Recent advances of phenotypic screening strategies in the application of anti-influenza virus drug discovery.

Seasonal and pandemic influenza virus infections not only pose a serious threat to human health but also cause tremendous economic losses and social burdens. However, due to the inherent high variability of influenza virus RNA genomes, the existing anti-influenza virus drugs have been frequently faced with the clinical issue of emerging drug-resistant mutants. Therefore, there is an urgent need to develop efficient and broad-spectrum antiviral agents against wild-type and drug-resistant mutant strains.

A novel synthetic method for backbone-cyclized polypeptide POL7080 with the help of hydrophobic-support materials.

Murepavadin (POL7080) in phase III clinical trials, a backbone-cyclized polypeptide composed of 14 amino acids, has a novel mode of action and shows a specific and efficient bactericidal effect against multidrug-resistant . It is a potential candidate to treat severe infections in the future and still has significant commercial value for further research and development. In this paper, we report a liquid-phase peptide synthetic route for this valuable candidate polypeptide assisted by hydrophobic-support materials (tags), which overcomes the difficulties of high cost and poor yield in the traditional solid-phase synthesis of macrocyclic peptides.

Discovery of carboxyl-containing heteroaryldihydropyrimidine derivatives as novel HBV capsid assembly modulators with significantly improved metabolic stability.

Interfering with the assembly of hepatitis B virus (HBV) capsid is a promising approach for treating chronic hepatitis B (CHB). In order to enhance the metabolic stability and reduce the strong hERG inhibitory effect of HBV capsid assembly modulator (CAM) GLS4, we rationally designed a series of carboxyl-containing heteroaryldihydropyrimidine (HAP) derivatives based on structural biology information combined with medicinal chemistry strategies. The results from biological evaluation demonstrated that compound 6a-25 (EC = 0.

Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors click-chemistry-based rapid screening.

SARS-CoV-2 3-chymotrypsin-like protease (3CL) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The -substituted isatin derivative L-26 is a potential SARS-CoV-2 3CL inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58 isatin derivatives were prepared using click-chemistry-based miniaturized synthesis and their 3CL inhibitory activities were determined by a fluorescence resonance energy transfer-based enzymatic assay.

Design, synthesis, and mechanistic study of 2-piperazineone-bearing peptidomimetics as novel HIV capsid modulators.

HIV-1 capsid (CA) is an attractive target for its indispensable roles in the viral life cycle. We report the design, synthesis, and mechanistic study of a novel series of 2-piperazineone peptidomimetics as HIV capsid modulators by mimicking the structure of host factors binding to CA. F-Id-3o was the most potent compound from the synthesized series, with an anti-HIV-1 EC value of 6.

A Series of Adenosine Analogs as the First Efficacious Anti-SARS-CoV-2 Drugs against the B.1.1.529.4 Lineage: A Preclinical Repurposing Research Study.

Given the rapid progression of the coronavirus disease 2019 (COVID-19) pandemic, an ultrafast response was urgently required to handle this major public crisis. To contain the pandemic, investments are required to develop diagnostic tests, prophylactic vaccines, and novel therapies. Lately, nucleoside analog (NA) antivirals topped the scene as top options for the treatment of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.

Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis.

Aminopeptidase N is considered as a promising anti-tumor target due to its role in tumor invasion, metastasis and angiogenesis. In this report, a new series of pyrazoline-based derivatives were designed, synthesized and evaluated for biological activities. The structure-activity relationships of these pyrazoline-based derivatives were also discussed in detail.

Multipoint Costriking Nanodevice Eliminates Primary Tumor Cells and Associated-Circulating Tumor Cells for Enhancing Metastasis Inhibition and Therapeutic Effect on HCC.

