Biology subjects

Wang, N.

Publications and source records attributed to Wang, N..

At least 271 records · Page 15Linked to original sources

bioRxiv2021

Aplp1 and the Aplp1-Lag3 Complex facilitates transmission of pathologic alpha-synuclein

Pathologic -synuclein (-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid {beta} precursor-like protein 1 (Aplp1) forms a complex with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic -syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by -syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of -syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by -syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for -syn PFF induced pathology advances our understanding of the molecular mechanism of cell-to-cell transmission of pathologic -syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinsons disease and related -synucleinopathies. One Sentence SummaryAplp1 forms a complex with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic -synuclein. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/442157v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1d746bforg.highwire.dtl.DTLVardef@65acb2org.highwire.dtl.DTLVardef@12cf2f0org.highwire.dtl.DTLVardef@19d6e_HPS_FORMAT_FIGEXP M_FIG Aplp1 and the Aplp1-Lag3 complex facilitates transmission of pathologic -synuclein. Aplp1 is a receptor that drives pathologic -syn transmission, and genetic depletion of Aplp1 can significantly reduce the -synuclein pathogenesis. Aplp1 and Lag3 forms an Aplp1-Lag3 complex that accounts for substantial binding of pathologic -syn to cortical neurons. Together Aplp1 and Lag3 play a major role in pathologic -syn internalization, transmission and toxicity. Double knockout of Aplp1 and Lag3 and or a Lag3 antibody that disrupts the Aplp1 and Lag3 complex almost completely blocks -syn PFF-induced neurodegeneration. C_FIG

neuroscience↗

bioRxiv2021

Exosome component 1 cleaves single-stranded DNA and sensitizes kidney renal clear cell carcinoma cells to poly(ADP-ribose) polymerase inhibitor

Targeting DNA repair pathway offers an important therapeutic strategy for cancers. However, the failure of DNA repair inhibitors to markedly benefit patients necessitates the development of new strategies. Here, we show that exosome component 1 (EXOSC1) promotes DNA damages and sensitizes kidney renal clear cell carcinoma (KIRC) cells to DNA repair inhibitor. Considering that endogenous source of mutation (ESM) constantly assaults genomic DNA and likely sensitize cancer cells to the inhibitor, we first analyzed the statistical relationship between the expression of individual genes and the mutations for KIRC. Among the candidates, EXOSC1 most notably promoted DNA damages and subsequent mutations via preferentially cleaving C site(s) in single-stranded DNA. Consistently, EXOSC1 was more significantly correlated with C>A transversions in coding strands than these in template strands in KIRC. Notably, KIRC patients with high EXOSC1 showed a poor prognosis, and EXOSC1 sensitized cancer cells to poly(ADP-ribose) polymerase inhibitor. These results show that EXOSC1 acts as an ESM in KIRC, and targeting EXOSC1 might be a potential therapeutic strategy.

cancer biology↗

bioRxiv2021

Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

synthetic biology↗

bioRxiv2021

Structural basis for HCMV Pentamer recognition by antibodies and neuropilin 2

Human cytomegalovirus (HCMV) encodes for multiple surface glycoproteins and glycoprotein complexes1, 2. One of these complexes, the HCMV Pentamer (gH, gL, UL128, UL130 and UL131), mediates tropism to both epithelial and endothelial cells by interacting with the cell surface receptor neuropilin 2 (NRP2)3, 4. Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here we describe the cryo-EM structure of NRP2 bound to the HCMV Pentamer. The high-affinity interaction between these proteins is calcium-dependent and differs from the canonical C-terminal arginine (CendR) binding that NRP2 typically utilizes5, 6. The interaction is primarily mediated by NRP2 domains a2 and b2, which interact with UL128 and UL131. We also determine the structures of four human-derived neutralizing antibodies in complex with the HCMV Pentamer to define susceptible epitopes. The two most potent antibodies recognize a novel epitope yet do not compete with NRP2 binding. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization, and serve as a guide for the development of HCMV treatments and vaccines.

microbiology↗

bioRxiv2021

From atoms to cells: bridging the gap between potency, efficacy, and safety of small molecules directed at a membrane protein

