Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PL and M proteases, and nsp14 guanine N7-methyltransferase.

Proteases encoded by SARS-CoV-2 constitute a promising target for new therapies against COVID-19. SARS-CoV-2 main protease (M, 3CL) and papain-like protease (PL) are responsible for viral polyprotein cleavage-a process crucial for viral survival and replication. Recently it was shown that 2-phenylbenzisoselenazol-3(2H)-one (ebselen), an organoselenium anti-inflammatory small-molecule drug, is a potent, covalent inhibitor of both the proteases and its potency was evaluated in enzymatic and antiviral assays.

Assessment of the Function of Respiratory Muscles in Patients after COVID-19 Infection and Respiratory Rehabilitation.

Objectives: The MIP (maximum inspiratory pressure) and MEP (maximum expiratory pressure) are sensitive indicators of respiratory muscle function. The aim of the study was to assess the function of respiratory muscles in patients after COVID-19 infection, before and after hospitalisation at the Pulmonary Rehabilitation Ward.

Materials And Methods: The study was conducted on a group of 19 people with laboratory-confirmed COVID-19 infection, who, in the period from 1 February to 31 May 2021, were hospitalised at the Independent Public Pulmonary Hospital and underwent respiratory rehabilitation in hospital conditions.

Optimized Ebselen-Based Inhibitors of Bacterial Ureases with Nontypical Mode of Action.

Screening of 25 analogs of Ebselen, diversified at the N-aromatic residue, led to the identification of the most potent inhibitors of urease reported to date. The presence of a dihalogenated phenyl ring caused exceptional activity of these 1,2-benzisoselenazol-3(2)-ones, with value in a low picomolar range (<20 pM). The affinity was attributed to the increased π-π and π-cation interactions of the dihalogenated phenyl ring with αHis323 and αArg339 during the initial step of binding.

Discovery of 5-{2-[5-Chloro-2-(5-ethoxyquinoline-8-sulfonamido)phenyl]ethynyl}-4-methoxypyridine-2-carboxylic Acid, a Highly Selective in Vivo Useable Chemical Probe to Dissect MCT4 Biology.

Due to increased lactate production during glucose metabolism, tumor cells heavily rely on efficient lactate transport to avoid intracellular lactate accumulation and acidification. Monocarboxylate transporter 4 (MCT4/SLC16A3) is a lactate transporter that plays a central role in tumor pH modulation. The discovery and optimization of a novel class of MCT4 inhibitors (hit ), identified by a cellular screening in MDA-MB-231, is described.