Histones are classical DNA-binding proteins, rich in cationic amino acids, and recently also reported as effective antimicrobial agents against a range of Gram-negative and Gram-positive pathogens. While histones with antimicrobial functions have been identified in various marine organisms, little is known regarding the identification and characterisation of innate antimicrobial proteins and peptides, including histones, from macroalgae species. This study aimed to develop an isolation and purification protocol for histones by combining in-silico analyses with wet-laboratory techniques to identify and isolate core histones from the red macroalga Chondrus crispus. The antimicrobial properties of the purified core histone were examined against a variety of pathogenic bacteria using both minimum inhibitory concentration (MIC) and disk diffusion assays. The purification of the core histone fraction was assessed using SDS-PAGE analysis. The findings indicated that the core histone extracted from C. crispus displayed antimicrobial properties against a range of Gram-positive and Gram-negative bacteria, including Escherichia coli, Staphylococcus aureus, and the marine pathogens Vibrio anguillarum and Yersinia ruckeri. Furthermore, the purified core histone was digested by trypsin into peptides. The resulting peptides exhibited enhanced bacterial inhibition against both E. coli and S. aureus. These results indicate, for the first time, that C. crispus histone proteins and peptides possess antimicrobial activity. In addition to its antimicrobial properties, the purified core histone showed minimal cytotoxic effects when tested in mammalian cells. As a result, the core histone obtained from C. crispus shows potential as a novel antimicrobial candidate, supporting further evaluation across additional mammalian cell types.

Marine ecosystems are a vast, underexplored reservoir of bioactive compounds with unique structural diversity and potent biological activities. Enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continue to pose significant global health threats, exacerbated by emerging variants, limited therapeutic options beyond vaccines, and challenges such as drug resistance and immune dysregulation. Compounds derived from marine organisms, including lectins (e.g., griffithsin from red algae Griffithsia sp.), sulfated polysaccharides (e.g., iota-carrageenan from red algae Chondrus crispus), polyphenols (e.g., dieckol from brown algae Ecklonia cava), and depsipeptides (e.g., plitidepsin from tunicates), have shown promising antiviral effects in preclinical studies. These molecules primarily act by inhibiting viral entry (via the spike glycoprotein or glycan binding), replication (targeting proteases such as the main protease [Mpro] and the RNA-dependent RNA polymerase [RdRp]), or by modulating host immune responses (e.g., reducing cytokine storms or oxidative stress). In vitro, in vivo, and in silico evidence highlights their potential against SARS-CoV-2 and related enveloped viruses (e.g., HIV, HSV, influenza, HCMV), which share mechanistic similarities, including envelope-mediated fusion and RNA-based replication. This narrative review provides a cohesive overview of selected marine-derived bioactive compounds with reported activity against SARS-CoV-2 and other enveloped viruses. It examines their sources, structural features, mechanisms of action, key activity metrics (e.g., IC50/EC50 values), and translational prospects, and addresses challenges such as scalability, preclinical-to-clinical gaps, and sustainability aligned with the European Blue Economy. By integrating recent findings, this review aims to highlight promising leads and guide future research toward innovative, broad-spectrum antiviral therapies.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of red algae-derived ingredients. Sixty red algae-derived ingredients were found in the International Cosmetic Ingredient Dictionary (Dictionary); however, several of these ingredients may be equivalent according to accepted scientific names. These ingredients are mostly reported to function in cosmetics as skin-conditioning agents. Impurities, particularly arsenic, heavy metals, and pesticides, may be present in these ingredients; industry should continue to use good manufacturing practices to monitor and limit these possible impurities. The Panel considered the available data and concluded that 16 red algae-derived ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment. The Panel also concluded that the data are insufficient to make a determination of safety that the remaining 44 ingredients are safe under the intended conditions of use in cosmetic formulations.