Membrane proteins constitute a substantial fraction of the human proteome, thus representing a vast source of therapeutic drug targets. Indeed, newly devised technologies now allow targeting "undruggable" regions of membrane proteins to modulate protein function in the cell. Despite the advances in technology, the rapid translation of basic science discoveries into potential drug candidates targeting transmembrane protein domains remains challenging. We address this issue by harmonizing single molecule-based and ensemble-based atomistic simulations of ligand-membrane interactions with patient-derived induced pluripotent stem cell (iPSC)-based experiments to gain insights into drug delivery, cellular efficacy, and safety of molecules directed at membrane proteins. In this study, we interrogated the pharmacological activation of the cardiac Ca2+ pump (Sarcoplasmic reticulum Ca2+-ATPase, SERCA2a) in human iPSC-derived cardiac cells as a proof-of-concept model. The combined computational-experimental approach serves as a platform to explain the differences in the cell-based activity of candidates with similar functional profiles, thus streamlining the identification of drug-like candidates that directly target SERCA2a activation in human cardiac cells. Systematic cell-based studies further showed that a direct SERCA2a activator does not induce cardiotoxic pro-arrhythmogenic events in human cardiac cells, demonstrating that pharmacological stimulation of SERCA2a activity is a safe therapeutic approach targeting the heart. Overall, this novel platform encompasses organ-specific drug potency, efficacy, and safety, and opens new avenues to accelerate the bench-to-patient research aimed at designing effective therapies directed at membrane protein domains.

pharmacology and toxicology↗

bioRxiv2021

DNA Methylation Networks Underlying Mammalian Traits

Epigenetics has hitherto been studied and understood largely at the level of individual organisms. Here, we report a multi-faceted investigation of DNA methylation across 11,117 samples from 176 different species. We performed an unbiased clustering of individual cytosines into 55 modules and identified 31 modules related to primary traits including age, species lifespan, sex, adult species weight, tissue type and phylogenetic order. Analysis of the correlation between DNA methylation and species allowed us to construct phyloepigenetic trees for different tissues that parallel the phylogenetic tree. In addition, while some stable cytosines reflect phylogenetic signatures, others relate to age and lifespan, and in many cases responding to anti-aging interventions in mice such as caloric restriction and ablation of growth hormone receptors. Insights uncovered by this investigation have important implications for our understanding of the role of epigenetics in mammalian evolution, aging and lifespan.

evolutionary biology↗

bioRxiv2021

Genome-wide transcriptome and translatome analyses reveal the role of protein extension and domestication in liver cancer oncogenesis

One gene could be transcribed to different RNA isoforms, and then produce various forms of protein sequences. This mechanism largely diversifies the cellular pool and allows natural selection to select from a wider range of substrates. Most of the deleterious changes should be either purged or only be observed in patients with deficiencies or diseases. In the cancer field, the "intra-gene" changes between tumor and normal tissues such as the alternative splicing, stop codon read-through, or protein domestication could not be captured by differential expression analyses. In this work, we collected public transcriptome and translatome data from ten patients with liver cancer, and performed genome-wide comparison on the stop codon read-through and protein domestication events. Both events could diversify the proteome without changing the genome sequence. Surprisingly, we found that compared to normal tissues, the tumor tissues globally have significantly higher occurrence of stop codon read-through events. Similarly, the translation signals of non-coding repetitive elements (protein domestication) are elevated in tumor samples. These read-through and domestication events show limited overlapping across the ten patients, suggesting the randomness of the occurrence. It also indicates that these tumor-specific read-through and domestication events should be deleterious, and should be purged by natural selection if they are not collected timely. Our work manifests the role of protein extension and domestication in liver cancer oncogenesis, and adds new aspects to the cancer field.

genomics↗

bioRxiv2021

Enabling technology for microbial source tracking based on transfer learning: From ontology-aware general knowledge to context-aware expert systems

Microbial source tracking quantifies the potential origin of microbial communities, facilitates better understanding of how the taxonomic structure and community functions were formed and maintained. However, previous methods involve a tradeoff between speed and accuracy, and have encountered difficulty in source tracking under many context-dependent settings. Here, we present EXPERT for context-aware microbial source tracking, in which we adopted a Transfer Learning approach to profoundly elevate and expand the applicability of source tracking, enabling biologically informed novel microbial knowledge discovery. We demonstrate that EXPERT can predict microbial sources with performance superior to other methods in efficiency and accuracy. More importantly, we demonstrate EXPERTs context-aware ability on several applications, including tracking the progression of infant gut microbiome development and monitoring the changes of gut microbiome for colorectal cancer patients. Broadly, transfer learning enables accurate and context-aware microbial source tracking and has the potential for novel microbial knowledge discovery.

bioinformatics↗

bioRxiv2021

Surface-based Single-subject Morphological Brain Networks: Effects of Morphological Index, Brain Parcellation and Similarity Measure, Sample Size-varying Stability and Test-retest Reliability

Morphological brain networks, in particular those at the individual level, have become an important approach for studying the human brain connectome; however, relevant methodology is far from being well-established in their formation, description and reproducibility. Here, we extended our previous study by constructing and characterizing single-subject morphological similarity networks from brain volume to surface space and systematically evaluated their reproducibility with respect to effects of different choices of morphological index, brain parcellation atlas and similarity measure, sample size-varying stability and test-retest reliability. Using the Human Connectome Project dataset, we found that surface-based single-subject morphological similarity networks shared common small-world organization, high parallel efficiency, modular architecture and bilaterally distributed hubs regardless of different analytical strategies. Nevertheless, quantitative values of all interregional similarities, global network measures and nodal centralities were significantly affected by choices of morphological index, brain parcellation atlas and similarity measure. Moreover, the morphological similarity networks varied along with the number of participants and approached stability until the sample size exceeded [~]70. Using an independent test-retest dataset, we found fair to good, even excellent, reliability for most interregional similarities and network measures, which were also modulated by different analytical strategies, in particular choices of morphological index. Specifically, fractal dimension and sulcal depth outperformed gyrification index and cortical thickness, higher-resolution atlases outperformed lower-resolution atlases, and Jensen-Shannon divergence-based similarity outperformed Kullback-Leibler divergence-based similarity. Altogether, our findings propose surface-based single-subject morphological similarity networks as a reliable method to characterize the human brain connectome and provide methodological recommendations and guidance for future research.

neuroscience↗

bioRxiv2021

Evaluation of deep convolutional neural networks for in situ hybridization gene expression image representation

High resolution in situ hybridization (ISH) images of the brain capture spatial gene expression at cellular resolution. These spatial profiles are key to understanding brain organization at the molecular level. Previously, manual qualitative scoring and informatics pipelines have been applied to ISH images to determine expression intensity and pattern. To better capture the complex patterns of gene expression in the human cerebral cortex, we applied a machine learning approach. We propose gene re-identification as a contrastive learning task to compute representations of ISH images. We train our model on a ISH dataset of ~1,000 genes obtained from postmortem samples from 42 individuals. This model reaches a gene re-identification rate of 38.3%, a 13x improvement over random chance. We find that the learned embeddings predict expression intensity and pattern. To test generalization, we generated embeddings in a second dataset that assayed the expression of 78 genes in 53 individuals. In this set of images, 60.2% of genes are re-identified, suggesting the model is robust. Importantly, this dataset assayed expression in individuals diagnosed with schizophrenia. Gene and donor-specific embeddings from the model predict schizophrenia diagnosis at levels similar to that reached with demographic information. Mutations in the most discriminative gene, SCN4B, may help understand cardiovascular associations with schizophrenia and its treatment. We have publicly released our source code, embeddings, and models to spur further application to spatial transcriptomics. In summary, we propose and evaluate gene re-identification as a machine learning task to represent ISH gene expression images.

neuroscience↗

bioRxiv2021

De novo assembly, annotation, and comparative analysis of 26 diverse maize genomes

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The data indicate that the number of pan-genes exceeds 103,000 and that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres further reveal the locations and internal structures of major cytological landmarks. We show that combining structural variation with SNPs can improve the power of quantitative mapping studies. Finally, we document variation at the level of DNA methylation, and demonstrate that unmethylated regions are enriched for cis-regulatory elements that overlap QTL and contribute to changes in gene expression. One sentence summaryA multi-genome analysis of maize reveals previously unknown variation in gene content, genome structure, and methylation.

genomics↗

bioRxiv2021

An intrinsically disordered intracellular domain of PIEZO2 is required for force-from-filament activation of the channel

A central question in mechanobiology is how mechanical forces acting in or on a cell are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we show that PIEZO2 is sensitive to force-transmission via the membrane (force-from-lipids) as well as force transmission via the cytoskeleton (force-from-filament) and demonstrate that the latter requires the intracellular linker between the transmembrane helices nine and ten (IDR5). Moreover, we show that rendering PIEZO2 insensitive to force-from-filament by deleting IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, which relies on the detection of cellgenerated traction forces, while it only partially affects its sensitivity to cell indentation and does not at all alter its sensitivity to membrane stretch. Hence, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO channel function.

neuroscience↗

bioRxiv2021

Single-cell and single-variant resolution analysis of clonal evolution in human liver cancer

Genetic heterogeneity of tumor is closely related to clonal evolution, phenotypic diversity and treatment resistance. Such heterogeneity has been characterized in liver cancer at single-cell sub-chromosomal scale, and a more precise single-variant resolution analysis is lacking. Here we employed a strategy to analyze both the single-cell genomic mutations and transcriptomic changes in 5 patients with liver cancer. Target sequencing was done for a total of 480 single cells in a patient-specific manner. DNA copy number status of point mutations was obtained from single-cell mutational profiling. The clonal structures of liver cancers were then uncovered at single-variant resolution, and mutation combinations in single cells enabled reconstruction of their evolutionary history. A common origin but independent evolutionary fate was revealed for primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. The mutational signature suggested early evolutionary process may be related to specific etiology like aristolochic acids. By parallel single-cell RNA-Seq, the transcriptomic phenotype was found to be related with genetic heterogeneity in liver cancer. We reconstructed the single-cell and single-variant resolution clonal evolutionary history of liver cancer, and dissection of both genetic and phenotypic heterogeneity provides knowledge for mechanistic understanding of liver cancer initiation and progression.

