Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro

Background: Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 M compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC), cytotoxicity (CC) and the in vitro therapeutic index in live virus and pseudotype assay formats. Results: While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. Conclusion: All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies

All-aqueous continuous-flow RAFT dispersion polymerisation for efficient preparation of diblock copolymer spheres, worms and vesicles

We report the scalable, all-aqueous synthesis of polyIJdimethylacrylamide)–polyIJdiacetone acrylamide) (PDMAm–PDAAm) diblock copolymer spheres, worms and vesicles by reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerisation in a low-cost continuous-flow (CF) reactor. A transient state kinetic profiling method using a 5 mL reactor coil indicated a considerably faster rate than the equivalent batch reaction. Higher throughput was subsequently demonstrated by employing a 20 mL coil reactor for the synthesis of a 135 g, 30% w/w batch of PDMAm113 macromolecular chain transfer agent (macro-CTA) at 98% conversion. This was used without further purification to polymerise DAAm in a CF reactor. During this polymerisation, the chains underwent polymerisation-induced self-assembly (PISA) producing block copolymer spheres. This reaction also proceeded faster than in batch, and the high resolution kinetics enabled clear observation of the rate enhancement which is characteristic of PISA systems. GPC studies indicated the formation of a copolymer with low molar mass dispersity and complete blocking efficiency, despite the high conversion achieved during the precursor macro-CTA synthesis. It was subsequently demonstrated that the PDMAm113 macro-CTA could be used to prepare PDMAm113–PDAAmx block copolymer spheres (where x = 50, 100 and 200) with systematically increasing particle diameters. Finally, by reducing the PDMAm macro-CTA DP to 50 and increasing total solids to 20% w/w, it was possible to prepare worms and vesicles in the tubular reactor by tailoring the residence time to achieve specific degrees of polymerisation of the PDAAm block

Asymmetric copolymers: synthesis, properties, and applications of gradient and other partially segregated copolymers

This is an accepted manuscript of an article published by Wiley in Macromolecular Rapid Communications, available online: https://doi.org/10.1002/marc.201800357 The accepted version of the publication may differ from the final published version.Asymmetric copolymers are a class of materials with intriguing properties. They can be defined by a distribution of monomers within the polymer chain that is neither strictly segregated, as in the case of block copolymers, nor evenly distributed throughout each chain, as in the case of statistical copolymers. This definition includes gradient copolymers as well as block copolymers that contain segments of statistical copolymer. In this review, different methods to synthesize asymmetric copolymers are first discussed. The properties of asymmetric copolymers are investigated in comparison to those of block and random counterparts of similar composition. Finally, some examples of applications of asymmetric copolymers, both academic and industrial, are demonstrated. The aim of this review is to provide a perspective on the design and synthesis of asymmetric copolymers with useful applications.This research was financially supported by the ASYMCOPO Project, an international collaborative research project of the Deutsche Forschungsgemeinschaft (DFG, Germany) and the Agence Nationale de la Recherche (ANR, France); DFG project: GU 1685/1-1 (J. Z., C. G. S. and U. S. S.) and ANR project ANR-15-CE08-0039 (S. H.). C. G. S. and U. S. S. thank the Center for Excellence “PolyTarget” (SFB 1278, project Z01) of the Deutsche Forschungsgemeinschaft (DFG, Germany) for financial support. B. F. M. acknowledges the financial support from Consejo Nacional de Ciencia y Tecnologia (CONACyT, Mexico) to pursue her PhD.Published versio

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