Sea moss has gained popularity as a functional food, yet information on the microbial quality, physicochemical characteristics, and heavy metal concentrations of commercially available products remains limited. This study evaluated 66 sea moss products purchased from major online retailers in the United States, including 53 dried sea moss products and 13 sea moss gels. Water activity ranged from 0.33 to 0.76 (0.59 ± 0.11) in dried sea moss and from 0.74 to 1.00 (0.98 ± 0.07) in gels. Sea moss gels exhibited substantial variability in pH (2.71-7.05) and °Brix (0.80-46.10). Mean total plate counts were 4.30 and 3.92 log CFU/g in dried sea moss and gels, respectively, while mean yeast and mold counts were 3.23 and 3.60 log CFU/g. Presumptive Bacillus and Staphylococcus spp. were recovered from both product types, while presumptive Escherichia, Salmonella, Listeria, and Vibrio spp. were detected less frequently. Molecular characterization of selected isolates identified Bhargavaea, Exiguobacterium, Staphylococcus, Salmonella, Cronobacter, Bacillus, and Escherichia spp.; Listeria and Vibrio spp. were not identified among isolates yielding interpretable sequence results. Arsenic, cobalt, and mercury were detected in dried sea moss, whereas arsenic and cobalt were below the limits of detection in the gels and mercury was detected at trace concentrations. Substantial variability in microbial and physicochemical characteristics among commercial sea moss products highlights the need for additional research and evidence-based guidance to support appropriate processing, storage, and handling practices.

Cannabidiol (CBD) is a lipophilic phytocannabinoid of interest for dermocosmetic and topical applications, but its poor aqueous solubility and sensitivity to environmental conditions make its formulation challenging. This work aimed to develop avocado oil-in-water emulgels for CBD incorporation using a mixed emulsifying system based on Kolliphor EL and cricket protein and a commercial Aloe vera/Chondrus crispus gel as the structuring phase. First, different Kolliphor EL:cricket protein ratios were evaluated according to droplet size distribution. No significant differences in droplet size were found among formulations containing at least 67% Kolliphor EL (p > 0.05); therefore, 67K-33G was selected because it maximized the substitution of Kolliphor EL with cricket protein without significantly affecting droplet size. Progressive replacement of water by the commercial hydrocolloid gel markedly increased consistency and viscoelasticity, producing a transition from fluid emulsions to elastic emulgels between 50 AV and 75 AV. The 75 AV formulation showed low Turbiscan Stability Index values, a predominantly elastic response, and a more balanced structure than 100 AV. The selected emulgel showed a total analytical recovery of 96.2 ± 1.2% for CBD and retained 97.3 ± 0.7% of the initially recovered CBD after 30 days of storage at 4 °C protected from light. These results support the potential of Aloe vera/Chondrus crispus-based emulgels as semisolid carriers for lipophilic bioactive compounds.

Vanadium-dependent haloperoxidases are enzymes found in bacteria, fungi and red or brown macroalgae. They are used as a defense system for the latter by producing bromoform. The intermediate product, HOBr or HOCl, is also a microbicidal compound that can be exploited in many domains as medical tools or disinfectant sprays for example. We show that the mutation identified in Ohshiro's work, which alters substrate specificity toward chloride, is transferable to the homologous enzyme from Chondrus crispus. We then applied genetic and enzymatic engineering to design a chimera with glucose oxidase, thereby enhancing antimicrobial properties by providing a local source of H2O2. We used the SpyTag/SpyCatcher technology to form the chimera and obtained homogenous objects, indicating that one oligomeric form is favored. We demonstrated the release of HOBr and HOCl thanks to NADH that reacts spontaneously with it outside the active site of the enzyme. We also measured the steady-state kinetic parameters of the wild-type or modified enzymes. The formation of the chimera increased the specificity of ccVHPO1 inside the chimera, towards KBr or H2O2, compared to the enzyme alone with the SpyCatcher. Finally, we showed a significant increase in the microbicidal effect between a coupled enzymatic system with the glucose oxidase (the two enzymes are free in solution) compared to the chimera system, which is completely bactericidal at concentrations around 20 nM.

