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Showing papers by "Nankai University published in 2020"


Journal ArticleDOI
11 Jun 2020-Nature
TL;DR: A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.
Abstract: A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019–2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)1–4. Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (Mpro) of SARS-CoV-2: Mpro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-25,6. We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of Mpro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds—including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds—as inhibitors of Mpro. Six of these compounds inhibited Mpro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 μM. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available. A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.

2,845 citations


Journal ArticleDOI
Xuetao Cao1
TL;DR: Defining the immunopathological changes in patients with COVID-19 provides potential targets for drug discovery and is important for clinical management.
Abstract: Severe coronavirus disease 2019 (COVID-19) is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Significant antibody production is observed; however, whether this is protective or pathogenic remains to be determined. Defining the immunopathological changes in patients with COVID-19 provides potential targets for drug discovery and is important for clinical management. In the short time since SARS-CoV2 emerged, much has been learned about the immunopathology of the infection. Here, Xuetao Cao discusses what these early insights imply for drug discovery and clinical management.

1,244 citations


Journal ArticleDOI
10 Apr 2020-Science
TL;DR: The structure of the COVID-19 virus polymerase essential for viral replication provides a basis for the design of new antiviral drugs that target viral RdRp, also named nsp12, and it appears to be a primary target for the antiviral drug remdesivir.
Abstract: A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-A resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified β-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics targeting viral RdRp.

1,180 citations


Journal ArticleDOI
TL;DR: A deep residual network for predicting interresidue orientations, in addition to distances, and a Rosetta-constrained energy-minimization protocol for rapidly and accurately generating structure models guided by these restraints are developed.
Abstract: The prediction of interresidue contacts and distances from coevolutionary data using deep learning has considerably advanced protein structure prediction. Here, we build on these advances by developing a deep residual network for predicting interresidue orientations, in addition to distances, and a Rosetta-constrained energy-minimization protocol for rapidly and accurately generating structure models guided by these restraints. In benchmark tests on 13th Community-Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP13)- and Continuous Automated Model Evaluation (CAMEO)-derived sets, the method outperforms all previously described structure-prediction methods. Although trained entirely on native proteins, the network consistently assigns higher probability to de novo-designed proteins, identifying the key fold-determining residues and providing an independent quantitative measure of the "ideality" of a protein structure. The method promises to be useful for a broad range of protein structure prediction and design problems.

1,026 citations


Journal ArticleDOI
19 Jun 2020-Science
TL;DR: Two peptidomimetic aldehydes were designed, synthesized, and evaluated as antiviral drug candidates, and both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity.
Abstract: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of 11a and 11b are covalently bound to cysteine 145 of Mpro Both compounds showed good pharmacokinetic properties in vivo, and 11a also exhibited low toxicity, which suggests that these compounds are promising drug candidates.

1,023 citations


Journal ArticleDOI
Hongming Sun1, Zhenhua Yan1, Fangming Liu1, Wence Xu1, Fangyi Cheng1, Jun Chen1 
TL;DR: Focusing on self-supported electrodes, the latest advances in their structural design, controllable synthesis, mechanistic understanding, and strategies for performance enhancement are presented.
Abstract: Electrochemical water splitting is a promising technology for sustainable conversion, storage, and transport of hydrogen energy. Searching for earth-abundant hydrogen/oxygen evolution reaction (HER/OER) electrocatalysts with high activity and durability to replace noble-metal-based catalysts plays paramount importance in the scalable application of water electrolysis. A freestanding electrode architecture is highly attractive as compared to the conventional coated powdery form because of enhanced kinetics and stability. Herein, recent progress in developing transition-metal-based HER/OER electrocatalytic materials is reviewed with selected examples of chalcogenides, phosphides, carbides, nitrides, alloys, phosphates, oxides, hydroxides, and oxyhydroxides. Focusing on self-supported electrodes, the latest advances in their structural design, controllable synthesis, mechanistic understanding, and strategies for performance enhancement are presented. Remaining challenges and future perspectives for the further development of self-supported electrocatalysts are also discussed.

