Miz1 represses type I interferon production and limits viral clearance during influenza A virus infection.

Type I interferons (IFNs) are critical for the antiviral immune response, and fine-tuning type I IFN production is critical to effectively clearing viruses without causing harmful immunopathology. We showed that the transcription factor Miz1 epigenetically repressed the expression of genes encoding type I IFNs in mouse lung epithelial cells by recruiting histone deacetylase 1 (HDAC1) to the promoters of and . Loss of function of Miz1 resulted in augmented production of these type I IFNs during influenza A virus (IAV) infection, leading to improved viral clearance in vitro and in vivo.

Identification of phytochemicals in Qingfei Paidu decoction for the treatment of coronavirus disease 2019 by targeting the virus-host interactome.

Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of COVID-19 by targeting the virus-host interactome and verifying the antiviral activities of its active components in vitro.

Discovery and optimization of new 6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline derivatives as potent influenza virus PA inhibitors.

Annual unpredictable efficacy of vaccines, coupled with emerging drug resistance, underlines the development of new antiviral drugs to treat influenza infections. The N-terminal domain of the PA (PA) endonuclease is both highly conserved across influenza strains and serotypes and is indispensable for the viral lifecycle, making it an attractive target for new antiviral therapies. Here, we describe the discovery of a new class of PA inhibitors derived from recently identified, highly active hits for PA endonuclease inhibition.

Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold.

Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold.

Essential Oil-Rich Chinese Formula Luofushan-Baicao Oil Inhibits the Infection of Influenza A Virus through the Regulation of NF-B P65 and IRF3 Activation.

Background: Luofushan-Baicao Oil (LBO) is an essential oil-rich traditional Chinese medicine (TCM) formula that is commonly used to treat cold, cough, headache, sore throat, swelling, and pain. However, the anti-influenza activities of LBO and the underlying mechanism remain to be investigated.

Methods: The anti-influenza activity of LBO was tested with methyl thiazolyl tetrazolium (MTT) and plaque assays.

Molecular Insight into the Adsorption Thermodynamics and Interfacial Behavior of GOs at the Liquid-Liquid Interface.

The adsorption of two-dimensional (2-D) graphene oxide (GO) nanosheets at liquid-liquid interfaces has broad technological implications from functional material preparations to oil-water emulsification. Molecular-level understanding of the adsorption thermodynamics and the interfacial behavior is of great significance. Here, the adsorption free energy of GO nanosheets at the water-cyclohexane system was simulated, in which the effect of oxygen-containing groups and deprotonation has been investigated.

Inducible Guanylate-Binding Protein 7 Facilitates Influenza A Virus Replication by Suppressing Innate Immunity via NF-κB and JAK-STAT Signaling Pathways.

Guanylate-binding protein 7 (GBP7) belongs to the GBP family, which plays key roles in mediating innate immune responses to intracellular pathogens. Thus far, GBP7 has been reported to be a critical cellular factor against bacterial infection. However, the relationship between GBP7 and influenza A virus (IAV) replication is unknown.

SNW1 interacts with IKKγ to positively regulate antiviral innate immune responses against influenza A virus infection.

The Ski-interacting protein (SNW1) acts as a transcriptional co-regulator associated with mRNA splicing and transcription, cell cycle progression, acute and chronic inflammatory responses, however, its role involved in host antiviral innate immune responses remains to be explored. Here, for the first time, we demonstrated that SNW1 positively regulates the expression of pro-inflammatory cytokines and interferon (IFN) responses induced by influenza A virus (IAV) infection, and further inhibits virus replication by performing SNW1 depletion or overexpression approaches. Furthermore, we showed that reduced interferon beta (IFN-β) expression caused by interfering SNW1 impairs the activation of JAK-STAT pathway in response to IAV or poly I:C.

Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a "Tail Switching" Strategy on a Piperazinyl Azetidine Skeleton.

Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold.