Measles virus (MeV) is a paramyxovirus that infects humans, principally children. Despite the existence of an effective and safe vaccine, the number of cases of measles has increased due to lack of vaccination coverage. The World Health Organization (WHO) reports that the number of cases worldwide multiplied fourfold between January and March 2019, to 112,000. Today, there is no treatment available for MeV. In recent years, it has been demonstrated that natural extracts (herbal or algal) with antiviral activity can also work as reducing agents that, in combination with nanotechnology, offer an innovative option to counteract viral infections. Here, we synthetized and evaluated the antiviral activity of gold nanoparticles using garlic extract (Allium sativa) as a reducing agent (AuNPs-As). These nanoparticles actively inhibited MeV replication in Vero cells at a 50% effective concentration (EC₅₀) of 8.829 µg/mL, and the selectivity index (SI) obtained was 16.05. AuNPs-As likely inhibit viral infection by blocking viral particles directly, showing a potent virucidal effect. Gold nanoparticles may be useful as a promising strategy for treating and controlling the infection of MeV and other related enveloped viruses.

Sulfated polysaccharides (SPs) extracted from five seaweed samples collected or cultivated in Mexico (Macrocystis pyrifera,Eisenia arborea,Pelvetia compressa,Ulva intestinalis, andSolieria filiformis) were tested in this study in order to evaluate their effect on measles virusin vitro. All polysaccharides showed antiviral activity (as measured by the reduction of syncytia formation) and low cytotoxicity (MTT assay) at inhibitory concentrations. SPs fromEisenia arboreaandSolieria filiformisshowed the highest antiviral activities (confirmed by qPCR) and were selected to determine their combined effect. Their synergistic effect was observed at low concentrations (0.0274 μg/mL and 0.011 μg/mL ofE. arboreaandS. filiformisSPs, resp.), which exhibited by far a higher inhibitory effect (96% syncytia reduction) in comparison to the individual SP effects (50% inhibition with 0.275 μg/mL and 0.985 μg/mL ofE. arboreaandS. filiformis, resp.). Time of addition experiments and viral penetration assays suggest that best activities of these SPs occur at different stages of infection. The synergistic effect would allow reducing the treatment dose and toxicity and minimizing or delaying the induction of antiviral resistance; sulfated polysaccharides of the tested seaweed species thus appear as promising candidates for the development of natural antiviral agents.

Although preventable by vaccination, Measles still causes thousands of deaths among young children worldwide. The discovery of new antivirals is a good approach to control new outbreaks that cause such death. In this study, we tested the antiviral activity against Measles virus (MeV) of Polyphenol-rich extracts (PPs) coming from five seaweeds collected and cultivated in Mexico. An MTT assay was performed to determine cytotoxicity effect, and antiviral activity was measured by syncytia reduction assay and confirmed by qPCR. PPs from Ecklonia arborea (formerly Eisenia arborea, Phaeophyceae) and Solieria filiformis (Rhodophyta) showed the highest Selectivity Index (SI), >3750 and >576.9 respectively. Both PPs extracts were selected to the subsequent experiments owing to their high efficacy and low cytotoxicity compared with ribavirin (SI of 11.57). The combinational effect of PPs with sulphated polysaccharides (SPs) and ribavirin were calculated by using Compusyn software. Synergistic activity was observed by combining both PPs with low concentrations of Solieria filiformis SPs (0.01 µg/mL). The antiviral activity of the best combinations was confirmed by qPCR. Virucidal assay, time of addition, and viral penetration evaluations suggested that PPs act mainly by inactivating the viral particle. To our knowledge, this is the first report of the virucidal effect of Polyphenol-rich extracts of seaweeds.

Oxidative stress has been linked to neurodegenerative diseases such as Huntington’s, Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis diseases. Larrea tridentata (LT) also known as Creosote Bush is an evergreen shrub found in the Chihuahuan desert which has been used medicinally by Native American tribes in southwestern North America and the Amerindians of South America. However, studies of the antioxidant capacity of the crude extract of LT towards the discovery of novel molecular therapies bearing antioxidants and drug-like properties are lacking. In this study, we assessed the antioxidant properties of Larrea tridentata, collected specifically from the Chihuahuan desert in the region of El Paso del Norte, TX, USA. LT phytochemicals were obtained from three different extracts (ethanol; ethanol: water (60:40) and water). Then the extracts were evaluated in eight different assays (DPPH, ABTS, superoxide; FRAP activity, nitric oxide, phenolic content, UV visible absorption and cytotoxicity in non-cancerous HS27 cells). The three extracts were not affecting the HS27 cells at concentrations up to 120 µg/mL. Among the three extracts, we found that the mixture of ethanol: water (60:40) LT extract has the most efficient antioxidant properties (IC₅₀ (DPPH at 30 min) = 111.7 ± 3.8 μg/mL; IC₅₀ (ABTS) = 8.49 ± 2.28 μg/mL; IC₅₀ (superoxide) = 0.43 ± 0.17 μg/mL; IC₅₀ (NO) = 230.4 ± 130.4 μg/mL; and the highest phenolic content was estimated to 212.46 ± 7.05 mg GAE/L). In addition, there was a strong correlation between phenolic content and the free-radical scavenging activity assays. HPLC-MS study identified nine compounds from the LT-ethanol: water extract including Justicidin B and Beta peltain have been previously reported as secondary metabolites of Larrea tridentata.

In this study, we identified a novel pyrazole-based derivative (P3C) that displayed potent cytotoxicity against 27 human cancer cell lines derived from different tissue origins with 50% cytotoxic concentrations (CC₅₀) in the low micromolar and nanomolar range, particularly in two triple-negative breast cancer (TNBC) cell lines (from 0.25 to 0.49 µM). In vitro assays revealed that P3C induces reactive oxygen species (ROS) accumulation leading to mitochondrial depolarization and caspase-3/7 and -8 activation, suggesting the participation of both the intrinsic and extrinsic apoptotic pathways. P3C caused microtubule disruption, phosphatidylserine externalization, PARP cleavage, DNA fragmentation, and cell cycle arrest on TNBC cells. In addition, P3C triggered dephosphorylation of CREB, p38, ERK, STAT3, and Fyn, and hyperphosphorylation of JNK and NF-kB in TNBC cells, indicating the inactivation of both p38MAPK/STAT3 and ERK1/2/CREB signaling pathways. In support of our in vitro assays, transcriptome analyses of two distinct TNBC cell lines (MDA-MB-231 and MDA-MB-468 cells) treated with P3C revealed 28 genes similarly affected by the treatment implicated in apoptosis, oxidative stress, protein kinase modulation, and microtubule stability.