Identification of novel tetrahydroquinoxaline derived phenyl ureas as modulators of the hepatitis B virus nucleocapsid assembly.

A key step of hepatitis B virus (HBV) replication is the selective packaging of pregenomic RNA (pgRNA) by core protein (Cp) dimers, forming a nucleocapsid where the reverse transcriptional viral DNA replication takes place. One approach in the development of new anti-HBV drugs is to disrupt the assembly of HBV nucleocapsids by misdirecting Cp dimers to assemble morphologically normal capsids devoid of pgRNA. In this study, we built upon our previous discovery of benzamide-derived HBV capsid assembly modulators by exploring fused bicyclic scaffolds with an exocyclic amide that is β, γ to the fused ring, and identified 1,2,3,4-tetrahydroquinoxaline derived phenyl ureas as a novel scaffold.

Paxlovid for hospitalized COVID-19 patients with chronic kidney disease.

Background: COVID-19 causes significant mortality during the recent pandemic. Data regarding the effectiveness of Paxlovid on COVID-19 patients with chronic kidney disease (CKD, eGFR <90 ml/min) are limited.

Methods: A retrospective cohort study was performed on the clinical data of the hospitalized adult patients with confirmed COVID-19 infection collected at Renji Hospital from April 7, 2022 to June 21, 2022.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

Background: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function.

Methods: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission.

Contamination and transmission of Mycobacteria in indoor environments of public buildings.

Objectives: The aim of this study was to detect Mycobacterium tuberculosis complex, M. avium subsp. avium and M.

4-Oxooctahydroquinoline-1(2H)-carboxamides as hepatitis B virus (HBV) capsid core protein assembly modulators.

Hepatitis B virus (HBV) core protein, the building block of the HBV capsid, plays multiple roles in viral replication, and is an attractive target for development of antiviral agents with a new mechanism of action. In addition to the heteroaryldihydropyrimidines (HAPs), sulfamoylbenzamides (SBAs), dibenzothiazepine derivatives (DBTs), and sulfamoylpyrrolamides (SPAs) that inhibit HBV replication by modulation of viral capsid assembly and are currently under clinical trials for the treatment of chronic hepatitis B (CHB), other chemical structures with activity to modulate HBV capsid assembly have also been explored. Here we describe our continued optimization of a benzamide originating from our high throughput screening.

Monitoring the Effective Sterilization of Low-Temperature Hydrogen Peroxide Gas Plasma Sterilizers in 58 Hospitals - 22 PLADs, China, June 2015-December 2019.

What Is Already Known On This Topic?: Hydrogen peroxide sterilizeation is widely used for luminal devices. However, the low penetrability of the sterilant is of major concern.

What Is Added By This Report?: This report investigated the effective sterilization of low-temperature hydrogen peroxide gas plasma sterilizers and compared the applicability of different biological monitoring methods based on medical luminal devices.

Identification of hepatitis B virus core protein residues critical for capsid assembly, pgRNA encapsidation and resistance to capsid assembly modulators.

Assembly of hepatitis B virus (HBV) capsids is driven by the hydrophobic interaction of core protein (Cp) at dimer-dimer interface. Binding of core protein allosteric modulators (CpAMs) to a hydrophobic "HAP" pocket formed between the inter-dimer interface strengths the dimer-dimer interaction and misdirects the assembly of Cp dimers into non-capsid Cp polymers or morphologically normal capsids devoid of viral pregenomic (pg) RNA and DNA polymerase. In this study, we performed a systematic mutagenesis analysis to identify Cp amino acid residues at Cp dimer-dimer interface that are critical for capsid assembly, pgRNA encapsidation and resistance to CpAMs.

Synthesis of 4-oxotetrahydropyrimidine-1(2H)-carboxamides derivatives as capsid assembly modulators of hepatitis B virus.

We report herein the synthesis and evaluation of phenyl ureas derived from 4-oxotetrahydropyrimidine as novel capsid assembly modulators of hepatitis B virus (HBV). Among the derivatives, compound () and several analogs showed an activity of submicromolar EC against HBV and low cytotoxicities (>50 μM). Structure-activity relationship studies revealed a tolerance for an additional group at position 5 of 4-oxotetrahydropyrimidine.

Targeting the multifunctional HBV core protein as a potential cure for chronic hepatitis B.

The core (capsid) protein of hepatitis B virus (HBV) is the building block of nucleocapsids where viral DNA reverse transcriptional replication takes place and mediates virus-host cell interaction important for the persistence of HBV infection. The pleiotropic role of core protein (Cp) in HBV replication makes it an attractive target for antiviral therapies of chronic hepatitis B, a disease that affects more than 257 million people worldwide without a cure. Recent clinical studies indicate that core protein allosteric modulators (CpAMs) have a great promise as a key component of hepatitis B curative therapies.

Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids.

Hepatitis B virus (HBV) replicates its genomic DNA via viral DNA polymerase self-primed reverse transcription of a RNA pre-genome in the nucleocapsid assembled by 120 core protein (Cp) dimers. The arginine-rich carboxyl-terminal domain (CTD) of Cp plays an important role in the selective packaging of viral DNA polymerase-pregenomic (pg) RNA complex into nucleocapsid. Previous studies suggested that the CTD is initially phosphorylated at multiple sites to facilitate viral RNA packaging and subsequently dephosphorylated in association with viral DNA synthesis and secretion of DNA-containing virions.

[Study on effect of 3 types of drinking water emergent disinfection models in flood/waterlog areas].

Objective: To establish 3 drinking water emergent disinfection processing models, separated medicate dispensing, specific duty medicate dispensing, and centralized filtering, in flood/waterlog areas, and compare the effects of these 3 models on the drinking water disinfection processing.

Methods: From October to December, 2008, 18 villages were selected as the trial field in Yanglinwei town, Xiantao city, Hubei province, which were divided into three groups, separated medicate dispensing, specific duty medicate dispensing, and centralized filtering. Every 2 weeks, drinking water source water, yielding water of emergency central filtrate water equipment (ECFWE) and container water in the kitchen were sampled and microbe indices of the water sample, standard plate-count bacteria, total coliforms, thermotolerant coliform bacteria, Escherichia coli were measured.

[Investigation of toxigenic microcystis and microcystin pollution in Huayuankou Conservation Pool of Yellow River].

Objective: To investigate the contaminative, condition of planktonic algae, cyanobacteria, toxigenic microcystis and microcystin in Huayuankou Conservation Pool of Yellow River.

Methods: From March 2005 to January 2006, water samples were taken 15 times by 2. 5L plastic sampler from Huayuankou Conservation Pool.

[Isolation and purification and toxigenic characteristic identification of microcystis].

Objective: To establish methods of isolation and purification of microcystis, and to identify it's biological property.

Methods: By the means of 96 well microplates and utmost dilution, microcystis was isolated and purified from Xiliu Lake of Zhengzhou. Absorbency of isolated microcystis was determined by visble light spectrophotometric method, and it's growth curve was ploted, calculated growth rate constant and double time.

[Investigation of algae pollution in Xiliu Lake and identification of toxic cyanobacteria by whole-cell PCR].

Objective: To investigate the contaminative condition of the floating algae (especially toxic cyanobacteria) in Xiliu Lake, and establish a whole-cell PCR method for identifying the toxic cyanobacteria.

Methods: The surface water of Xiliu Lake was sampled by plastic sampler from March, 2004, and the number of algae was counted by using blood cell counter. The phycocyanin intergenic spacer region (PC-IGS) and microcystin synthetase gene B (mcyB) were identified by whole-cell PCR in water samples, and the amplified product of mcyB was inserted into T vector and sequenced.