Biology subjects

Ding, L.

Publications and source records attributed to Ding, L..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

Early microbial intervention reduces diarrhea while improves later milk production in newborn calves

The rumen of neonatal calves is not well-developed and exhibits limited functionality. Therefore, the establishment of intestinal microbiota may play an instrumental role in their health and performance, but it has been rarely explored. Thus, we aim to explore the temporal colonization of the gut microbiome and the potential benefits of early microbial intervention in newborn calves. We followed up on the temporal dynamics of the gut microbiome and plasma metabolome in 36 newborn calves during the first two months of life and established their relationships with their health status and performance. We also evaluated whether microbiota transplantation (MT) could influence their phenotypes by modulating metabolism and its impact on later milk production performance.We showed that the composition and ecological interactions of the gut microbiome are likely to reach maturity one month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion, antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. The data from the study may help develop strategies to manipulate the gut microbiota during early life, which may be significantly relevant to the health and production of newborn calves. HIGHLIGHTSO_LIThe gut microbial composition and ecological interaction in newborn calves reach maturity one month after birth C_LIO_LITemporal shifts in the gut microbiome of newborn calves are associated with phenotypic changes, including growth, digestion, and antioxidative capacity C_LIO_LIEarly microbial intervention in newborn calves reduces diarrhea while improving later milk production C_LIO_LIThe gut microbial impact on newborn calves is mediated by plasma metabolites C_LI

microbiology↗

bioRxiv2023

Microsatellites used in forensics are located in regions unusually rich in trait-associated variants

The 20 short tandem repeat (STR) markers of the combined DNA index system (CODIS) are the basis of the vast majority of forensic genetics in the United States. One argument for permissive rules about the collection of CODIS genotypes is that the CODIS markers are thought to contain information relevant to identification only (such as a human fingerprint would), with little information about ancestry or traits. However, in the past 20 years, a quickly growing field has identified hundreds of thousands of genotype-trait associations. Here we conduct a survey of the landscape of such associations surrounding the CODIS loci as compared with non-CODIS STRs. We find that the regions around the CODIS markers are enriched for both known pathogenic variants (>90th percentile) and for SNPs identified as trait-associated in genome-wide association studies (GWAS) ([≥]95th percentile in 10kb and 100kb flanking regions), compared with other random sets of autosomal tetranucleotide-repeat STRs. Although it is not obvious how much phenotypic information CODIS would need to convey to strain the "DNA fingerprint" analogy, the CODIS markers, considered as a set, are in regions unusually dense with variants with known phenotypic associations.

genetics↗

bioRxiv2023

KIF16B mediates anterograde transport and modulates lysosomal degradation of the HIV-1 envelope glycoprotein

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) is incorporated into virions at the site of particle assembly on the plasma membrane (PM). The route taken by Env to reach the site of assembly and particle incorporation remains incompletely understood. Following initial delivery to the PM through the secretory pathway, Env is rapidly endocytosed, suggesting that recycling is required for particle incorporation. Endosomes marked by the small GTPase Rab14 have been previously shown to play a role in Env trafficking. Here we examined the role of KIF16B, the molecular motor protein that directs outward movement of Rab14-dependent cargo, in Env trafficking. Env colocalized extensively with KIF16B+ endosomes at the cellular periphery, while expression of a motor-deficient mutant of KIF16B redistributed Env to a perinuclear location. The half-life of Env labeled at the cell surface was markedly reduced in the absence of KIF16B, while a normal half-life was restored through inhibition of lysosomal degradation. In the absence of KIF16B, Env expression on the surface of cells was reduced, leading to a reduction in Env incorporation into particles and a corresponding reduction in particle infectivity. HIV-1 replication in KIF16B knockout cells was substantially reduced as compared to wildtype cells. These results indicate that KIF16B regulates an outward sorting step involved in Env trafficking, thereby limiting lysosomal degradation and enhancing particle incorporation. IMPORTANCEThe HIV-1 envelope glycoprotein is an essential component of HIV-1 particles. The cellular pathways that contribute to incorporation of envelope into particles are not fully understood. Here we identify KIF16B, a motor protein that directs movement from internal compartments toward the plasma membrane, as a host factor that prevents envelope degradation and enhances particle incorporation. This is the first host motor protein identified that contributes to HIV-1 envelope incorporation and replication.

microbiology↗

bioRxiv2023

scMINER: a mutual information-based framework for identifying hidden drivers from single-cell omics data

The sparse nature of single-cell omics data makes it challenging to dissect the wiring and rewiring of the transcriptional and signaling drivers that regulate cellular states. Many of the drivers, referred to as "hidden drivers", are difficult to identify via conventional expression analysis due to low expression and inconsistency between RNA and protein activity caused by post-translational and other modifications. To address this issue, we developed scMINER, a mutual information (MI)-based computational framework for unsupervised clustering analysis and cell-type specific inference of intracellular networks, hidden drivers and network rewiring from single-cell RNA-seq data. We designed scMINER to capture nonlinear cell-cell and gene-gene relationships and infer driver activities. Systematic benchmarking showed that scMINER outperforms popular single-cell clustering algorithms, especially in distinguishing similar cell types. With respect to network inference, scMINER does not rely on the binding motifs which are available for a limited set of transcription factors, therefore scMINER can provide quantitative activity assessment for more than 6,000 transcription and signaling drivers from a scRNA-seq experiment. As demonstrations, we used scMINER to expose hidden transcription and signaling drivers and dissect their regulon rewiring in immune cell heterogeneity, lineage differentiation, and tissue specification. Overall, activity-based scMINER is a widely applicable, highly accurate, reproducible and scalable method for inferring cellular transcriptional and signaling networks in each cell state from scRNA-seq data. The scMINER software is publicly accessible via: https://github.com/jyyulab/scMINER.

systems biology↗

bioRxiv2023

TOBF1 modulates mouse embryonic stem cell fate through co-transcriptional regulation of alternative splicing

Embryonic stem (ES) cells retain the ability to undergo lineage-specific differentiation that can eventually give rise to different cell types that constitute an organism. Although stem cell specific biological networks of transcription factors and epigenetic modifiers are well established, how the ES cell specific transcriptional and alternative splicing (AS) machinery regulate their expression has not been sufficiently explored. In this study, we show that the lncRNA associated protein TOBF1 regulates the co-transcriptional alternative splicing of transcripts necessary for maintaining stem cell identity in mouse ES cells. Overlaying information derived from TOBF1 chromatin occupancy, the distribution of its pluripotency-associated OCT-SOX binding motifs, and transcripts undergoing differential expression and alternative splicing upon its disruption unmasked local nuclear territories where these distinct events converge, ultimately leading to the maintenance of mouse ES cell identity.

developmental biology↗

bioRxiv2022

An Open-Source Rodent Chronic EEG Array System with High Density MXene-Based Skull Surface Electrodes

Electroencephalography (EEG) is an indispensable tool in epilepsy, sleep, and behavioral research. In rodents, EEG recordings are typically performed with metal electrodes that traverse the skull into the epidural space. In addition to requiring a major surgery, this intracranial EEG technique is difficult to perform for more than a few electrodes, is time-intensive, and confounds experiments studying traumatic brain injury. Here, we describe an open-source cost-effective refinement of this technique for chronic mouse EEG recording. Our alternative two channel (EEG2) and sixteen channel high-density EEG (HdEEG) arrays use electrodes made of the novel, flexible 2D nanomaterial titanium carbide (Ti3C2Tx) MXene. The MXene electrodes are placed on the surface of the intact skull and establish electrical connection without conductive gel or paste. Fabrication and implantation times of MXene EEG electrodes are significantly shorter than the standard approach and recorded resting baseline and epileptiform EEG waveforms are similar to those obtained with traditional epidural electrodes. Applying HdEEG to a mild traumatic brain injury (mTBI) model in mice of both sexes revealed that mTBI significantly altered awake resting state spectral density with a spatiospectral region of interest in the {beta} spectral band (12-30 Hz) in the central and posterior regions. These findings indicate that fabrication of MXene electrode arrays is a cost effective, efficient technology for multichannel EEG recording in rodents that obviates the need for skull-penetrating surgery. Moreover, increased {beta} spectral power may contribute to the development of early post-mTBI seizures. Significance StatementElectroencephalography (EEG) is a critical technique used to study neurological activity in rodents. Commonly used EEG procedures require time-consuming skull-penetrating surgeries that may confound the experiments. Here we provide a cost-effective solution for obtaining two channel (EEG2) and high-density EEG (HdEEG) recordings on the skull surface thus avoiding major surgery. We compared this HdEEG system to traditional EEG recordings and then used it to determine the effects of mild traumatic brain injury on awake resting state spectral density. This novel open-source EEG system will contribute the electrophysiological characterization of rodent behaviors and seizure activity.

neuroscience↗

bioRxiv2022

Antigen presentation by clonally diverse CXCR5+ B cells to CD4 and CD8 T cells is associated with durable response to immune checkpoint inhibitors.

