Transition Metal Functionalized C30N12S6 as High-Performance Trifunctional Catalysts with Integrated Descriptors toward Hydrogen Evolution, Oxygen Evolution, and Oxygen Reduction Reactions: A Case of High-Throughput First-Principles Screening within the Framework of TM-N2@C30N10S6.

In energy conversion and storage technologies, the design of highly efficient trifunctional electrocatalysts integrating with the high hydrogen evolution reaction (HER) and oxygen evolution/reduction reaction (OER/ORR) activities is highly desirable. Herein, utilizing first-principles computations, a novel periodically ordered macropore C30N12S6 monolayer was proposed, and the stability analysis attests to its good stability. Single transition metal (TM) atom anchored onto this newly proposed C30N12S6 monolayer to form single-atom catalysts, as achieved by TM-N2@C30N10S6, among which the Co-N2@C30N10S6 is the most promising multifunctional catalyst toward HER/OER/ORR with low overpotential of 0.01/0.59/0.3 V; meanwhile, the Rh-N2@C30N10S6 can be used as a bifunctional OER/ORR catalyst with low overpotential of 0.37/0.44 V, overmatching the landmark Pt (111) and IrO2/RuO2 catalysts. Particularly, the TM-d orbital in TM@CNS is remarkably hybridized with the O-p orbital of oxygenated intermediates, so that the lone electrons initially located at the antibonding orbital pair up and fill the downward bonding orbital, allowing OH* to be suitably adsorbed on TM@CNS, enhancing the catalytic performance. The relevant attributes, such as good stabilities and metallic features, ensured their applications in ambient conditions. Moreover, multilevel descriptors were constructed to clarify the origin of activity on TM@CNS, such as ΔGOH* (Gibbs free energy of OH*), εd (d-band center), COHP (crystal orbital Hamilton population), Nd/Nd + s (number of d/d + s electrons) and φ (descriptor), among which the filling of outer d-electrons of TM atom significantly affects the value of ΔGOH* that can determine the overpotential and, thus, become a key descriptor.

Surface Confinement of Finite-Size Water Droplets for SO3 Hydrolysis Reaction Revealed by Molecular Dynamics Simulations Based on a Machine Learning Force Field.

As an important source for sulfuric acid in the atmosphere, hydrolysis of sulfur trioxide (SO3) takes place with water clusters of sizes from several molecules to several nanometers, resulting in various final products, including neutral (H2SO4)-(H2O) clusters and ionic (HSO4)--(H3O)+ clusters. The diverse products may be due to the ability of proton transfer and the formation of hydrated ions for water cluster of finite sizes, especially the sub-micrometer ones. However, the detailed molecular-level mechanism is still unclear due to the lack of available characterization and simulations tools. Here, we developed a quantum chemistry-level machine learning (ML) model to simulate the hydrolysis of SO3 with water clusters of sizes up to nanometers. The simulation results demonstrate diverse reaction paths taking place between SO3 and water clusters of different sizes. Generally, neutral (H2SO4)-(H2O) clusters are preferred by water clusters of ultra-small size, and a loop structure-mediated mechanism with SO3(H2O)n≤4 structures and a non-loop structure-mediated mechanism with structure relaxation are observed. As the water cluster size increases to (H2O)8, a (HSO4)--(H3O)+ ion-pair product emerges; and the Eigen-Zundel ion conversion-like proton transfer mechanism takes place and stabilizes the ion pairs. As the water cluster sizes further increase beyond several nanometers ((H2O)n≥32), the (SO4)2-[(H3O)+]2 ion-pair product appears. The reason could be that the surface of these water clusters is large enough to screen Coulomb repulsion between two tri-coordinated ion-pair complexes. These findings would provide new perspectives for understanding SO3 hydrolysis in the real atmosphere and sulfuric acid chemistry in atmospheric aerosols.

Molecular vibrational spectral simulation connects theoretical cluster structure identification and vibrational spectral evidence.

