Study on The Current Status and Progress of Clinical Application of Ciprofol

Ciprofol,as a new type of short-acting intravenous anesthetic drug,belongs to the category of gamma-aminobutyric acid(GABA)receptor agonists.Its unique chemical structure,through the introduction of the cyclopropyl group in the isopropyl side chain of propofol,constructs a new type of chiral molecule,which significantly enhances the spatial effect,and improves the affinity for GABA receptors.Its pharmacological properties are characterized by high potency,rapid onset of action,rapid recovery,low accumulation,and minimal adverse reactions.Therefore,it has a wide range of applications in various endoscopic diagnostic and therapeutic operations,ICU sedation,and general anesthesia.In this paper,the related knowledge of ciprofol and the development of clinical application research are comprehensively sorted out and synthesized,to provide a solid theoretical basis for the rational application of ciprofol in clinical practice.At the same time,the future research direction of ciprofol will also be prospected to provide valuable references for research in related fields.

Understanding the phase separation characteristics of nucleocapsid protein provides a new therapeutic opportunity against SARS-CoV-2

Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COVID-19).As a newly emerged member of the coronavirus family,SARS-CoV-2 is an enveloped positive-strand RNA virus,which has probably the largest genome(approximately 30 kb)among all RNA viruses.The nucleocapsid(N)protein of SARS-CoV-2 is mainly responsible for recognizing and wrapping viral RNA into helically symmetric structures(Malik,2020).

Restoration of HBV-specific CD8+T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-αtherapy

Patients with chronic hepatitis B(CHB)undergoing interferon(IFN)-α-based therapies often exhibit a poor HBeAg serological response.Thus,there is an unmet need for new therapies aimed at CHB.This study comprised two clinical trials,including 130 CHB patients,who were treatment-naïve;in the first,92 patients were systematically analyzed ex vivo for interleukin-2 receptor(IL-2R)expression and inhibitory molecules expression after receiving Peg-IFN-α-2b therapy.In our second clinical trial,38 non-responder patients,in whom IFN-αtherapy had failed,were treated with or without low-dose IL-2 for 24 weeks.We then examined the hepatitis B virus(HBV)-specific CD8+T-cell response and the clinical outcome,in these patients.Although the majority of the participants undergoing Peg-IFN-α-2b therapy were non-responders,we observed a decrease in CD25 expression on their CD4+T cells,suggesting that IFN-αtherapy may provide a rationale for sequential IL-2 treatment without increasing regulatory T cells(Tregs).Following sequential therapy with IL-2,we demonstrated that the non-responders experienced a decrease in the numbers of Tregs and programmed cell death protein 1(PD-1)expression.In addition,sequential IL-2 administration rescued effective immune function,involving signal transducer and activator of transcription 1(STAT1)activation.Importantly,IL-2 therapy significantly increased the frequency and function of HBV-specific CD8+T cells,which translated into improved clinical outcomes,including HBeAg seroconversion,among the non-responder CHB patients.Our findings suggest that sequential IL-2 therapy shows efficacy in rescuing immune function in non-responder patients with refractory CHB.

An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

The global spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019(COVID-19).In this study,we developed an integrative drug repositioning framework,which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph,literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2.Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1(PARP1)inhibitor,CVL218,currently in Phase I clinical trial,may be repurposed to treat COVID-19.Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect.In addition,we showed that CVL218 can interact with the nucleocapsid(N)protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.