pharmacokinetic screening filled in the electronic and drug-likeness context. Curcumin showed the smallest HOMO-LUMO band gap, 0.12263 Hartree, together with the largest dipole moment and polarizability, consistent with easier electron transfer and higher intrinsic reactivity; the three thyme compounds clustered at higher band gaps between 0.21645 and 0.23092 Hartree with lower polarizabilities. Yet the simulations showed that this electronic reactivity did not translate into stronger protein binding. On the pharmacokinetic side, linalool, thymol and carvacrol fully satisfied Lipinski’s Rule of Five, with molecular weights near 150 g/mol, single hydrogen-bond donors and acceptors, and log P values below 3.3, while curcumin violated one criterion with six hydrogen-bond acceptors, echoing its known bioavailability problems. None of the four compounds was predicted to be mutagenic or tumorigenic by the SwissADME toxicity models.

The authors are careful to frame the findings as computational hypotheses rather than therapeutic claims. Molecular dynamics and quantum mechanics offer atomic-resolution insight into binding geometry, energetics and conformational change, but phytochemical effects are notoriously context-dependent across in vitro, in vivo and clinical settings, and the study’s own limitations—a small number of ligand molecules per box and a 100-nanosecond timescale without an explicit viral membrane—leave room for refinement. Even so, the convergence of strong binding energies, occupation of the receptor-binding helix and the fusion stalk, drug-like physicochemical profiles and demonstrable structural destabilization makes the thyme constituents, and thymol above all, credible leads for experimental follow-up. Biochemical binding assays, antiviral testing in cell culture and ultimately in vivo studies will determine whether the simulated disruption of hemagglutinin can be reproduced where it matters: in a infected host, at the first step of the influenza life cycle.

Subject of Research: Computational evaluation of Thymus vulgaris constituents and curcumin as inhibitors of influenza H1N1 hemagglutinin

Article Title: Evaluating the antiviral potential of Thymus vulgaris constituents and curcumin against influenza hemagglutinin: A molecular dynamics study

Article References: Kordzadeh, A., Hosseinzade, Z., Hadi, A., & Ghaderi, S. (2026). Evaluating the antiviral potential of Thymus vulgaris constituents and curcumin against influenza hemagglutinin: A molecular dynamics study. Results in Chemistry, 31, Article 103943. https://doi.org/10.1016/j.rechem.2026.103943

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DOI: 10.1016/j.rechem.2026.103943

Keywords: influenza, hemagglutinin, Thymus vulgaris, thymol, carvacrol, linalool, curcumin, molecular dynamics, quantum chemistry, antiviral, drug discovery, natural products

What makes marine carbohydrates so chemically interesting is their structural diversity. Polysaccharides extracted from seaweeds, sponges, shellfish and marine bacteria can carry sulfate groups in patterns that differ from species to species, form glycosidic linkages that are uncommon in terrestrial plants, and adopt branched architectures that change how they interact with biological targets. Fucoidans from brown algae, carrageenans from red algae, chitin and chitosan derivatives from crustacean shells, and sulfated glycosaminoglycan-like molecules from marine animals all fall into this category. Because the precise arrangement of sulfate groups and sugar units determines how these molecules bind to proteins, enzymes and cell surfaces, even subtle structural differences can translate into dramatically different biological effects.

That sensitivity to structure is precisely why these molecules have attracted attention across so many therapeutic areas. The review documents reported antiviral, anticoagulant, immunomodulatory and antitumor activities for marine-derived carbohydrates and their derivatives, alongside material properties that make them useful in drug delivery systems, wound dressings and tissue engineering scaffolds. Sulfated polysaccharides, for example, can interfere with viral attachment and entry by mimicking the charged surfaces that viruses normally latch onto, while alginate-based materials have become mainstays in encapsulation and wound-care applications because of their gentle gelling behavior and biocompatibility.

The clinical story of marine-inspired drugs is older than many readers might expect. The review’s authors anchor their timeline to cytarabine, an antileukemia drug approved in the United States in 1969, which traces its chemical inspiration to nucleosides originally isolated from a Caribbean sponge. Although cytarabine is not itself a carbohydrate in the polysaccharide sense, it established a crucial precedent: molecules derived from marine organisms could survive the full gauntlet of preclinical testing, regulatory scrutiny and clinical use. Later products built on alginate, carrageenan and other marine raw materials followed, extending the family of carbohydrate-based medicines into areas such as wound management, drug formulation and symptomatic treatment.

