Cooperation in a fluid swarm of fuel-free micro-swimmers

While motile bacteria display rich dynamics in dense colonies, the phoretic nature of artificial micro-swimmers restricts their activity when crowded. Here we introduce a new class of synthetic micro-swimmers that are driven solely by light. By coupling a light absorbing particle to a fluid droplet we produce a colloidal chimera that transforms optical power into propulsive thermo-capillary action. The swimmers’ internal drive allows them to operate for a long duration (days) and remain active when crowded, forming a high density fluid phase. We find that above a critical concentration, swimmers form a long lived crowded state that displays internal dynamics. When passive particles are introduced, the dense swimmer phase can re-arrange to spontaneously corral the passive particles. We derive a geometrical, depletion-like condition for corralling by identifying the role the passive particles play in controlling the effective concentration of the micro-swimmers.

A Review of the Current Landscape of SARS-CoV-2 Main Protease Inhibitors: Have We Hit the Bullseye Yet?

In this review, we collected 1765 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) M-pro inhibitors from the bibliography and other sources, such as the COVID Moonshot project and the ChEMBL database. This set of inhibitors includes only those compounds whose inhibitory capacity, mainly expressed as the half-maximal inhibitory concentration (IC50) value, against M-pro from SARS-CoV-2 has been determined. Several covalent warheads are used to treat covalent and non-covalent inhibitors separately. Chemical space, the variation of the IC50 inhibitory activity when measured by different methods or laboratories, and the influence of 1,4-dithiothreitol (DTT) are discussed. When available, we have collected the values of inhibition of viral replication measured with a cellular antiviral assay and expressed as half maximal effective concentration (EC50) values, and their possible relationship to inhibitory potency against M-pro is analyzed. Finally, the most potent covalent and non-covalent inhibitors that simultaneously inhibit the SARS-CoV-2 M-pro and the virus replication in vitro are discussed.

Impact of L-carnitine supplementation on the in vitro developmental competence and cryotolerance of buffalo embryos

Background and Aim: Despite many trials, buffalo embryos have poor cryosurvivability because of their high lipid content. L-carnitine was found to be a lipid-reducing agent when added to oocyte and embryo culture media. The study aimed to determine the most effective concentration of L-carnitine to improve the oocyte developmental competence and cryotolerance of buffalo embryos. Materials and Methods: In vitro maturation and embryo culture media were supplemented with four concentrations of L-carnitine: 0 (control), 0.25, 0.5, and 1 mM. Good-quality embryos on 7 days were vitrified using mixtures of dimethyl sulfoxide and ethylene glycol at two concentrations (3.5 and 7 M). Results: The result showed that the cleavage and morula rates were significantly (p<0.05) higher in the 0.5 mM group. Blastocyst rates were significantly (p<0.05) higher at both 0.5 and 1 mM. The rates of viable embryos directly after thawing were significantly (p<0.05) increased in the 0.5 mM group. No significant difference was found in embryos cultured for 24 h after warming among all the groups. Conclusion: The addition of L-carnitine at a concentration of 0.5 mM to the culture media improves the oocyte developmental competence and cryotolerance of buffalo embryos directly after warming but not after 24 h of culture. Nevertheless, further studies must identify how L-carnitine exerts its beneficial micromechanisms.

Activity of terpenes derived from essential oils against Sarcoptes scabiei eggs

Background The limited ovicidal activity of currently available acaricides is a significant obstacle to efficacious scabies treatment. Several essential oils or their respective components have proved to be active against the eggs of arthropods, mainly lice and ticks. Information on the activity of these oils and/or components against the eggs of mites remains very limited. The aim of this study was to assess the activity of six terpenes (carvacrol, eugenol, geraniol, citral, terpinen-4-ol and linalool) commonly found in essential oils against the eggs of Sarcoptes scabiei. Methods Sarcoptes eggs were exposed to paraffin oil containing 1, 2.5, or 5% of each terpene tested. After a 12-h exposure period, the eggs were washed and placed in paraffin oil for hatching. Embryonic development following treatment was assessed every day to determine the stage of developmental arrest. Results The median effective concentration to obtain 50% egg mortality (EC50) was 0.5, 0.9, 2.0, 4.8, 5.1 and 9.8% for carvacrol, eugenol, geraniol, citral, terpinen-4-ol and linalool, respectively. The microscopic images of eggs after each treatment indicated that these six terpenes may act by penetrating through the aeropyles on the egg surface. Conclusions In conclusion, carvacrol, eugenol and geraniol possess significant ovicidal activities, which should be considered as promising ovicidal agents for the treatment of scabies. Graphical Abstract

Pyrazoline derivatives as promising novel antischistosomal agents

Praziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15–31) and three pyrazoles (32–34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC50) below 30 μM. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC50 < 10 µM. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure–activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies’ filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.