Therapy resistance is attributed to over 80% of cancer deaths per year, emphasizing the urgent need to overcome this challenge for improved patient outcomes. Despite its widespread use in colorectal cancer (CRC) treatment, resistance to 5-fluorouracil (5FU) remains poorly understood. As an antimetabolite, 5FU imposes substantial metabolic stress, forcing cells that survive treatment to rapidly adapt. We explored acute 5FU-driven changes in mitochondria, the organelle critical for coordinating metabolic stress responses. Here we demonstrate in a range of CRC models that 5FU treatment promotes mitochondrial biogenesis and increases mitochondrial function in surviving cells. Furthermore, we show that targeting mitochondrial metabolism, particularly by inhibiting Complex I, sensitizes CRC cells to 5FU, resulting in delayed tumour growth and prolonged survival in preclinical models. Additionally, analysis of patient data suggests that oxidative metabolism signatures may predict responses to 5FU-based chemotherapy. These findings shed light on mechanisms underlying 5FU resistance and propose a rational strategy for combination therapy in CRC, emphasizing the potential clinical benefit of targeting mitochondrial metabolism to overcome resistance and enhance patient outcomes.

Structural coloration, a physical phenomenon observed in many living organisms, may arise from the interference of light with highly organized surface nanostructures. In some seaweeds, these nanostructures consist of cuticular lamellae in the outer part of the extracellular matrix (ECM) of the epidermis. However, the chemical composition of seaweed cuticles is poorly understood and the molecular components of lamellae remain unidentified. Here, we use integrated genomic, transcriptomic, proteomic, and metabolomic approaches together with analytical profiling of carbohydrates to determine the composition of the multilayered cuticle in the red alga Chondrus crispus and assess its evolutionary conservation. The structural assembly reveals common features with the ECM of animals. The carbohydrate fraction includes a complex mixture of carrageenans and glycosaminoglycan-like compositions. A major von Willebrand factor A domain protein, Lamellae Cohesive Protein, plays a critical role in protein-protein interactions and binding to sulfated polysaccharides. We have further identified the major proteins of the algal cuticle, providing a framework for addressing the evolutionary origins of the cuticle and raising important questions regarding its role, particularly across the red algal life cycle marked by major structural differences in its ECM.

A quantitative NMR assay was utilized to identify methylglyoxal-scavenging natural products from Rhodophytes, Chondrus crispus and Gracilaria vermiculophylla. This revealed the activity of guanylurea-containing amino acid derivatives, gongrine and gigartinine. The molecules share structural features with the frontline blood glucose-lowering drug and plant natural product derivative, metformin, and scavenge methylglyoxal via the same mechanism, resulting in an imidazole-containing Advanced Glycation Endproduct or AGE. The protective effect of the molecules reported here was evaluated in a cell-based model for reactive aldehyde stress using methylglyoxal exposure to reduce cell viability. Gongrine, gigartinine, and metformin all preserve cell viability in HepG2 following methylglyoxal exposure. This is the first report of methylglyoxal scavenging and cell viability protection of these macroalgae-derived guanylurea-containing natural products, which can be found in high abundance in commonly consumed and industrially produced macroalgae species. The compounds presented here, along with their algal sources, offer a unique opportunity to produce guanylureas with therapeutic potential through sustainable production methods from easily cultivated algal sources.

Mycosporine-like amino acids (MAAs) are photoprotective compounds primarily produced by marine organisms, especially red algae. Chemically, MAAs and their precursors are low-molecular-weight natural products that absorb ultraviolet radiation in the range of 270-360 nm without generating free radicals. Owing to these properties, MAAs have attracted considerable interest for potential pharmaceutical and cosmetic applications as natural sunscreen agents. In this study, the first hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC) method, coupled with both diode array detector (DAD) and tandem mass spectrometry (MS/MS), was developed for the determination of 11 MAAs and 2 MAA precursors in various algal species. As column, a YMC-Triart Diol-HILIC (particle size: 1.9 µm) was used, and the separation of the MAAs realized in under 5 min. The validation of the method was carried out following International Council for Harmonisation (ICH) guidelines, demonstrating linearity, selectivity, precision, and accuracy. The analysis of extracts prepared from well-known species, such as Porphyra sp. and Chondrus crispus, confirmed practical applicability. Demonstrating feasibility of MS/MS-based quantification of co-eluting compounds, the method represents an appealing alternative that surpasses established procedures not only in terms of analysis time but also by providing a substantially increased informative value.