Eliminating primary tumor ("roots") and inhibiting associated-circulating tumor cells (associated-CTCs, "seeds") are vital issues that need to be urgently addressed in cancer therapy. Associated-CTCs, which include single CTCs, CTC clusters, and CTC-neutrophil clusters, are essential executors in metastasis and the cause of metastasis-related death in cancer patients. Herein, a "roots and seeds" multipoint costriking nanodevice (GV-Lipo/sorafenib (SF)/digitoxin (DT)) is developed to eliminate primary tumors and inhibit the spread of associated-CTCs for enhancing metastasis inhibition and the therapeutic effect on hepatocellular carcinoma (HCC).

Epimedokoreanin C, a prenylated flavonoid isolated from , induces non-apoptotic cell death with the characteristics of methuosis in lung cancer cells.

Methuosis is a novel type of non-apoptotic cell death characterized by accumulation of cytoplasmic vacuoles. Identification of molecules that induce methuosis may provide alternative therapeutics for cancers that are refractory to apoptosis. Epimedokoreanin C (EKC) is a prenylated flavonoid isolated from a Chinese herb .

Correction: Single-molecule FRET and conformational analysis of beta-arrestin-1 through genetic code expansion and a Se-click reaction.

[This corrects the article DOI: 10.1039/D1SC02653D.].

Single-molecule FRET and conformational analysis of beta-arrestin-1 through genetic code expansion and a Se-click reaction.

Single-molecule Förster resonance energy transfer (smFRET) is a powerful tool for investigating the dynamic properties of biomacromolecules. However, the success of protein smFRET relies on the precise and efficient labeling of two or more fluorophores on the protein of interest (POI), which has remained highly challenging, particularly for large membrane protein complexes. Here, we demonstrate the site-selective incorporation of a novel unnatural amino acid (2-amino-3-(4-hydroselenophenyl) propanoic acid, SeF) through genetic expansion followed by a Se-click reaction to conjugate the Bodipy593 fluorophore on calmodulin (CaM) and β-arrestin-1 (βarr1).

Charge and Size Dual Switchable Nanocage for Novel Triple-Interlocked Combination Therapy Pattern.

Combination therapy is a current hot topic in cancer treatment. Multiple synergistic effects elicited by combined drugs are essential in improving antitumor activity. Herein, a pH-triggered charge and size dual switchable nanocage co-loaded with abemaciclib and IMD-0354 (PA/PI-ND) is reported, exhibiting a novel triple-interlocked combination of chemotherapy, immunotherapy, and chemoimmunotherapy.

Simple weak-acid derivatives of paclitaxel for remote loading into liposomes and improved therapeutic effects.

Liposomes are among the most successful nanocarriers; several products have been marketed, all of which were prepared by active loading methods. However, poorly water-soluble drugs without ionizable groups are usually incorporated into the lipid bi-layer of liposomes by passive loading methods, with serious drug leakage during blood circulation. Furthermore, there have been few improvements in their anti-cancer activity and safety.

Rational design of a new cytarabine-based prodrug for highly efficient oral delivery of cytarabine.

Because of the drawbacks of cytarabine (Ara-C) such as poor lipid solubility, deamination inactivation and low oral bioavailability limiting its application by oral administration, herein we propose a novel amphiphilic low molecular weight cytarabine prodrug (PA-Ara) by conjugating palmitic acid (PA) to Ara-C, making it possible to avoid the deamination inactivation by protecting the active 4-amino, as well as improving lipid solubility. Thanks to the rational design, the oil/water partition coefficient () of PA-Ara was improved tremendously compared with Ara-C, and the PA-Ara conjugation was stable enough in artificial digestive juice, ensuring that most molecules could be absorbed in the form of the prodrug. Results from an MTT assay conducted to measure the cytotoxicity of Ara-C and PA-Ara to HL60 (acute myeloblastic leukemia cell line) and K562 cells (chronic granulocytic leukemia cell line) showed that PA-Ara had significantly stronger antiproliferation activities than Ara-C.

l-Menthol alleviates cigarette smoke extract induced lung injury in rats by inhibiting oxidative stress and inflammation nuclear factor kappa B, p38 MAPK and Nrf2 signalling pathways.

l-Menthol is the main ingredient of peppermint which affects various pharmacological effects such as anti-inflammation and anti-oxidative activity. In this study, we aimed to evaluate the potential effects of l-menthol on cigarette smoke extract (CSE) induced lung injury in rats. Morphology assessment results revealed that administration with l-menthol (5, 10 or 20 mg kg d) significantly alleviated CSE-induced lung injury.

The Design of Amphiphilic Polymeric Micelles of Curcumin for Cancer Management.

Curcumin, a natural phenolic compound mainly extracted from turmeric curcuma longa, has been employed to prevent or treat plenty of diseases particularly cancer. It has been proven to modulate various signal transduction pathways and exhibits antiinflammatory, anti-oxidative, anti-metastasis anti-proliferative, anti-angiogenic in addition anti-cancer activities. However, its poor solubility and rapid degradation severely hampers the introduction into clinical setting.

IL-17A G197A gene polymorphism contributes to susceptibility for liver cirrhosis development from patients with chronic hepatitis B infection in Chinese population.

Background: IL-17A G197A and IL-17F A7488G gene polymorphisms are found to be associated with the risk of several diseases, however few studies have focused on their correlation with risk of liver cirrhosis (LC).

Aims: The aim of this study was to assess the impact of IL-17A G197A and IL-17F A7488G gene polymorphisms on development of LC from chronic hepatitis B (CHB) in Chinese patients.

Methods: A total of 163 HBV-related LC patients and 168 CHB patients were enrolled in the present study.

Expression of CXCR4 and non-small cell lung cancer prognosis: a meta-analysis.

Purpose: The prognostic value of aberrant C-X-C chemokine receptor type 4 (CXCR4) levels in NSCLC has been described in empirical studies. This meta-analysis evaluates the value of CXCR4 as a prognostic marker for NSCLC and determines the relationship between CXCR4 and clinicopathological features of NSCLC.

Methods: A comprehensive search of the English-language literature in PubMed, Embase, Google Scholar and Web of Science was performed.

A novel approach using Neuron 6F guiding catheter for the embolization of intracranial aneurysm with coiling of the parent internal carotid artery.

To describe our initial experience and early outcomes with distal placement of the Neuron 6F guiding catheter through coiled ICA for aneurysmal EVT. We examined the utility of the Neuronf 70 6F guiding catheter for the embolization procedure in such cases, fourteen cases of aneurysm with coiling of the parent ICA are presented via traditional guiding catheters. With the support of 8F ENVOY guiding catheter as a shuttle sheath, the Neuron(TM) 70 6F guiding catheter was successfully placed through coiled extracranial ICA, so the mirocatheter could be delivered to a more strategic position for embolization of the aneurysm.

Cerium promotes bone marrow stromal cells migration and osteogenic differentiation via Smad1/5/8 signaling pathway.

Cerium (Ce), one of the lanthanides (Ln), displays a variety of biochemical and physiological effects. However, the potential effect and mechanism of Ce on bone metabolism are not well understood. In this study, we investigated the putative role of Ce in regulating the migration and osteogenic differentiation of bone marrow stromal cells (BMSCs) and the underlying mechanism.

Opposing effect of IFNgamma and IFNalpha on expression of NKG2 receptors: negative regulation of IFNgamma on NK cells.

The effector functions of natural killer (NK) cells are regulated by integrated signals across an array of stimulatory and inhibitory receptors interacting with target cell surface ligands. The regulatory effect of interferon-alpha (IFNalpha) and interferon-gamma (IFNgamma) on expression of the family of NKG2 receptors, stimulatory NKG2D receptor and inhibitory NKG2A receptor, and cytolysis of the target tumor cells (MICA+ and HLA-E+) were studied. Results show that IFNgamma and IFNalpha influence NK cell function differently.