Medicinal Immunoglobulin G Products (2020) Show High Infectivity Neutralizing Activity Against Seasonal Influenza Virus Strains Selected for Future Vaccines (2020-2022).

Immunoglobulin (Ig)G medicinal products manufactured in 2020 were tested for infectivity neutralization and hemagglutination inhibition against World Health Organization-selected influenza strains included in worldwide vaccines 2020-2022. The IgG batches (from US plasma) showed potent activity. Intravenous immunoglobulin could potentially add to therapies for serious influenza cases in immunocompromised patients. Further study is warranted.

Application of a phenotypic drug discovery strategy to identify biological and chemical starting points for inhibition of TSLP production in lung epithelial cells.

Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation. To this end, a phenotypic screen was performed using poly I:C / IL-4 stimulated NHBE cells interrogated with a 44,974 compound library. As a result, 85 hits which downregulated TSLP protein and mRNA levels were identified and a representative subset of 7 hits was selected for further characterization. These molecules inhibited the activity of several members of the MAPK, PI3K and tyrosine kinase families and some of them have been reported as modulators of cellular phenotypic endpoints like cell-cell contacts, microtubule polymerization and caspase activation. Characterization of the biological profile of the hits suggested that mTOR could be a key activity involved in the regulation of TSLP production in NHBE cells. Among other targeted kinases, inhibition of p38 MAPK and JAK kinases showed different degrees of correlation with TSLP downregulation, while Syk kinase did not seem to be related. Overall, inhibition of TSLP production by the selected hits, rather than resulting from inhibition of single isolated targets, appeared to be due to a combination of activities with different levels of relevance. Finally, a hit expansion exercise yielded additional active compounds that could be amenable to further optimization, providing an opportunity to dissociate TSLP inhibition from other non-desired activities. This study illustrates the potential of phenotypic drug discovery to complement target based approaches by providing new chemistry and biology leads.

Discovery of a novel class of zwitterionic, potent, selective and orally active S1P1 direct agonists.

Amido-1,3,4-thiadiazoles have been identified as a novel structural class of potent and selective sphingosine-1-phosphate receptor subtype 1 agonists. Starting from a micromolar HTS hit with the help of an in-house homology model, robust structural-activity relationships were developed to yield compounds with good selectivity and excellent in vivo efficacy in rat models.

Disseminated cytomegalovirus disease as a cause of prolonged fever in a bullous pemphigoid patient under systemic steroid therapy.

We present the first reported case of disseminated cytomegalovirus (CMV) in association with prednisone therapy in bullous pemphigoid (BP). A 66-year-old black male patient was admitted to our hospital presenting cutaneous pruritic lesions represented by tense blisters, with serous content on the arms, abdomen and legs. Laboratory findings confirmed the diagnosis of BP. After two weeks of prednisone therapy, the patient developed prolonged fever, which was caused by CMV disseminated disease, with prompt clinical recovery after ganciclovir administration.