Sulfated polysaccharides, carrageenans (CRGs) derived from Chondrus armatus, were used as mucoadhesive matrices for incorporating the antiviral drug acyclovir (ACV). Through IR spectroscopy and quantum-chemical calculations, it was demonstrated that CRGs interact with ACV, forming complexes via intermolecular hydrogen bonding and coordination interactions, with an enthalpy of approximately 15-20 kcal/mol. The monomodal ζ-potential distribution observed in the CRG/ACV mixture confirmed the successful formation of this complex. The antiviral efficacy of the CRG/ACV complex was evaluated during the early stages of herpes simple virus (HSV-1) infection, focusing on its ability to inhibit the cytopathic effects of the virus on host cells. Notably, CRGs enhanced antiviral activity by allowing a reduction in the ACV dosage. Unlike ACV alone, the CRG complex exhibited a prophylactic effect, with therapeutic efficacy comparable to that of ACV. When incorporated into liposomes, the CRG/ACV complex displayed excellent mucoadhesive properties. This liposomal formulation demonstrated notable antiviral activity against infected cells with selective index (SI) 344 and a heightened prophylactic effect (SI 128) compared to the complex alone. Overall, these new antiviral compounds show promise in selectively inhibiting viral adsorption and replication processes without adversely affecting the host organism.

A novel cold-adapted κ-carrageenase (Car2891) was identified from the marine bacterium Cellulophaga sp. P-1 isolated from Chondrus. The enzyme was recombinantly expressed in E. coli BL21(DE3) and biochemically characterized. Car2891 exhibited optimal activity at 30 °C and pH 8.0, maintaining high stability and catalytic performance from 0 °C to 30 °C under neutral-weakly alkaline conditions. Its activity was enhanced by Na[+], Mg[2+], and Mn[2+] but strongly inhibited by Hg[2+], Cu[2+], Ni[2+], and EDTA. Kinetic analysis revealed a Km value of 6.1 mg mL[-1] and a Vmax value of 31.65 mg mL[-1] min[-1] for κ-carrageenan. Hydrolysis pattern analysis revealed an endo-acting cleavage mechanism, initially yielding hexa- and tetrasaccharides, with disaccharides and tetrasaccharides as the final major products. These properties demonstrate Car2891's potential as an efficient and controllable biocatalyst for the environmentally friendly processing of κ-carrageenan and the scalable production of functional oligosaccharides.

Seaweed are primary producers and potential vectors of microplastics (MPs) contamination, yet robust extraction methods that digest complex algal matrices while preserving polymer integrity remain limited. A sequential enzymatic-oxidative digestion was optimized for three seaweeds (Fucus vesiculosus, Chondrus crispus and Ulva lactuca). The optimized process involved the initial addition of cellulase (1% w/v, 24 h, 50 °C) followed by H₂O₂ (30% v/v, 48-72 h, 65 °C). Across nine 0.5 g dry-weight sub-replicates (3 per seaweed), 30 MPs were found (6.7 MPs/g⁻¹). The integrity of polymers was assessed for 12 MPs polymers, with acceptable performance being defined as ≥ 90% recovery and spectroscopic (through FTIR analysis) identifiability. Eight polymers met this threshold (90-101%). Four polymers were adversely affected with the long 72 H₂O₂ incubation, namely: cellulose-acetate (53% recovery), polyamide (61%), acrylic (3%) and rayon (2%). Although polymers remained identifiable, sequential digestion produced mass loss and visible changes (e.g. polyamide opacity, cellulose-acetate brittleness), which may increase fragmentation and miss-identification. Therefore, the protocol is suitable for most common MPs, but not for rayon and acrylic, and should be applied cautiously where cellulose-acetate or polyamide are expected.