Ecotoxic Effects of the Vehicle Solvent Dimethyl Sulfoxide on Aquatic Model Organisms

Dimethyl sulfoxide (DMSO) is widely used as a vehicle solvent in ecotoxicity bioassays. However, despite its frequent use, itcould be toxic for organisms at some concentrations. Hence, the aim of this study was to investigate the effectsof DMSO on the population growth rate of the microalgaeRaphidocelis subcapitata, the mobility of the microcrustacean Daphnia magna,and the reproduction of the rotiferBrachionus calyciflorus. DMSO was applied to the organisms in concentrations ranging from 0.031–4%. For R. subcapitata significant effects in growth inhibitionafter 72 h of exposure was 0.125% DMSO,being the lowest observed effectconcentration (LOEC). The 50% effective concentration (EC50) was2.138 ± 0.372%. In D. magna,significant differences in the mobility after 24 h or 48 h of exposure was 1% DMSO being 1.712± 0.207% and 1.167± 0.220%DMSO the EC50 observed for 24 h and 48 h exposure, respectively. For B. calyciflorus,it was not possible to validate the tests performed, as there were insufficient animals alive in the control conditions at the end of the exposure period. Therefore, we recommended avoiding DMSO as a vehicle in assays using B. calyciflorus,and to use final DMSO concentrationsin experimental solution not exceeding 0.125% forR. subcapitata and 0.5% for D. magna.

Synthesis and Evaluation of Trypanocidal Activity of Chromane-Type Compounds and Acetophenones

American trypanosomiasis (Chagas disease) caused by the Trypanosoma cruzi parasite, is a severe health problem in different regions of Latin America and is currently reported to be spreading to Europe, North America, Japan, and Australia, due to the migration of populations from South and Central America. At present, there is no vaccine available and chemotherapeutic options are reduced to nifurtimox and benznidazole. Therefore, the discovery of new molecules is urgently needed to initiate the drug development process. Some acetophenones and chalcones, as well as chromane-type substances, such as chromones and flavones, are natural products that have been studied as trypanocides, but the relationships between structure and activity are not yet fully understood. In this work, 26 compounds were synthesized to determine the effect of hydroxyl and isoprenyl substituents on trypanocide activity. One of the compounds showed interesting activity against a resistant strain of T. cruzi, with a half effective concentration of 18.3 µM ± 1.1 and an index of selectivity > 10.9.

Assessing the effectiveness of oxathiapiprolin towards Phytophthora agathidicida, the causal agent of kauri dieback disease

Phytophthora species cause disease and devastation of plants in ecological and horticultural settings worldwide. A recently identified species, P. agathidicida, infects and ultimately kills the treasured kauri trees (Agathis australis) that are endemic to New Zealand. Currently there are few options for managing kauri dieback disease. In this study, we sought to assess the toxicity of the oomycide oxathiapiprolin against several life cycle stages of two geographically distinct P. agathidicida isolates. The effective concentration to inhibit 50% of mycelial growth (EC50) was determined to be approximately 0.1 ng/ml, indicating that P. agathidicida mycelia are more sensitive to oxathiapiprolin than those from most other Phytophthora species that have been studied. Oxathiapiprolin was also highly effective at inhibiting the germination of zoospores (EC50 = 2–9 ng/ml for the two isolates) and oospores (complete inhibition at 100 ng/ml). In addition, oxathiapiprolin delayed the onset of detached kauri leaf infection in a dose-dependent manner. Collectively, the results presented here highlight the significant potential of oxathiapiprolin as a tool to aid in the control of kauri dieback disease.

Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants

We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Stenoparib is an inhibitor of mammalian poly (ADP-ribose) polymerases (PARPs). Here we show that stenoparib effectively inhibits additional SARS-CoV-2 variants, including an additional wild-type strain (Germany/BavPat1/2020), and the variants alpha (B.1.1.7), beta (B.1.351) and gamma (P.1) in vitro, with 50% effective concentration (EC50) estimates of 4.1 μM, 8.5 μM, 24.2 μM and 13.6 μM, respectively. A second study focusing on a combination of 10 μM stenoparib and 0.5 µM remdesivir resulted in over 90% inhibition of the alpha (B.1.1.7) variant, which is substantially greater than what was achieved with stenoparib or remdesivir alone at these concentrations.