Structure identification of molecular clusters has long been a fundamental and challenging issue for cluster science. The traditional theoretical optimization on the potential energy surface heavily depends on the levels of theory and sometimes diverse identifications were reported. A solution to these disputations is to reinspect the theoretical results with the experimental data such as vibrational predissociation spectra with high sensitivity to the molecular cluster structures. Herein, the combination of global low-lying structure search and vibrational predissociation spectral simulation is proposed as an accurate and reliable approach for cluster structure identification, by which the assignments can be validated using experimental measurements. The qualitative agreement between simulated and measured vibrational spectra lends solid experimental evidence to the assignment of the cluster structures. Taking NH4+(H2O)n (n = 2-4) as an example, we have unambiguously identified their structures and directly demonstrated the coexistence of two NH4+(H2O)4 isomers (with 3 and 4 water molecules directly linked to NH4+, respectively), which were debatable in previous studies. The developed methods would pave the way to the structure determination of the molecular clusters.

Sulfuric acid-dimethylamine particle formation enhanced by functional organic acids: an integrated experimental and theoretical study.

Atmospheric new particle formation (NPF), which has been observed globally in clean and polluted environments, is an important source of boundary-layer aerosol particles and cloud condensation nuclei, but the fundamental mechanisms leading to multi-component aerosol formation have not been well understood. Here, we use experiments and quantum chemical calculations to better understand the involvement of carboxylic acids in initial NPF from gas phase mixtures of carboxylic acid, sulfuric acid (SA), dimethylamine, and water. A turbulent flow tube coupled to an ultrafine condensation particle counter with particle size magnifier has been set up to measure NPF. Experimental results show that pyruvic acid (PA), succinic acid (SUA), and malic acid (MA) can enhance sulfuric acid-dimethylamine nucleation in the order PA < SUA < MA with a greater enhancement observed at lower SA concentrations. Computational results indicate that the carboxylic and hydroxyl groups are related to the enhancement. This experiment-theory study shows the formation of multi-component aerosol particles and the role of the organic functional group, which may aid in understanding the role of organics in aerosol nucleation and growth in polluted areas, and help to choose organic molecules of specific structures for simulation.

Exploring TCGA database for identification of potential prognostic genes in stomach adenocarcinoma.

BACKGROUND: Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer in the world and ranks third among cancer-related deaths worldwide. The tumour microenvironment (TME) plays an important role in tumorigenesis, development, and metastasis. Hence, we calculated the immune and stromal scores to find the potential prognosis-related genes in STAD using bioinformatics analysis. METHODS: The ESTIMATE algorithm was used to calculate the immune/stromal scores of the STAD samples. Functional enrichment analysis, protein-protein interaction (PPI) network analysis, and overall survival analysis were then performed on differential genes. And we validated these genes using data from the Gene Expression Omnibus database. Finally, we used the Human Protein Atlas (HPA) databases to verify these genes at the protein levels by IHC. RESULTS: Data analysis revealed correlation between stromal/immune scores and the TNM staging system. The top 10 core genes extracted from the PPI network, and primarily involved in immune responses, extracellular matrix, and cell adhesion. There are 31 genes have been validated with poor prognosis and 16 genes were upregulated in tumour tissues compared with normal tissues at the protein level. CONCLUSIONS: In summary, we identified genes associated with the tumour microenvironment with prognostic implications in STAD, which may become potential therapeutic markers leading to better clinical outcomes.

DECREASE IN ACROMEGALY-ASSOCIATED THYROID ENLARGEMENT AFTER NORMALIZATION OF IGF-1 LEVELS: A PROSPECTIVE OBSERVATION AND IN VITRO STUDY.

Objective: Goiter occurs at high frequency in acromegaly patients. Whether normalization of insulin-like growth factor 1 (IGF-1) levels could decrease goiter and thyroid volume remains unclear. Methods: Thyroid hormone levels and ultrasound measurements were assessed in 101 acromegaly patients, compared with 108 patients with nonfunctioning pituitary adenoma (NFPA) and 55 healthy controls. Thirty-four acromegaly patients underwent repeat evaluation 1 year post-transsphenoidal surgery. The effect of IGF-1 on thyroid cell proliferation, cell cycle, and apoptosis was evaluated in vitro. Results: Acromegaly patients showed larger thyroid volume than those with NFPAs (18.32 mL vs. 9.91 mL; P<.001) and healthy controls (18.32 mL vs. 9.63 mL; P<.001). Duration of acromegaly was shown to be independently associated with thyroid volume enlargement (B = 0.259; 95% confidence interval, 0.162 to 0.357) in multivariate analysis. At follow-up, the median thyroid volume decreased from 22.74 to 17.87 mL in the cured group (n = 20; P = .003), but the number of nodular goiters showed no significant change. Serum free thyroxine levels decreased from 13.76 to 10.08 pmol/L in the cured group (P = .006) but increased from 9.28 to 12.09 pmol/L in the active group (P = .013). Change in thyroid volume was significantly correlated with IGF-1 level (r = 0.37; P = .029). In vitro, IGF-1 time- and dose-dependently promoted proliferation and secretory function of thyroid cells by enhancing cell cycle shift from the G1/S to G2/M phase and suppressing apoptosis. Conclusion: Acromegaly-associated thyroid volume increase, but not nodular goiter, could be reversed in cured acromegaly. IGF-1 time- and dose-dependently promoted the proliferation and secretory function of thyroid cells. Abbreviations: CCK-8 = Cell Counting Kit-8; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; IGF-1 = insulin-like growth factor 1; MRI = magnetic resonance imaging; NFPA = nonfunctioning pituitary adenoma; qRT-PCR = quantitative real-time-polymerase chain reaction; TSH = thyroid-stimulating hormone.