1,015 citations


Journal ArticleDOI
TL;DR: There is a high prevalence of psychological health problems among adolescents, which are negatively associated with the level of awareness of CO VID-19, and the government needs to pay more attention to psychological health among adolescents while combating COVID-19.
Abstract: Psychological health problems, especially emotional disorders, are common among adolescents. The epidemiology of emotional disorders is greatly influenced by stressful events. This study sought to assess the prevalence rate and socio-demographic correlates of depressive and anxiety symptoms among Chinese adolescents affected by the outbreak of COVID-19. We conducted a cross-sectional study among Chinese students aged 12-18 years during the COVID-19 epidemic period. An online survey was used to conduct rapid assessment. A total of 8079 participants were involved in the study. An online survey was used to collect demographic data, assess students' awareness of COVID-19, and assess depressive and anxiety symptoms with the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) questionnaire, respectively. The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 43.7%, 37.4%, and 31.3%, respectively, among Chinese high school students during the COVID-19 outbreak. Multivariable logistic regression analysis revealed that female gender was the higher risk factor for depressive and anxiety symptoms. In terms of grades, senior high school was a risk factor for depressive and anxiety symptoms; the higher the grade, the greater the prevalence of depressive and anxiety symptoms. Our findings show there is a high prevalence of psychological health problems among adolescents, which are negatively associated with the level of awareness of COVID-19. These findings suggest that the government needs to pay more attention to psychological health among adolescents while combating COVID-19.

857 citations


Journal ArticleDOI
T. Aoyama1, Nils Asmussen2, M. Benayoun3, Johan Bijnens4  +146 moreInstitutions (64)
TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon is reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice approach.

801 citations


Journal ArticleDOI
TL;DR: This review attempts to highlight the key advancements made in the synthesis of COFs for diverse separation applications such as water treatment or the separation of gas mixtures and organic molecules, including chiral and isomeric compounds.
Abstract: Covalent organic frameworks (COFs) are an emerging class of crystalline porous polymers with highly tuneable structures and functionalities. COFs have been proposed as ideal materials for applications in the energy-intensive field of molecular separation due to their notable intrinsic features such as low density, exceptional stability, high surface area, and readily adjustable pore size and chemical environment. This review attempts to highlight the key advancements made in the synthesis of COFs for diverse separation applications such as water treatment or the separation of gas mixtures and organic molecules, including chiral and isomeric compounds. Methods proposed for the fabrication of COF-based columns and continuous membranes for practical applications are also discussed in detail. Finally, a perspective regarding the remaining challenges and future directions for COF research in the field of separation has also been presented.

599 citations


Journal ArticleDOI
Yong Lu1, Jun Chen1
01 Mar 2020
TL;DR: In this paper, the authors provide an overview of the history and redox of organic electrode materials and then evaluate the prospects and remaining challenges of organic electrode materials for practical lithium batteries.
Abstract: Organic materials have attracted much attention for their utility as lithium-battery electrodes because their tunable structures can be sustainably prepared from abundant precursors in an environmentally friendly manner. Most research into organic electrodes has focused on the material level instead of evaluating performance in practical batteries. This Review addresses this by first providing an overview of the history and redox of organic electrode materials and then evaluating the prospects and remaining challenges of organic electrode materials for practical lithium batteries. Our evaluations are made according to energy density, power density, cycle life, gravimetric density, electronic conductivity and other relevant parameters, such as energy efficiency, cost and resource availability. We posit that research in this field must focus more on the intrinsic electronic conductivity and density of organic electrode materials, after which a comprehensive optimization of full batteries should be performed under practically relevant conditions. We hope to stimulate high-quality applied research that might see the future commercialization of organic electrode materials. Organic materials can serve as sustainable electrodes in lithium batteries. This Review describes the desirable characteristics of organic electrodes and the corresponding batteries and how we should evaluate them in terms of performance, cost and sustainability.

