Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein

The nucleocapsid protein(NP)plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long half-life.Despite its vital role in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)assembly and host inflammatory response,it remains an unexplored target for drug development.In this study,we identified a small-molecule compound(ciclopirox)that promotes NP degradation using an FDA-approved library and a drug-screening cell model.Ciclopirox significantly inhibited SARS-CoV-2 replication both in vitro and in vivo by inducing NP degradation.Ciclopirox induced abnormal NP aggregation through indirect interaction,leading to the formation of condensates with higher viscosity and lower mobility.These condensates were subsequently degraded via the autophagy-lysosomal pathway,ultimately resulting in a shortened NP half-life and reduced NP expression.Our results suggest that NP is a potential drug target,and that ciclopirox holds substantial promise for further development to combat SARS-CoV-2 replication.

Ligand enabled none-oxidative decarbonylation of aliphatic aldehydes

Decarbonylation of aldehydes is a basic organic transformation, which has been developed for more than six-decade. However, as comparing to well-studied aromatic aldehydes, fewer examples for catalytic decarbonylation of aliphatic aldehydes were reported, mainly on simple or special substrates.For α-bulky or highly functionalized ones, stoichiometric Rh(I) were usually required for decent yields.Herein, we present a rare example of Ir(I)-catalyzed direct decarbonylation of α-quaternary aldehydes with broad substrate scope and good functional group compatibility via judicious selection of ligand. Theα-chirality is memorized in this decarbonylation process. In addition, we report a broad-spectrum decarbonylation of α-secondary and α-tertiary aldehydes containing multifunctional groups with an improved Rh(I)/DPPP recipe. Finally, we realized selective decarbonylation of α-tertiary aldehydes in the presence of α-quaternary one via the reactivity differences.

Accelerated plasma degradation of organic pollutants in milliseconds and examinations by mass spectrometry

The rapid degradation of organic pollutants,process monitoring and online controlling to obtain advanced products and decreased by-products are great and challenging tasks in environmental treatments.Herein,an accelerated plasma degradation in milliseconds was achieved by combining electrospray-based acceleration and plasma-based degradation.Taking the degradation of chloroaniline as an example,97%of the degradation can be achieved in milliseconds.The velocity distribution of droplets was determined to be 40-50 m/s after being degraded for 0.30 ms,which exhibited different degradation behaviors in different milliseconds.Simultaneously,by virtue of the real-time and on-line detection ability of ambient mass spectrometry,intermediates,by-products and advanced products were monitored.Therefore,degradation mechanisms for different degradation times were proposed,which would provide theoretical guidance on obtaining efficient and green degradation.The fabrication,examining and understanding of accelerated plasma degradation not only enlarged application of accelerated reactions,but also promoted green and efficient degradation for environmental treatments.

Fluorescence resonance energy transfer-based nanomaterials for the sensing in biological systems

The applications of fluorescence resonance energy transfer(FRET)are coming to be one of the simplest and most accessible strategy with super-resolved optical measurements.Meanwhile,nanomaterials have become ideal for constructing FRET-based system,due to their unique advantages of tunable emission,broad absorption,and long fluorescence(FL)lifetime.The limitations of traditional FRET-based detections,such as the intrinsic FL,auto-FL,as well as the short FL lifetime,could be overcome with nanomaterials.Consequently,numbers of FRET-based nanomaterials have been constructed for precise,sensitive and selective detections in biological systems.They could act as both energy donors and/or acceptors in the optical energy transfer process for biological detections.Some other nanomaterials would not participate in the energy transfer process,but act as the excellent matrix for modifications.The review will be roughly classified into nanomaterial-involved and uninvolved ones.Different detection targets,such as nucleic acids,pathogenic microorganisms,proteins,heavy metal ions,and other applications will be reviewed.Finally,the other biological applications,including environmental evaluation and mechanism studies would also be summarized.