MiR-1299 promotes the synthesis and secretion of prolactin by inhibiting FOXO1 expression in drug-resistant prolactinomas.

Prolactinoma is a clinically common intracranial tumor. When serum prolactin levels are not controlled despite administration of a dopamine agonist, the condition is referred to as drug-resistant prolactinoma. The mechanism underlying persistent prolactin secretion in drug-resistant prolactinoma remains unclear. MicroRNAs play an important role in tumorigenesis and development as well as chemotherapeutic resistance. This study was conducted to investigate the mechanism by which miRNA regulates prolactin secretion in drug-resistant prolactinoma. We first found that miR-1299 was elevated in drug-resistant prolactinoma and inhibited FOXO1 in a targeted manner through miRNA sequencing and luciferase assays. We then confirmed that FOXO1 binds to the promoter of the prolactin gene to inhibit its expression through chromatin immunoprecipitation-quantitative PCR and cytological experiments. Finally, inhibition or overexpression of miR-1299 in primary tumor cells confirmed that drug-resistant prolactinoma promoted prolactin secretion by promoting miR-1299 expression and reducing intracellular FOXO1. These results indicate that FOXO1 and miR-1299 are potential therapeutic targets for drug-resistant prolactinoma as well as other pituitary diseases.

Enhancement of Atmospheric Nucleation by Highly Oxygenated Organic Molecules: A Density Functional Theory Study.

New particle formation (NPF) by gas-particle conversion is the main source of atmospheric aerosols. Highly oxygenated organic molecules (HOMs) and sulfuric acid (SA) are important NPF participants. 2-Methylglyceric acid (MGA), a kind of HOMs, is a tracer of isoprene-derived secondary organic aerosols. The nucleation mechanisms of MGA with SA were studied using density functional theory and atmospheric cluster dynamics simulation in this study, along with that of MGA with methanesulfonic acid (MSA) as a comparison. Our theoretical works indicate that the (MGA)(SA) and (MGA)(MSA) clusters are the most stable ones in the (MGA) i(SA) j ( i = 1-2, j = 1-2) and (MGA) i(MSA) j ( i = 1-2, j = 1-2) clusters, respectively. Both the formation rates of (MGA)(SA) and (MGA)(MSA) clusters are quite large and could have significant contributions to NPF. The results imply that the homomolecular nucleation of MGA is unlikely to occur in the atmosphere, and MGA and SA can effectively contribute to heteromolecular nucleation mainly in the form of heterodimers. MSA exhibits properties similar to SA in its ability to form clusters with MGA but is slightly weaker than SA.

MicroRNAs and Target Genes in Pituitary Adenomas.

Pituitary adenomas account for the top three primary intracranial tumors in terms of total incidence rates. The clinical symptoms presented by the disease are often characterized by a series of systemic endocrine disorders, severe occupational lesions, and even some malignant features, and therefore early diagnosis and predicting recurrence would be instructive for clinical treatment of pituitary adenomas. An increasing number of specific microRNA (miRNA) expression signatures have been identified in pituitary, and miRNAs are related with the pituitary tumorigenesis, dysfunction, neurodegeneration, and metastatic non-functioning pituitary carcinoma. Here, this paper reviews the effects of aberrant miRNA expression in human pituitary adenomas and summarizes some corresponding target genes and biological significance over the last 7 years (2010-2017).

Hydration of 3-hydroxy-4,4-dimethylglutaric acid with dimethylamine complex and its atmospheric implications.

Atmospheric aerosols have a tremendous influence on visibility, climate, and human health. New particle formation (NPF) is a crucial source of atmospheric aerosols. At present, certain field observations and experiments have discovered the presence of 3-hydroxy-4,4-dimethylglutaric acid (HDMGA), which may participate in NPF events. However, the nucleation mechanism of HDMGA has not been clearly understood. In addition, dimethylamine (DMA) is an important precursor of nucleation. The nucleation mechanism involving HDMGA and DMA has not been studied. In this study, the most stable structures of (HDMGA)(H2O)n (n = 0-3) and (HDMGA)(DMA)(H2O)n (n = 0-3) were obtained by using M06-2X coupled with the 6-311++G(3df,3pd) basis set. The α-carboxyl group is directly attached to the amino group in all the most stable configurations. Proton transfer enhances the strength of a hydrogen bond, as well as promotes the generation of a global minimum structure. Temperature has a considerable influence on the distribution of isomers for (HDMGA)(DMA)(H2O)3 as compared to the other investigated clusters. The Gibbs free energy values reveal that most of the clusters can exist in NPF, except for (HDMGA)(H2O)1. The process of adding a cluster of (H2O)n more likely occurs in the atmosphere than gradually adding a single water molecule.

Lysosome Inhibitors Enhance the Chemotherapeutic Activity of Doxorubicin in HepG2 Cells.

The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis. Further studies reveal that bafilomycin A1 and chloroquine promote lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin. Our findings suggest that bafilomycin A1 and chloroquine potentiate the anticancer effect of doxorubicin in hepatic cancer cells and that supplementation of conventional chemotherapy with lysosome inhibitors may provide a more efficient anticancer therapy.

Bidirectional Interaction of Alanine with Sulfuric Acid in the Presence of Water and the Atmospheric Implication.

Amino acids are recognized as important components of atmospheric aerosols, which impact on the Earth's climate directly and indirectly. However, much remains unknown about the initial events of nucleation. In this work, the interaction of alanine [NH2CH(CH3)COOH or Ala], one of the most abundant amino acids in the atmosphere, with sulfuric acid (SA) and water (W) has been investigated at the M06-2X/6-311++G(3df, 3pd) level of theory. We have studied thermodynamics of the hydrated (Ala)(SA) core system with up to four water molecules. We found that Ala, with one amino group and one carboxyl group, can interact with H2SO4 and H2O in two directions and that it has a high cluster stabilizing effect similar to that of ammonia, which is one of the key nucleation precursor. The corresponding Gibbs free energies of the (Ala)(SA)(W)n (n = 0-4) clusters formation at 298.15 K predicted that Ala can contribute to the stabilization of small binary clusters. Our results showed that the hydrate distribution is temperature-dependent and that a higher humidity and temperature can contribute to the formation of hydrated clusters.

Stability of Hydrated Methylamine: Structural Characteristics and H2N···H-O Hydrogen Bonds.

Methylamine is the simplest aliphatic amine found in human urine, blood, and tissues. It is thought to play a significant part in central nervous system disturbances observed during renal and hepatic disease. In this work we have investigated the methylamine hydration clusters using a basin hopping (BH) algorithm with the density functional theory (DFT). The results presented herein yield a detailed understanding of the structure and stability for a system consisting of one methylamine molecule and up to seven waters: the most stable geometries arise from a fusion of tetramer or pentamer rings; by the geometrical parameters and topological parameters analysis, the strengths of the H2N···H-O hydrogen bonds of the global minima increase as the sizes of clusters increase, except for n = 5 where there is a slight fluctuation. This work may shed light on the form mechanism of methylamine existing in organisms and the hydration structures of larger molecules containing amino functional groups and their interaction with the water molecules nearby.

Sensitive detection of microcystin-LR by using a label-free electrochemical immunosensor based on Au nanoparticles/silicon template/methylene blue nanocomposite.

A label-free electrochemical immunosensor, based on a gold nanoparticles (Au NPs)/silicon template/methylene blue (MB)/chitosan (CHIT) nanocomposite-modified electrode, was fabricated for the ultrasensitive detection of microcystin-LR (MC-LR). The nanocomposite film showed high binding affinity to the antibodies of MC-LR because gold nanoparticles have large surface area and good biocompatibility which can immobilize large amount of antibody through ionic interactions and other interactions between AuNPs and mercapto or primary amine groups of antibodies with high stability and bioactivity. MB was used as redox indicator due to its good electrochemical behavior in conductive substrate. This hybrid membrane was evaluated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) to determine its electrochemical properties in immunosensor application. A decrease in DPV responses was observed with increasing concentrations of MC-LR in standard and real samples due to the formation of immuno-complexes between MC-LR and anti-MC-LR antibodies which hindered the electron charge transfer at the electrode-electrolyte interface. At optimal conditions, this immunosensor could detect MC-LR in a linear range from 0.5 ng/mL to 25 microg/mL with a low detection limit of 0.1 ng/mL at 3 sigma. Moreover, the prepared immunosensor was applied for the analysis of MC-LR in water samples with satisfactory results. The proposed method showed high selectivity, acceptable reproducibility, stability and reliability.

Ginkgolide B promotes spontaneous recovery and enhances endogenous netrin-1 after neonatal hypoxic-ischemic brain damage.

OBJECTIVES: Perinatal hypoxic-ischemic encephalopathy (HIE) is a condition that can lead to long-term cognitive, motor, and behavioral impairments in newborns. Although brain hypothermia therapy is currently the standard treatment for HIE, it does not provide complete neuroprotection. As a result, there is a need to explore additional therapies to enhance treatment outcomes. This study aims to investigate the potential role of Ginkgolide B (GB) in promoting neuroplasticity and facilitating spontaneous recovery after HIE. METHODS: In this study, we employed a neonatal rat model of HIE to investigate the effects of GB on spontaneous recovery. GB treatment was initiated 24 h after hypoxia and administered continuously for a duration of 14 days. We evaluated several outcome measures after the treatment period, including spontaneous behavioral recovery and brain repair. Additionally, we quantified the levels of netrin-1 in both plasma and the peri-ischemic zone after the occurrence of HIE. RESULTS: We found that GB treatment significantly facilitated spontaneous behavioral recovery in the HIE pups. Furthermore, cognitive function was restored, and brain tissue repair had a noticeable acceleration. We observed increased cell proliferation in the subventricular, stratum, and subgranular zones. Of particular interest, we observed elevated levels of netrin-1 in both plasma and the ischemic penumbra following GB treatment. CONCLUSION: Our findings suggest that GB promotes neuroplasticity and enhances spontaneous recovery in newborns affected by HIE. The observed upregulation of netrin-1 may be crucial in mediating these effects. These results highlight the promising potential of GB as a post-HIE therapy, particularly in enhancing spontaneous recovery and improving long-term outcomes.

PDTC attenuate LPS-induced kidney injury in systemic lupus erythematosus-prone MRL/lpr mice.

Lipopolysaccharide (LPS) from bacteria can accelerate and exacerbate lupus nephritis (LN) and induce infiltrating inflammatory cells in kidney in animal models. Pyrrolidine dithiocarbamate (PDTC) is known to exert anti-inflammatory effects. Monocyte chemoattractant protein-1(MCP-1) is upregulated by various stimuli, including LPS, high glucose, and hyperosmolality. However, the molecular mechanisms of transcriptional regulation of the MCP-1 protein expression with LPS are poorly understood. Expression of MCP-1 was examined by western blot and enzyme-linked immunosorbent assay, respectively. The activity of nuclear factor (NF)-kappaB was measured by western blot. These mice have uncontrolled proliferation of T cells, an impaired response to T cell mitogen and produce autoantibodies against nuclear antigens, including DNA. We found that after LPS treatment for 14 weeks, LPS increased MCP-1 protein expression in kidney, which was significantly suppressed by antioxidant PDTC. The expression of NF-κB, pERK, pJNK and MCP-1 were increased, pp38 expression was decreased significantly, concomitantly with sera anti-dsDNA, MCP-1 and the acceleration of severity of autoimmune kidney injury. LPS induce markedly neutrophil infiltration in the glomerulus, especially around the mesangial region. PDTC reduced the number of infiltrating inflammatory cells and severity of kidney injury via inhibiting NF-κB and p38 MAPK activity. They also markedly prevented LPS-induced pJNK and MCP-1. Therefore, MCP-1 may be responsible for the recruitment and activation of leukocytes in diseased kidneys in female MRL/lpr mice. In this study, the long-term administration of PDTC had impacts on the prevention of end-stage organ damage induced by LPS treated. We demonstrated that PDTC inhibited LPS-induced monocyte migration and attenuated LPS-induced p38 MAPK activation. Based on these data we infer that PDTC inhibits LPS-induced MCP-1 expression, secretion and function through inhibition of NF-κB and p38 MAPK activity. Our study suggests that MAPK is an important therapeutic target of monocyte recruitment and accumulation within the glomerulus in inflammatory renal disease. These results suggest that PDTC protects against kidney inflammation of SLE at least in part via NF-κB and MAPK signaling pathways induction, and that inhibitory action on anti-dsDNA may be associated with the protective mechanism of PDTC. In summary, PDTC pretreatment attenuates LPS-induced kidney injury in female MRL/lpr mice through regulating NF-κB and MAPK signaling pathways. Our results indicate that LPS induces MCP-1 mainly through activating NF-κB and its downstream MAPK, and that such effect was inhibited by PDTC, suggesting the efficacy of PDTC in preventing kidney fibrosis in lupus-prone mice. Therefore, appropriate inhibition of NF-κB activation may attenuate the kidney injury in lupus-prone mice.