The mechanism by which ICI (immune checkpoint inhibitor) induce durable antitumor T cell activity remains inadequately defined. Tumors from melanoma patients who responded to ICI or MAPK pathway inhibitors (MAPKi) therapy generally displayed increased T cell infiltration and interferon gamma (IFN{gamma}) pathway activation. Yet, the rate of durable tumor control after ICI is almost twice that of MAPKi. Comparing the transcriptome of cohorts of melanoma patients treated with ICI or MAPKi therapy, we discovered that response to ICI is associated with CXCL13-driven recruitment of CXCR5+ B cells with higher clonal diversity than MAPKi. Higher B cell receptor (BCR) diversity allows presentation of diverse tumor antigens by B cells, resulting in robust increases of IFN{gamma} pathway activity and CXCL13 expression in tumor reactive CD8 T cells after ICI therapy. Accordingly, ICI-treated melanoma patients, but not MAPKi, whose tumors displayed higher BCR diversity and IFN{gamma} pathway score, survived significantly longer than those with either one or none. Thus, response to ICI, but not to MAPKi therapy, induces the recruitment of clonally diverse antigen presenting B cells that activate tumor specific, cytotoxic CD8 T cells to effect a durable antitumor immune response. Our result suggests that enhancing B cells tumor antigen presentation to intratumoral CD8 T cells can increase the rate of long-term response to ICI therapy.

cancer biology↗

bioRxiv2022

A novel method revealing animal evolutionary relationships based on milk Mid-infrared

Mid-infrared spectra (MIRS) can effectively reflect the chemical bonds in milk, which has been widely used in dairy herd improvement. However, the relationship between MIRS and animal evolution remains largely unclear. This study firstly found great differences in MIRS and the components of milk by analyzing MIRS information of 12 different mammal species. A five-level discriminant model of evolutionary level based on MIRS was established with a test set kappa coefficient >0.97. In addition, a regression model of genetic distance was also established to estimate the genetic distance of different animal species with a correlation coefficient of R >0.94. These results showed that this method could be used for accurate mammalian evolutionary relationship assessment. We further clarified the potential relationship between MIRS and genes, such as PPP3CA and SCD that could change MIRS by regulating specific milk components. In conclusion, we expand the application of MIRS in animal species identification and evolution research and provide new perspectives for the research on the formation mechanism of different animal milk special components.

evolutionary biology↗

bioRxiv2022

Streptomyces alleviate abiotic stress in plant by producing pteridic acids

Soil microbiota can confer fitness advantages to plants and increase crop resilience to drought and other abiotic stressors. However, there is little evidence on the mechanisms correlating a microbial trait with plant abiotic stress tolerance. Here, we report that Streptomyces effectively alleviates the drought and salinity stress by producing spiroketal polyketide pteridic acid H (1) and its isomer F (2), both of which promote root growth in Arabidopsis at a concentration of 1.3 nM under abiotic stress. Pteridic acids induce stress response genes expression in salinity-stressed Arabidopsis seedlings. The bifunctional biosynthetic gene cluster of pteridic acids and antimicrobial elaiophylin is confirmed in vivo and mainly disseminated by vertical transmission which is geographically distributed in various environments. This discovery reveals a perspective for understanding plant-Streptomyces interactions and provides a promising approach for utilising beneficial Streptomyces and their secondary metabolites in agriculture to mitigate the detrimental effects of climate change.

microbiology↗

bioRxiv2022

Evaluation of antibody kinetics and durability in health subjects vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China

BackgroundAlthough inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. MethodsWe enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. ResultsOur results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The NAb inhibition rate subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89) to 17.8% (16/90). ConclusionsTwo doses of CoronaVac vaccine resulted in limited protection over a short duration. The homologous booster slightly increased antibody responses to the Delta and Omicron variants; therefore, the optimization of booster procedures is vital. FundingKey Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation.

immunology↗

bioRxiv2022

Whole Human-Brain Mapping of Single Cortical Neurons for Profiling Morphological Diversity and Stereotypy

