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Influenza A virus is the main cause of worldwide epidemics and annual influenza outbreaks in humans. In this study, a virtual screen was performed to identify compounds that interact with the PB2 cap-binding domain (CBD) of influenza A polymerase. A virtual screening workflow based on Glide docking was used to screen an internal database containing 8417 molecules, and then the output compounds were selected based on solubility, absorbance, and structural fingerprints. Of the 16 compounds selected for biological evaluation, six compounds were identified that rescued cells from H1N1 virus-mediated death at non-cytotoxic concentrations, with EC50 values ranging from 2.5–55.43 μM, and that could bind to the PB2 CBD of H1N1, with Kd values ranging from 0.081–1.53 μM. Molecular dynamics (MD) simulations of the docking complexes of our active compounds revealed that each compound had its own binding characteristics that differed from those of VX-787. Our active compounds have novel structures and unique binding modes with PB2 proteins, and are suitable to serve as lead compounds for the development of PB2 inhibitors. An analysis of the MD simulation also helped us to identify the dominant amino acid residues that play a key role in binding the ligand to PB2, suggesting that we should focus on increasing and enhancing the interaction between inhibitors and these major amino acids during lead compound optimization to obtain more active PB2 inhibitors.

The interaction between pyridoxal hydrochloride (HQ) and apoCopC was investigated using Fourier transform infrared spectroscopy (FTIR), isothermal titration calorimetry (ITC), circular dichroism (CD), fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy, fluorescence lifetime, TNS fluorescence and docking methods. FTIR, CD, TNS fluorescence and fluorescence lifetime experiments suggested that the apoCopC conformation was altered by HQ with an increase in the random coil content and a reduction in the β-sheet content. In addition, the data from fluorescence spectroscopy, 3D fluorescence spectroscopy and molecular docking revealed that the binding site of HQ was located in the hydrophobic area of apoCopC, and a redshift of the HQ fluorescence spectra was observed. Furthermore, ITC and fluorescence quenching data manifested that the binding ratio of HQ and apoCopC was 1:1, and the forming constant was calculated to be (7.06 ± 0.21) × 105 M−1. The thermodynamic parameters ΔH and ΔS suggested that the formation of a CopC-HQ complex depended on the hydrophobic force. Furthermore, the average binding distance between tryptophan in apoCopC and HQ was determined by means of Forster non-radioactive resonance energy transfer and molecular docking. The results agreed well with each other. As a redox switch in the modulation of copper, the interaction of apoCopC with small molecules will affect the action of the redox switch. These findings could provide useful information to illustrate the copper regulation mechanism.

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs., Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.

The ability of a flexible pressure sensor to possess zero power consumption in standby mode, high sensitivity, and wide linear-response range is critical in real flexible matrix-based scenes. However, when the conventional flexible pressure sensors are attached on a curved surface, a pseudosignal response is generated because of the normal stress, resulting in a short linear-response range. Here, a flexible piezoresistive pressure sensor with high performance, zero standby power consumption is demonstrated. The flexible pressure sensor is fabricated from polydimethylsiloxane (PDMS)/carbon black (CB), patterned polyimide (PI) spacer layer, and laser-induced graphene (LIG) interdigital electrodes. Benefiting from the hierarchical structure and sufficient roughness of PDMS/CB and LIG interdigital electrodes, the proposed pressure sensors (PDMS/CB/PI/LIG) exhibit high sensitivity (43 kPa-1), large linear-response range (0.4-13.6 kPa), fast response (1800 cycles). The resulting pressure sensor also features zero standby power consumption merit under certain bending conditions (bending angle: 0-5o). Furthermore, the effect of the hole diameter of the PI spacer layer on the performance of the pressure sensors is experimentally and theoretically investigated. As a proof of concept, a bioinspired artificial haptic neuron system has been successfully equipped to modulate the number of lit LED lights. The proposed high-performance pressure sensor has promising potential to be used in flexible and wearable electronics, especially for the applications in actual flexible matrix-based scenes. Ministry of Education (MOE) This work was partially supported by the National Key R&D Program of China (2018YFB1500200), Shenzhen Basic Research Grant: JCYJ20180507182431967, JCYJ20170413153246713, Shenzhen Peacock Technology Innovation Project: KQJSCX20170731165602155, the National Nature Science Foundation of China (11804354, 61574157, 61774164). The authors are also grateful for the support of Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2015-T2-2-010), and Singapore Ministry of Education Academic Research Fund Tier 1 (MOE2019-T1-001-103).

Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second, siRNA depletion of Hsp90β, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90β interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90β is required to maintain NP stability. Fourth, 17-AAG substantially inhibited the propagation of SARS-CoV and SARS-CoV-2. Collectively, Hsp90 is a host dependency factor for human coronavirus MERS-CoV, SARS-CoV and SARS-COV-2. Hsp90 inhibitors can be repurposed as a potent and broad-spectrum antiviral against human coronaviruses.

We propose a novel electrochemical method to one-pot synthesize carbon dots/titanium dioxide (CDs/TiO 2 ) nanocomposites for the first time. The as-prepared CDs/TiO 2 nanocomposites exhibit excellent visible photocatalytic activity for degradation of methylene blue (MB) under a 50 W halogen tungsten lamp irradiation.

The recent advancement of flexible pressure sensors leads to promising applications in electronic skins for human-machine interaction and bionic device for intelligent wearable field. The abilities of such sensors to possess zero power consumption in standby mode, high sensitivity and wide linear response range are critical yet highly desirable in real flexible-matrix-based scenes. Despite the myriad of the existing approaches, it is still challenging to fulfill these requirements simultaneously in a single pressure sensor. Herein, we demonstrate a high-performance, zero-standby-power-consumption flexible pressure sensor by introducing a tunable photoresist spacer (PS) sandwiched between the top truncated-pyramid microstructure polydimethylsiloxane (PDMS)/aluminum-doped zinc oxide (AZO) and the bottom polyimide (PI)/gold (Au) interdigital electrode (PDMS-AZO/PS/PI-Au). The fabricated pressure sensor is equipped with bending-insensitive and zero-power-consumption merit under the bending angle of less than 20.5° benefiting from the insulation effect of PS. As a result, the fabricated sensor exhibits ultrahigh sensitivity of 2200 kPa−1 in the ultrawide linear response range of 62 Pa-9.6 kPa and fast response and recovery time (

Ultrathin graphitic carbon nitride nanosheets (g-C3N4) with a thickness of about 2 nm were synthesized by a one-step electrochemical method for the first time. The possible mechanism of the electrochemical synthesis was discussed. This as-synthesized g-C3N4 showed intrinsic peroxidase-like activity and was successfully applied for the detection of uric acid.

Sulfur, nitrogen co-doped carbon dots (S, N co-doped C-dots) as highly selective fluorescent probe for uric acid (UA) detection were designed. The S, N co-doped C-dots with high quantum yield of 73.1% were prepared by hydrothermal method. It was found that the fluorescence of S, N co-doped C-dots was quenched apparently by hydroxyl radicals from Fenton reaction between H2O2 and Fe(2+). The production of H2O2 originated from the oxidization of UA by uricase. Therefore, an optical biosensor was developed for the detection of UA based on Fenton reaction and enzymatic reaction. Under the optimized conditions, two linear relationships between the ratio of fluorescence quenching of the C-dots and UA concentration were found in the range of 0.08-10µM and 10-50µM, respectively. The detection limit was down to 0.07µM. Moreover, the proposed biosensor was successfully applied to the detection of uric acid in human serum samples.

The graphitic carbon nitride nanodots (g-C3N4-dots) were synthesized by a simple electrochemical "tailoring" process from bulk graphitic carbon nitride (g-C3N4) under alkaline solution for the first time. Compared with the bulk g-C3N4, the novel g-C3N4-dots not only exhibit enhanced fluorescence and excellent dispersion stability in water but also show the reducibility for the reduction of Ag+ to AgNPs at 60°C. The biothiols can bound with Ag+ through formation of biothiol-Ag+ complex to consume the Ag+ and act as capping agent to prevent the growth of AgNPs, which cause the decrease of the absorption peak of the AgNPs. Therefore, an optical sensor was developed for the detection of biothiols based on the change of the plasmon resonance absorption peak of the AgNPs. The proposed method exhibits excellent sensitivity and selectivity to biothiols with low detection limit for cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) with 11.5, 16.1, and 15.5nM, respectively. This method also has been successfully applied for the detection of biothiols in human serum with satisfactory results.

We have found that hydroxyl-rich carbon dots (C-dots) have the ability to reduce Au(3+) to form gold nanoparticles (AuNPs). Thiocyanate (SCN(-)) can be absorbed on the surface of the AuNPs due to its high affinity toward the AuNPs, which inhibits the growth of the AuNPs. Meanwhile, SCN(-) has the ability to etch the as-synthesized big AuNPs to small AuNPs, which can also cause the absorption peak of the AuNPs to decrease. Therefore, an optical sensor is developed for the detection of SCN(-) based on measuring the plasmon resonance absorption peak change of the AuNPs. Under optimal conditions, this method yields excellent sensitivity (the limit of detection is 0.16 μM) and selectivity toward SCN(-). This method can detect SCN(-) in raw milk with satisfactory results. This work gives new insight into monitoring the quality of milk.

Hydro-rich C-dots were used as both the reducing and stabilizing agent in the preparation of noble metal nanoparticles (AuNPs, AgNPs and Au@AgNPs) for the detection of glucose.

Biological thiols play a critical role in biological processes and are involved in a variety of diseases. The discrimination detection of biological thiols is of increasing importance in clinical diagnosis. In this paper, a novel nanosensor was developed to discriminate cysteine (Cys) from homocysteine (Hcy) and glutathione (GSH) with multiple signals: colorimetric, photoluminescence (PL), and up-conversional photoluminescence (UCP). The nanosensor (NC-dots/AuNPs) was constructed by nitrogen-doped carbon dots (NC-dots) and gold nanoparticles (AuNPs) through assembling NC-dots "shell" on AuNPs and showed the obvious different response to Cys, Hcy, and GSH with colorimetric, PL, and UCP signals. The discrimination effect for Cys is originated from conformations and interaction difference of the thiols groups in Cys and Hcy and/or GSH with AuNPs. Among them, only Cys can quickly penetrate into the NC-dots "shell" of the composite and induce the dispersing of the aggregated NC-dots/AuNPs, which lead to the color change from purple to red and the recovery of PL and UCP of NC-dots. This assay was successfully applied for the detection of Cys in human serum with the detection limit of 4 nM.

We propose a simple, economical, and one-pot method to synthesize water-soluble functionalized fluorescent carbon dots (C-Dots) through electrochemical carbonization of sodium citrate and urea. The as-prepared C-Dots have good photostability and exhibit a high quantum yield of 11.9%. The sizes of the C-Dots are mainly distributed in the range of 1.0-3.5 nm with an average size of 2.4 nm. It has been further used as a novel label-free sensing probe for selective detection of Hg(2+) ions with detection limit as low as 3.3 nM. The detection linear range is 0.01-10 μM. The as-prepared C-Dots are also successfully applied for the determination of Hg(2+) in real water samples.