Lewis Acid-Base Adducts for Efficient and Stable Cesium-Based Lead Iodide-Rich Perovskite Solar Cells.

All-inorganic cesium-lead-iodide (CsPbI3 Br3- x (2 < x < 3)) perovskite presents preeminent photovoltaic performance and chemical stability. Unfortunately, this kind of material suffers from phase transition to a nonperovskite phase under oxidative chemical stresses. Herein, the introduction of a low concentration of Lewis acid-base adducts (LABAs) is reported to synergistically reduce defect density, optimize interfacial energy alignment, and improve device stability of CsPbI2.75 Br0.24 Cl0.01 (CsPbTh3 ) solar cells. Both theoretical simulations and experimental measurements reveal that the noncoordinating anions, PF6 - , as a Lewis base can more effectively bind with undercoordinated Pb2+ to passivate iodide vacancy defects than the BF4 - and absorbed I- , and thus the point defects are well suppressed. In addition, N-propyl-methyl piperidinium (NPMP+ ) is selected to assemble with PF6 - in CsPbTh3 film. The NPMP+ can regulate the crystal growth and finally homogenize the grain size and decrease the trap density. Consequently, the LABAs strategy can improve the power conversion efficiency of CsPbTh3 solar cells to 19.02% under 1-sun illumination (100 mW cm-2 ). Fortunately, the NPMP+ and PF6 - -treated CsPbTh3 film shows great phase stability after storage in ambient air for 250 days, and the power conversion efficiency of corresponding solar cells is almost 76% of the initial value after 60 days aging under ambient conditions.

Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease.

The current COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enormous threat to public health. The SARS-CoV-2 3C-like protease (3CLpro), which is critical for viral replication and transcription, has been recognized as an ideal drug target. Herein, it is identified that three herbal compounds, Salvianolic acid A (SAA), (-)-Epigallocatechin gallate (EGCG), and Oridonin, directly inhibit the activity of SARS-CoV-2 3CLpro. Further, blocking SARS-CoV-2 infectivity by Oridonin is confirmed in cell-based experiments. By solving the crystal structure of 3CLpro in complex with Oridonin and comparing it to that of other ligands with 3CLpro, it is identified that Oridonin binds at the 3CLpro catalytic site by forming a C-S covalent bond, which is confirmed by mass spectrometry and kinetic study, blocking substrate binding through a nonpeptidomimetic covalent binding mode. Thus, Oridonin is a novel candidate to develop a new antiviral treatment for COVID-19.

Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease.

Oridonin Inhibits SARS-CoV-2 Oridonin, a natural product extracted from Rabdosia rubescens, possesses a wide range of pharmacological properties, including anti-inflammatory, anti-cancer, anti-microbial, neuroprotection, immunoregulation, etc. In article number 2100124, Baisen Zhong, Litao Sun, and co-workers demonstrate that Oridonin targets the SARS-CoV-2 3CL protease by covalently binding to cysteine145 in its active pocket to exert an anti-SARS-CoV-2 effect, which provides a novel candidate for the treatment of COVID-19.