Quantification of individual cells morphology and their distribution at the whole brain scale is essential to understand the structure and diversity of cell types. Despite recent technological advances, especially single cell labeling and whole brain imaging, for many prevailing animal models, it is exceedingly challenging to reuse similar technologies to study human brains. Here we propose Adaptive Cell Tomography (ACTomography), a low-cost, high-throughput, high-efficacy tomography approach, based on adaptive targeting of individual cells suitable for human-brain scale modeling of single neurons to characterize their 3-D structures, statistical distributions, and extensible for other cellular features. Specifically, we established a platform to inject dyes into cortical neurons in surgical tissues of 18 patients with brain tumors or other conditions and 1 donated fresh postmortem brain. We collected 3-D images of 1746 cortical neurons, of which 852 neurons were subsequentially reconstructed to quantify their local dendritic morphology, and mapped to standard atlases both computationally and semantically. In our data, human neurons are more diverse across brain regions than by subject age or gender. The strong stereotypy within cohorts of brain regions allows generating a statistical tensor-field of neuron morphology to characterize 3-D anatomical modularity of a human brain.

neuroscience↗

bioRxiv2022

Neural Representations of Post-Decision Choice Confidence and Reward Expectation in the Caudate Nucleus and Frontal Eye Field

Performance monitoring that supports ongoing behavioral adjustments is often examined in the context of either choice confidence for perceptual decisions (i.e., "did I get it right?") or reward expectation for reward-based decisions (i.e., "what reward will I receive?"). However, our understanding of how the brain encodes these distinct evaluative signals remains limited because they are easily conflated, particularly in commonly used two-alternative tasks with symmetric rewards for correct choices. Previously we reported behavioral and neural results related to decision formation by monkeys performing a visual motion discrimination task with asymmetric rewards (Doi et al., 2020; Fan et al., 2020). Here we leveraged this task design to partially decouple trial-by-trial estimates of choice confidence and reward expectation and examine their impacts on behavior and their representations in the caudate nucleus (part of the striatum in the basal ganglia) and the frontal eye field (FEF, in prefrontal cortex). We found that these evaluative signals had infrequent, but consistent, effects on the behavior of well-trained monkeys. We also identified distinguishable representations of the two types of signals in FEF and caudate neurons, including different distribution patterns, time courses, and relationships to behavior in the two brain areas. These results suggest that the cortico-striatal decision network may use diverse evaluative signals for performance monitoring and add to our understanding of the different roles of the FEF and caudate nucleus in decision-related computations.

neuroscience↗

bioRxiv2022

Insulin signaling and extended longevity in ants

In most organisms, the cost of reproduction is a shorter lifespan. However, the reproductive caste in eusocial insect species (queen) exhibits an extraordinarily longer lifespan than non-reproductive castes (workers) despite having a similar genome, thus contradicting the aging dogma. In the absence of the queen, Harpegnathos saltator ants can undergo a caste switch from workers to reproductive pseudo-queens (gamergates). Gamergates exhibit a dramatically prolonged lifespan. When placed in the presence of a reproductive, they revert to worker status and their lifespan is then shortened accordingly. To understand this unique relationship between reproduction and longevity, we analyzed tissue-specific gene expression between castes. Insulin is upregulated in the gamergate brain that leads to oogenesis, but surprisingly correlates with extended longevity. This correlates with increased lipid synthesis and elevated production of vitellogenin in the fat body, which are both transported to the egg. We show that the production of vitellogenin in the fat body is due to the systemic activation of the MAPK branch of the insulin/IGF signaling (IIS)-pathway. In contrast, reduced expression of insulin receptors in the fat body of gamergates and the production in their developing ovary of an anti-insulin (Imp-L2) lead to the downregulation of the AKT/FOXO branch of the IIS-signaling pathway in the fat body, and to the dramatically extended longevity. This reveals a dual-pathway mechanism that reconciles increased longevity in the context of active reproduction in eusocial insects. One Sentence SummaryInsulin-dependent reproduction in ants correlates with extended longevity through insulin inhibition by anti-insulin Imp-L2.

physiology↗

bioRxiv2022

Charting the Spatial Landscape of Cancer Hallmarks

Tumors are complex ecosystems with dozens of interacting cell types. The concept of Cancer Hallmarks distills this complexity into a set of underlying principles that govern tumor growth. Here, we exploit this abstraction to explore the physical distribution of Cancer Hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that Hallmark activity is spatially organized-with 7 out of 13 Hallmarks consistently more active in cancer cells than within the non-cancerous tumor microenvironment (TME). The opposite is true for the remaining six Hallmarks. Additionally, we discovered that genomic distance between tumor subclones correlates with differences in Cancer Hallmark activity, even leading to clone-Hallmark specialization in some cases. Finally, we demonstrate interdependent relationships between Cancer Hallmarks at the junctions of TME and cancer compartments. In conclusion, including the spatial dimension, particularly through the lens of Cancer Hallmarks, can improve our understanding of tumor ecology. SignificanceWe explored Cancer Hallmarks in 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. This study unveiled spatial patterns in Hallmark activity, with some being more active in cancer cells and others in the non-cancerous tumor environment. Genomic distance impacted Hallmark activity, and we identified interdependencies at the TME-cancer junctions, improving our understanding of tumor ecology.

