Lead identification and structure-activity relationships of heteroarylpyrazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists

A knowledge-based library of aryl 2,3-dichlorophenylsulfonamides was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. X-ray diffraction studies were used to identify the pyrazole ring as a moiety that could bring about intramolecular hydrogen bonding with the sulfonamide NH and provide a clip or orthogonal conformation that was believed to be the preferred active conformation. Replacement of the core phenyl ring with a pyridine, and replacement of the 2,3-dichlorobenzenesulfonamide with 5- chlorothiophenesulfonamide provided compound 33 which has excellent physicochemical properties and represents a good starting point for a lead optimisation programme. Electronic structure calculations indicated that the preference for the clip or orthogonal conformation found in the small molecule crystal structures of 7 and 14 was in agreement with the order of potency in the biological assay

Participatory Videos: A New Media for Promoting Organic Farming in Northern Bangladesh

Significance of agricultural extension to eliminate poverty, vulnerability, hunger and pollution is well-established in the perspective of developing countries. However, extension services in Bangladesh missed the opportunity to reduce poverty and pollution in a cost-effective way. This is due to lack of innovative ways to support farmer-to-farmer learning process. This paper presents the thoughts, empirical evidences and vision about approaches of video-mediated learning to enhance household food security and reducing pollution caused by agro-chemicals used in the field of agriculture. Following a model of participatory video (PV) supported women farmers’ capacity building process for preparation and use of botanical pesticide and vermin-compost in organic vegetables production. Findings of the study showed that PV has unexploited potentials to promote farmers’ innovation and adoption of organic farming by the farmers in the study area

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant