Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor.

The coronavirus main protease, Mpro, is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential Mpro inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor.

Chemistry in the Circumstellar Medium: Unveiling the Dust Formation Zone

The growth of dust grains in the inner regions of late-type stars is shrouded in mystery due to the difficulty of understanding the growth of heterogeneous particles from simple atoms and molecules and the lack of observational data. This article reviews the molecular processes important in circumstellar envelopes and discusses how ALMA might be used to probe the dust formation zone either directly or indirectly.

Immunocolloidal Targeting of the Endocytotic Siglec-7 Receptor Using Peripheral Attachment of Siglec-7 Antibodies to Poly(Lactide-co-Glycolide) Nanoparticles

Purpose: To prepare a nanoparticulate formulation expressing variable peripheral carboxyl density using non-endcapped and endcapped poly(lactide-co-glycolide), conjugated to antibodies recognising the siglec-7 receptor, which is expressed on most acute myeloid leukaemias. The aim is to exploit this receptor as a therapeutic target by constructing an internalising drug-loaded nanoparticle able to
translocate into cytoplasm by siglec receptor-mediated internalisation.

Materials and Methods: Antibodies to the siglec-7 (CD33-like) receptor were conjugated to dye-loaded nanoparticles using carbodiimide chemistry, giving 32.6 mg protein per mg of nanoparticles using 100% of the non-endcapped PLGA. Binding studies using cognate antigen were used to verify preservation of antibody function following conjugation.

Results: Mouse embryonic fibroblasts expressing recombinant siglec-7 receptor and exposed to NileRed-loaded nanoparticles conjugated to antibody accumulated intracellular fluorescence, which was not observed if either antibody or siglec-7 receptor was absent. Confocal microscopy revealed internalised perinuclear cytoplasmic staining, with an Acridine Orange-based analysis showing red staining in localised foci, indicating localisation within acidic endocytic compartments.

Conclusions: Results show antibody-NP constructs are internalised via siglec-7 receptor-mediated internalisation. If loaded with a therapeutic agent, antibody-NP constructs can cross into cytoplasmic
space and delivery drugs intracellularly to cells expressing CD33-like receptors, such as natural killer cells and monocytes.

The journey to concordance for patients with hypertension: a qualitative study in primary care

Objective: We aimed to explore, using qualitative methods, the perspectives of patients with hypertension on issues relating to concordance in prescribing.

Method: This study took place in NHS general practices in Northern Ireland. A purposeful sample of patients who had been prescribed anti-hypertensive medication for at least one year were invited to participate in focus groups or semi-structured interviews; data were analysed using constant comparison.

Main outcome measures: The perspectives of patients with hypertension on issues relating to concordance in prescribing.

Results: Twenty-five individuals participated in five focus groups; two participated in semi-structured interviews. Participants felt they could make valuable contributions to consultations regarding their management. They were prepared to negotiate with GPs regarding their medication, but most deferred to their doctor’s advice, perceiving doctors’ attitudes and time constraints as barriers to their greater involvement in concordant decision-making. They had concerns about taking anti-hypertensive drugs, were aware of lifestyle influences on hypertension and reported using personal strategies to facilitate adherence and reduce the need to take medication.

Conclusions: Participants indicated a willingness to be?involved in concordance in prescribing anti- hypertensive medication but needed health professionals to address their concerns and confusion about the nature of hypertension. These findings suggest that there is a need for doctors and other healthcare professionals with responsibility for prescribing to develop skills specifically to explore the beliefs and views underlying an individual’s medication use. Such skills may need to be developed through specific training programmes at both undergraduate and postgraduate level.