cancer biology↗

bioRxiv2022

Arf GTPase activates the WAVE Regulatory Complex through a novel binding site

Crosstalk between Rho- and Arf-family GTPases plays an important role in linking actin cytoskeletal remodeling to membrane protrusion, organelle structure, and vesicle trafficking. The central actin regulator, WAVE Regulatory Complex (WRC), is a converging point of Rac1 (a Rho-family GTPase) and Arf signaling in many processes, but how Arf promotes WRC activation is unknown. Here we reconstituted a direct interaction between Arf and WRC. This interaction can be greatly enhanced by Rac1 binding to the D site of the WRC. Arf1 binds to a newly identified conserved surface on Sra1 located between the D site and the WH2 helix of WAVE1, which can drive WRC activation using a mechanism distinct from that of Rac1. Mutating Arf binding site abolishes Arf1-WRC interaction, disrupts Arf1-mediated WRC activation, and impairs lamellipodia morphology. This work uncovers a new mechanism underlying WRC activation and provides a mechanistic foundation for studying how WRC-mediated actin polymerization links Arf and Rac signaling in the cell.

biochemistry↗

bioRxiv2022

Sequential functional differentiation of luminal epithelial cells regulated by maternal and embryonic signaling in the mouse endometrium

Embryo implantation requires temporospatial maternal-embryo dialog to regulate the interactions between an activated blastocyst and a receptive endometrium; however, the details of the related cell-specific coordination is largely unknown because of the cellular complexity and dynamic developmental processes of both the embryo and endometrium during peri-implantation. By comparing single-cell RNA (scRNA) data obtained from entire uteri of pregnant and pseudo-pregnant mice with embryos that were in the oviduct (dpc2.5 days post-coitum [dpc]) or had entered the uterus (after 3.5 dpc), we found a maternal estrogen and progesterone signaling-dependent functional differentiation process in which progesterone induced estrogen-responsive luminal epithelial cells to differentiate into two new types of epithelial cells: adhesion epithelial cells (AECs) and supporting epithelial cells (SECs) on 2.5 dpc. In addition to maternal signaling data, the uterine scRNA and corresponding embryo bulk sequencing data were obtained, and analyses revealed that embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, enhancing the attachment of embryos to the endometrium after implantation. Specifically, embryonic signaling induced additional transformation of AECs by preventing adjacent AECs, but not AECs away from the embryo in the implantation chamber, from undergoing apoptosis. Furthermore, we demonstrated that epithelial cell differentiation and related regulatory signaling were largely conserved in humans and mice. In the human endometrium, developmental defects of SOX9-positive epithelial cells similar to luminal epithelial cells were related to thin endometrium. Our work provides comprehensive and systematic information on endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is important for endometrial receptivity and embryo implantation.

cell biology↗

bioRxiv2022

Pancreas resident macrophage-induced fibrosis has divergent roles in pancreas inflammatory injury and PDAC

Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages (MDMs). However, whether TRMs and MDMs have functional distinction under differing pathologies is not understood. Here, we show a significant portion of macrophages that accumulated during pancreatitis and pancreatic cancer were expanded from TRMs. We further established that pancreas TRMs have a distinct extracellular matrix remodeling phenotype that was critical for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and animal death, due to impaired acinar cell survival and recovery. In pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.

immunology↗

bioRxiv2021

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2

The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social and economic stability. In this study, we established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. This platform is a rapid, sensitive, specific, and high throughput system. With this platform, we screened two compound libraries of 2,864 molecules and identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S-protein and the human cell ACE2 receptor. This data suggests that TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug. SIGNIFICANCEThe ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. In this present study, we screened two compound libraries of 2,864 molecules and identified a potent inhibitor (TS-984) for blocking the coronavirus S-protein and the human cell ACE2 receptor. TS-984 might have the potential to be developed into an effective anti-coronavirus drug for treating COVID-19.

pharmacology and toxicology↗