Today, the pipeline is broader than ever. The review surveys clinical-stage candidates derived from marine carbohydrates currently being evaluated for viral infections, cancer, metabolic disorders, tissue repair, cystic fibrosis and neurological disease. This breadth reflects both the versatility of the molecules and the maturity of the field: what was once a collection of exploratory extracts has become a portfolio of defined candidates moving through controlled trials. Yet the authors are careful to note that the distance between a promising laboratory result and an approved product remains substantial, and that the obstacles are not primarily about discovering new activities.

The central challenge, according to the review, is reproducibility. The biological activity of a marine polysaccharide depends on its molecular weight, its sulfation pattern and its monosaccharide composition, but all three of these parameters can vary with the species from which the material is harvested, the season in which it is collected, and the extraction and processing methods used to isolate it. A batch of fucoidan gathered from one coastline in spring may differ measurably from a batch of the nominally same polymer collected elsewhere in autumn. For a regulatory agency, such variability is a serious problem, because a drug must deliver the same molecule, with the same quality attributes, every single time.

Solving that problem requires the kind of systematic thinking that the review tries to encourage. The authors argue that marine carbohydrates have too often been studied in terms of individual biological activities, with each research group reporting a single effect in isolation, while clinical development demands an integrated understanding of how structure, production, quality control and mechanism of action fit together. A candidate cannot advance if researchers cannot define its composition precisely, manufacture it consistently and explain how it works at the molecular level. The review therefore treats approved drugs and clinical candidates not just as success stories, but as case studies in how these elements can be aligned.

The priorities for future development that the authors identify are correspondingly practical. They call for reliable production methods based on cultivation, fermentation or enzymatic processing, which would decouple drug supply from wild harvesting and reduce batch-to-batch variation. They emphasize the need for improved quality control that combines structural characterization with activity-based assays, so that manufacturers can verify not only what a batch contains but what it does. They also stress the importance of validating molecular targets and mechanisms of action, and of conducting more rigorous pharmacokinetic and safety studies, areas in which complex carbohydrates have historically lagged behind small-molecule drugs because of their size, heterogeneity and analytical difficulty.

Achieving these goals, the review concludes, will require collaboration across disciplines that do not always work together. Senior and co-corresponding author Guangli Yu of the Ocean University of China notes that progress will depend on close cooperation among researchers in glycoscience, analytical chemistry, synthetic biology, materials science and clinical research. Co-corresponding author Chao Cai, also of the Ocean University of China, shares responsibility for the work, which was conducted within the Key Laboratory of Marine Drugs under the Ministry of Education and the Shandong Key Laboratory of Glycoscience and Glycotherapeutics. The interdisciplinary framing is deliberate: no single field currently possesses all the tools needed to characterize, manufacture and clinically validate a heterogeneous natural polymer.

The significance of the review lies less in any single discovery than in its synthesis. By following a clinical timeline that stretches from a 1969 leukemia drug to today’s trials in virology, oncology, metabolic disease and neurology, it demonstrates that marine carbohydrate therapeutics are not a speculative frontier but an evolving branch of pharmacology with a documented track record. The structural uniqueness of ocean-derived sugars, once a curiosity, is now understood as a design resource, and the field’s remaining challenges are the familiar ones of manufacturing, characterization and clinical evidence. If the collaborative agenda the authors describe takes hold, the next chapters of this timeline may be written not by chance discoveries in tide pools, but by engineered production systems capable of delivering the ocean’s chemistry with pharmaceutical precision.

Subject of Research: Marine carbohydrate-based drug development and clinical translation

Article Title: Marine carbohydrate therapeutics: from structural diversity to clinical translation

Article References: Marine carbohydrate therapeutics: from structural diversity to clinical translation. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: marine carbohydrates, polysaccharides, fucoidan, alginate, carrageenan, drug development, clinical trials, glycoscience, sulfation, antiviral, anticoagulant, Ocean University of China