595 citations


Journal ArticleDOI
TL;DR: This tutorial review presents an introduction to the fundamentals, challenges, recent advances and prospects related to ZIBs.
Abstract: Rechargeable zinc-ion batteries (ZIBs) are promising for large scale energy storage and portable electronic applications due to their low cost, material abundance, high safety, acceptable energy density and environmental friendliness. This tutorial review presents an introduction to the fundamentals, challenges, recent advances and prospects related to ZIBs. Firstly, the intrinsic chemical properties, challenges and strategies of metallic zinc anodes are underscored. Then, the multiple types of cathode materials are classified and comparatively discussed in terms of their structural and electrochemical properties, issues and remedies. Specific attention is paid to the mechanistic understanding and structural transformation of cathode materials based on Zn ion-(de)intercalation chemistry. After that, the widely investigated electrolytes are elaborated by discussing their effect on Zn plating/stripping behaviours, reaction kinetics, electrode/electrolyte interface chemistries, and cell performances. Finally, the remaining challenges and future perspectives are outlined for the development of ZIBs.

Journal ArticleDOI
TL;DR: It is found that average temperature, minimum temperature, and air quality were significantly associated with the COVID-19 pandemic.

Journal ArticleDOI
T. Aoyama1, Nils Asmussen2, M. Benayoun3, Johan Bijnens4  +146 moreInstitutions (64)
TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon has been reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach.
Abstract: We review the present status of the Standard Model calculation of the anomalous magnetic moment of the muon. This is performed in a perturbative expansion in the fine-structure constant $\alpha$ and is broken down into pure QED, electroweak, and hadronic contributions. The pure QED contribution is by far the largest and has been evaluated up to and including $\mathcal{O}(\alpha^5)$ with negligible numerical uncertainty. The electroweak contribution is suppressed by $(m_\mu/M_W)^2$ and only shows up at the level of the seventh significant digit. It has been evaluated up to two loops and is known to better than one percent. Hadronic contributions are the most difficult to calculate and are responsible for almost all of the theoretical uncertainty. The leading hadronic contribution appears at $\mathcal{O}(\alpha^2)$ and is due to hadronic vacuum polarization, whereas at $\mathcal{O}(\alpha^3)$ the hadronic light-by-light scattering contribution appears. Given the low characteristic scale of this observable, these contributions have to be calculated with nonperturbative methods, in particular, dispersion relations and the lattice approach to QCD. The largest part of this review is dedicated to a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach. The final result reads $a_\mu^\text{SM}=116\,591\,810(43)\times 10^{-11}$ and is smaller than the Brookhaven measurement by 3.7$\sigma$. The experimental uncertainty will soon be reduced by up to a factor four by the new experiment currently running at Fermilab, and also by the future J-PARC experiment. This and the prospects to further reduce the theoretical uncertainty in the near future-which are also discussed here-make this quantity one of the most promising places to look for evidence of new physics.

Journal ArticleDOI
TL;DR: Recent advances in the strategies for synthesizing MOFs with multiple emission centers and their applications for ratiometric sensing of solution conditions, including the pH value, and ion, organic molecule, and biomolecule concentrations, are summarized, as are the related sensing mechanisms.
Abstract: Metal-organic frameworks (MOFs) with multiple emission centers are newly emerging as ratiometric sensors owing to their high sensitivity and high selectivity toward a wide range of targeted functional species. Energy transfer between the light-absorbing group and emission centers and between different emission centers is the key to rationally design and synthesize MOF-based ratiometric sensors. A good match between the energy levels of the light-absorbing groups and emission centers is the prerequisite for MOF-based sensors to exhibit multiple emissions, and a good match of the MOF-based sensors and those of the targeted species can increase the sensitivity and selectivity, but this match is highly challenging to obtain via synthesis. MOFs with multiple emission centers can be produced by functionalizing MOFs with multiple lanthanide centers, organic luminophores, dyes, carbon dots, and other such emissive groups. In this progress report, recent advances in the strategies for synthesizing MOFs with multiple emission centers and their applications for ratiometric sensing of solution conditions, including the pH value, and ion, organic molecule, and biomolecule concentrations, are summarized, as are the related sensing mechanisms.

Journal ArticleDOI
TL;DR: To explore the unidentified determinants of CO2 emissions in G7 countries from 1990 to 2017, this study uses second-generation panel co-integration methodologies and confirms a stable long-run relationship amongCO2 emissions, trade, income, environmental innovation and renewable energy consumption.

Journal ArticleDOI
TL;DR: This review summarizes the existing issues with regard to Li anodes and their underlying reasons and then highlights the recent progress made in the development of high-performance LiAnodes, and proposes the persisting challenges and opportunities toward the exploration of practical Li-metal anodes.
Abstract: Lithium-ion batteries have had a tremendous impact on several sectors of our society; however, the intrinsic limitations of Li-ion chemistry limits their ability to meet the increasing demands of developing more advanced portable electronics, electric vehicles, and grid-scale energy storage systems. Therefore, battery chemistries beyond Li ions are being intensively investigated and need urgent breakthroughs toward commercial applications, wherein the use of metallic Li is one of the most intuitive choices. Despite several decades of oblivion due to safety concerns regarding the growth of Li dendrites, Li-metal anodes are now poised to be revived because of the advances in investigative tools and globally invested efforts. In this review, we first summarize the existing issues with regard to Li anodes and their underlying reasons and then highlight the recent progress made in the development of high-performance Li anodes. Finally, we propose the persisting challenges and opportunities toward the exploration of practical Li-metal anodes.

Journal ArticleDOI
TL;DR: This Review comprehensively surveys the progress in polymer-derived functional HPCMs in terms of how to produce and control their porosities, heteroatom doping effects, and morphologies and their related use and provides perspective on how to predefine the structures of HPC Ms by using polymers to realize their potential applications in the current fields of energy generation/conversion and environmental remediation.
Abstract: Heteroatom-doped porous carbon materials (HPCMs) have found extensive applications in adsorption/separation, organic catalysis, sensing, and energy conversion/storage. The judicious choice of carbon precursors is crucial for the manufacture of HPCMs with specific usages and maximization of their functions. In this regard, polymers as precursors have demonstrated great promise because of their versatile molecular and nanoscale structures, modulatable chemical composition, and rich processing techniques to generate textures that, in combination with proper solid-state chemistry, can be maintained throughout carbonization. This Review comprehensively surveys the progress in polymer-derived functional HPCMs in terms of how to produce and control their porosities, heteroatom doping effects, and morphologies and their related use. First, we summarize and discuss synthetic approaches, including hard and soft templating methods as well as direct synthesis strategies employing polymers to control the pores and/or heteroatoms in HPCMs. Second, we summarize the heteroatom doping effects on the thermal stability, electronic and optical properties, and surface chemistry of HPCMs. Specifically, the heteroatom doping effect, which involves both single-type heteroatom doping and codoping of two or more types of heteroatoms into the carbon network, is discussed. Considering the significance of the morphologies of HPCMs in their application spectrum, potential choices of suitable polymeric precursors and strategies to precisely regulate the morphologies of HPCMs are presented. Finally, we provide our perspective on how to predefine the structures of HPCMs by using polymers to realize their potential applications in the current fields of energy generation/conversion and environmental remediation. We believe that these analyses and deductions are valuable for a systematic understanding of polymer-derived carbon materials and will serve as a source of inspiration for the design of future HPCMs.

Proceedings ArticleDOI
14 Jun 2020
TL;DR: Qibin et al. as mentioned in this paper proposed a strip pooling strategy, which considers a long but narrow kernel, i.e., 1xN or Nx1, to capture long-range contextual information for pixel-wise prediction tasks.
Abstract: Spatial pooling has been proven highly effective to capture long-range contextual information for pixel-wise prediction tasks, such as scene parsing. In this paper, beyond conventional spatial pooling that usually has a regular shape of NxN, we rethink the formulation of spatial pooling by introducing a new pooling strategy, called strip pooling, which considers a long but narrow kernel, i.e., 1xN or Nx1. Based on strip pooling, we further investigate spatial pooling architecture design by 1) introducing a new strip pooling module that enables backbone networks to efficiently model long-range dependencies; 2) presenting a novel building block with diverse spatial pooling as a core; and 3) systematically comparing the performance of the proposed strip pooling and conventional spatial pooling techniques. Both novel pooling-based designs are lightweight and can serve as an efficient plug-and-play modules in existing scene parsing networks. Extensive experiments on Cityscapes and ADE20K benchmarks demonstrate that our simple approach establishes new state-of-the-art results. Code is available at https://github.com/Andrew-Qibin/SPNet.

Posted Content
TL;DR: In this paper, the authors show that layer normalization is crucial to the performance of pre-LN Transformers and remove the warm-up stage for the training of Pre-LNs.
Abstract: The Transformer is widely used in natural language processing tasks. To train a Transformer however, one usually needs a carefully designed learning rate warm-up stage, which is shown to be crucial to the final performance but will slow down the optimization and bring more hyper-parameter tunings. In this paper, we first study theoretically why the learning rate warm-up stage is essential and show that the location of layer normalization matters. Specifically, we prove with mean field theory that at initialization, for the original-designed Post-LN Transformer, which places the layer normalization between the residual blocks, the expected gradients of the parameters near the output layer are large. Therefore, using a large learning rate on those gradients makes the training unstable. The warm-up stage is practically helpful for avoiding this problem. On the other hand, our theory also shows that if the layer normalization is put inside the residual blocks (recently proposed as Pre-LN Transformer), the gradients are well-behaved at initialization. This motivates us to remove the warm-up stage for the training of Pre-LN Transformers. We show in our experiments that Pre-LN Transformers without the warm-up stage can reach comparable results with baselines while requiring significantly less training time and hyper-parameter tuning on a wide range of applications.

Journal ArticleDOI
TL;DR: Environmental pollutants such as PM10, PM2.5, SO2, NO2, and CO have a significant correlation with the COVID-19 epidemic in California, and this study is a useful supplement to encourage regulatory bodies to promote changes in environmental policies as pollution source control can reduce the harmful effects of environmental pollutants.


Journal ArticleDOI
TL;DR: The relationships among the structural and compositional features of the newly synthesized MOF materials and their separation properties and mechanisms are highlighted and the existing challenges and possible research directions related to the further exploration of porous MOFs in this very active field are discussed.
Abstract: The separation and purification of light hydrocarbons (LHs) mixtures is one of the most significantly important but energy demanding processes in the petrochemical industry. As an alternative technology to energy intensive traditional separation methods, such as distillation, absorption, extraction, etc., adsorptive separation using selective solid adsorbents could potentially not only lower energy cost but also offer higher efficiency. The need to develop solid materials for the efficiently selective adsorption of LHs molecules, under mild conditions, is therefore of paramount importance and urgency. Metal-organic frameworks (MOFs), emerging as a relatively new class of porous organic-inorganic hybrid materials, have shown promise for addressing this challenging task due to their unparalleled features. Herein, recent advances of using MOFs as separating agents for the separation and purification of LHs, including the purification of CH4 , and the separations of alkynes/alkenes, alkanes/alkenes, C5 -C6 -C7 normal/isoalkanes, and C8 alkylaromatics, are summarized. The relationships among the structural and compositional features of the newly synthesized MOF materials and their separation properties and mechanisms are highlighted. Finally, the existing challenges and possible research directions related to the further exploration of porous MOFs in this very active field are also discussed.

Journal ArticleDOI
TL;DR: This study concluded that the Chinese university students showed higher anxiety for COVID-19, and the results showed that the mean SAS scores were not correlated with the regions they came from/lived in.
Abstract: COVID-19 had become a pandemic raising concerns of widespread panic and increasing anxiety and stress in individuals all over the world (World Health Organization, 2020a). Lots of countries had closed their schools. As the first country to do so, Chinese colleges and universities were making use of different modes of learning, including online-learning based on different platforms to achieve the goal suggested by Ministry of Education in China, "suspending classes without suspending learning," since middle February. This paper is the first one which aims to investigate the anxiety of Chinese university students after the outbreak of COVID-19 right before the start of new spring term. 3611 university students (female: male = 1.48:1) aged between 18 to 24 from all over China were enrolled to this study from a top university in China. The Self-Rating Anxiety Scale - SAS (Zung, 1971) was used to assess anxiety 2 days before the start of new spring term in middle February. All four-year undergraduate students were included in the study. The mean SAS score was 40.53 (SD = 10.15), significantly higher than the national norm (Mean = 29.78, SD = 10.07, and p ≤ .001), and there were still 557 (15.43%, Mean = 58.75, and SD = 8.9) students met the cutoff of 50 and were screened positive. Comparisons among sexes, grades and majors were also conducted. Significant differences were found between all males and all female (p ≤ .001), and between all students majoring arts and sciences in the anxiety sample (n = 557, p = 0.05). The results also showed that the mean SAS scores were not correlated with the regions they came from/lived in. This study concluded that the Chinese university students showed higher anxiety for COVID-19.

ComponentDOI
10 Mar 2020-bioRxiv
TL;DR: The results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.
Abstract: SUMMARY A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1-4. Currently there is no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these inhibit Mpro with IC50 values ranging from 0.67 to 21.4 μM. Ebselen also exhibited strong antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.

Journal ArticleDOI
Qiu Zhang1, Yilin Ma1, Yong Lu1, Lin Li1, Fang Wan1, Kai Zhang1, Jun Chen1 
TL;DR: This work significantly provides an effective strategy to propel low-temperature aqueous batteries via tuning the electrolyte structure and widens the application range of temperature adaptation of aQueous batteries.
Abstract: Rechargeable aqueous batteries are an up-and-coming system for potential large-scale energy storage due to their high safety and low cost. However, the freeze of aqueous electrolyte limits the low-temperature operation of such batteries. Here, we report the breakage of original hydrogen-bond network in ZnCl2 solution by modulating electrolyte structure, and thus suppressing the freeze of water and depressing the solid-liquid transition temperature of the aqueous electrolyte from 0 to –114 °C. This ZnCl2-based low-temperature electrolyte renders polyaniline||Zn batteries available to operate in an ultra-wide temperature range from –90 to +60 °C, which covers the earth surface temperature in record. Such polyaniline||Zn batteries are robust at –70 °C (84.9 mA h g−1) and stable during over 2000 cycles with ~100% capacity retention. This work significantly provides an effective strategy to propel low-temperature aqueous batteries via tuning the electrolyte structure and widens the application range of temperature adaptation of aqueous batteries. Rechargeable aqueous batteries are promising for potential large-scale energy storage due to their high safety and low cost. Here the authors analyse a zinc chloride based low-temperature electrolyte for improving practicability of the aqueous batteries.

Journal ArticleDOI
Ting Jin1, Huangxu Li1, Kunjie Zhu1, Peng-Fei Wang1, Pei Liu1, Lifang Jiao1 
TL;DR: This review summarizes the recent progress of polyanion-type materials for SIBs, which include phosphates, fluorophosphate, pyrophosphates, mixed phosphate, sulfates, and silicates, and discusses the remaining challenges and corresponding strategies for polyanionic materials.
Abstract: Room-temperature sodium-ion batteries (SIBs) are regarded as promising candidates for smart grids and large-scale energy storage systems (EESs) due to their significant benefits of abundant and low-cost sodium resource. Among the previously reported cathode materials for SIBs, layered transition-metal oxides and polyanion-type materials are considered to be the most attractive options. Although many layered transition-metal oxides can provide high capacity due to their small molecular weight, their further application is hindered by low output voltage (mostly lower than 3.5 V), irreversible phase transition as well as storage instability. Comparatively, polyanion-type materials exhibit higher operating potentials due to the inductive effect of polyanion groups. Their robust 3D framework significantly decreases the structural variations during sodium ion de/intercalation. Moreover, the effect of strong X-O (X = S, P, Si, etc.) covalent bonds can effectively inhibit oxygen evolution. These advantages contribute to the superior cycle stability and high safety of polyanion-type materials. However, low electronic conductivity and limited capacity still restrict their further application. This review summarizes the recent progress of polyanion-type materials for SIBs, which include phosphates, fluorophosphates, pyrophosphates, mixed phosphates, sulfates, and silicates. We also discuss the remaining challenges and corresponding strategies for polyanion-type materials. We hope this review can provide some insights into the development of polyanionic materials.

Journal ArticleDOI
TL;DR: The X-ray crystal structure of SARS-CoV-2 with inhibitor carmofur reveals the mechanism of action of this compound and opens the way to develop more potent drugs.
Abstract: The antineoplastic drug carmofur is shown to inhibit the SARS-CoV-2 main protease (Mpro). Here, the X-ray crystal structure of Mpro in complex with carmofur reveals that the carbonyl reactive group of carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 μM) and is a promising lead compound to develop new antiviral treatment for COVID-19.

Journal ArticleDOI
30 Apr 2020-Science
TL;DR: A gelatin-based ionic thermoelectric device that uses alkali salts and an iron-based redox couple to generate a large thermopower, capable of generating useful amounts of energy from body heat, and shows promise for environmental heat-to-electric energy conversion using ions as energy carriers.
Abstract: Harvesting heat from the environment into electricity has the potential to power Internet-of-things (IoT) sensors, freeing them from cables or batteries and thus making them especially useful for wearable devices. We demonstrate a giant positive thermopower of 17.0 millivolts per degree Kelvin in a flexible, quasi-solid-state, ionic thermoelectric material using synergistic thermodiffusion and thermogalvanic effects. The ionic thermoelectric material is a gelatin matrix modulated with ion providers (KCl, NaCl, and KNO3) for thermodiffusion effect and a redox couple [Fe(CN)64–/Fe(CN)63–] for thermogalvanic effect. A proof-of-concept wearable device consisting of 25 unipolar elements generated more than 2 volts and a peak power of 5 microwatts using body heat. This ionic gelatin shows promise for environmental heat-to-electric energy conversion using ions as energy carriers.

Journal ArticleDOI
TL;DR: This paper reviews and synthesizes the current state of knowledge on the acidity of atmospheric condensed phases, specifically particles and cloud droplets, including recommendations for estimating acidity and pH, standard nomenclature, a synthesis of current pH estimates based on observations, and new model calculations on the local and global scale.
Abstract: . Acidity, defined as pH, is a central component of aqueous chemistry. In the atmosphere, the acidity of condensed phases (aerosol particles, cloud water, and fog droplets) governs the phase partitioning of semivolatile gases such as HNO3 , NH3 , HCl, and organic acids and bases as well as chemical reaction rates. It has implications for the atmospheric lifetime of pollutants, deposition, and human health. Despite its fundamental role in atmospheric processes, only recently has this field seen a growth in the number of studies on particle acidity. Even with this growth, many fine-particle pH estimates must be based on thermodynamic model calculations since no operational techniques exist for direct measurements. Current information indicates acidic fine particles are ubiquitous, but observationally constrained pH estimates are limited in spatial and temporal coverage. Clouds and fogs are also generally acidic, but to a lesser degree than particles, and have a range of pH that is quite sensitive to anthropogenic emissions of sulfur and nitrogen oxides, as well as ambient ammonia. Historical measurements indicate that cloud and fog droplet pH has changed in recent decades in response to controls on anthropogenic emissions, while the limited trend data for aerosol particles indicate acidity may be relatively constant due to the semivolatile nature of the key acids and bases and buffering in particles. This paper reviews and synthesizes the current state of knowledge on the acidity of atmospheric condensed phases, specifically particles and cloud droplets. It includes recommendations for estimating acidity and pH, standard nomenclature, a synthesis of current pH estimates based on observations, and new model calculations on the local and global scale.

Journal ArticleDOI
M. Ablikim, M. N. Achasov1, M. N. Achasov2, Patrik Adlarson3  +500 moreInstitutions (73)
Abstract: There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESIII and B factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related X(1835) meson state at BESIII, as well as the threshold measurements of charm mesons and charm baryons. We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESIII during the remaining operation period of BEPCII. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCII to higher luminosity.