genomics↗

bioRxiv2020

A high-quality genome of the mangrove Aegiceras corniculatum aids investigation of molecular adaptation to intertidal environments

Mangroves have colonized extreme intertidal environments characterized by high salinity, hypoxia, and other abiotic stresses. During millions of years of evolution, mangroves have adapted to these habitats, evolving a series of highly specialized traits. Aegiceras corniculatum, a pioneer mangrove species that evolved salt secretion and crypto-vivipary, is an attractive ecological model to investigate molecular mechanisms underlying adaptation to intertidal environments. Here we report a high-quality reference genome of A. corniculatum using the PacBio SMRT sequencing technology, comprising 827 Megabases (Mb) and containing 32,092 protein-coding genes. The longest scaffold and N50 for the assembled genome are 13.76 Mb and 3.87 Mb. Comparative and evolutionary analyses revealed that A. corniculatum experienced a whole-genome duplication (WGD) event around 35 million years ago after the divergence between Aegiceras and Primula. We inferred that maintenance of cellular environmental homeostasis is an important adaptive process in A. corniculatum. The 14-3-3 protein-coding genes were retained after the recent WGD event, decoding a calcium signal to regulate Na+ homeostasis. A. corniculatum has more H+-ATPase coding genes, essential for the maintenance of low Na+ concentration in the cells, than its relatives. Photosynthesis and oxidative-phosphorylation pathways are overrepresented among significantly expanded gene families and might supply the energy needed for salt secretion. Genes involved in natural antioxidant biosynthesis, contributing to scavenging reactive oxygen species against high salinity, have also increased in copy number. We also found that all homologs of DELAY OF GERMINATION1 (DOG1), a pivotal regulator of seed dormancy, lost their heme-binding ability in A. corniculatum. This loss may contribute to crypto-vivipary. Our study provides a valuable resource to investigate molecular adaptation to extreme environments in mangroves.

genomics↗

bioRxiv2020

Towards understanding interindividual differences in cortical morphological brain networks

Individual-level morphological brain networks are becoming an important approach for studying human connectome; however, their interindividual differences are not well understood with respect to behavioral and cognitive relevance, individual identification, and genetic origin. Using three publicly available datasets that involved cross-sectional and longitudinal structural magnetic resonance scans of adults and children, we constructed four morphological brain networks for each of 1,451 images from 1,329 participants on the basis of cerebral surface-based, vertex-wise cortical thickness, fractal dimension, gyrification index and sulcal depth, respectively. The morphological index-dependent networks were further fused via multiplex network model, and fed into community detection. We found that the multiplex morphological brain networks 1) accounted for significant proportions of interindividual variance in and were predictive of multiple behavioral and cognitive domains, in particular Cognition and Motor domains (P < 0.05, corrected), 2) distinguished individuals from each other with high accuracies even for twin subjects (accuracies > 96%), and 3) exhibited low-moderate heritability with the highest for sulcal depth-based morphological brain networks. Intriguingly, compared with intra-module morphological connectivity, inter-module connections explained more behavioral and cognitive variance and were associated with higher heritability. Further comparisons revealed that multiplex morphological brain networks outperformed each type of single-layer morphological brain networks in the performance of behavioral and cognitive association and prediction, and individual identification. Finally, all the findings were generally reproducible over different datasets. Altogether, our findings indicate that interindividual differences in individual-level morphological brain networks are biologically meaningful, which underpins their usage as fingerprints for individualized studies in health and disease.

neuroscience↗

bioRxiv2020

Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes in COVID-19 convalescent plasma

Although humoral immunity is essential for control of SARS-CoV-2, the molecular composition, binding epitopes and effector functions of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following infection are unknown. Proteomic deconvolution of the circulating IgG repertoire (Ig-Seq1) to the spike ectodomain (S-ECD2) in four convalescent study subjects revealed that the plasma response is oligoclonal and directed predominantly (>80%) to S-ECD epitopes that lie outside the receptor binding domain (RBD). When comparing antibodies directed to either the RBD, the N-terminal domain (NTD) or the S2 subunit (S2) in one subject, just four IgG lineages (1 anti-S2, 2 anti-NTD and 1 anti-RBD) accounted for 93.5% of the repertoire. Although the anti-RBD and one of the anti-NTD antibodies were equally potently neutralizing in vitro, we nonetheless found that the anti-NTD antibody was sufficient for protection to lethal viral challenge, either alone or in combination as a cocktail where it dominated the effect of the other plasma antibodies. We identified in vivo protective plasma anti-NTD antibodies in 3/4 subjects analyzed and discovered a shared class of antibodies targeting the NTD that utilize unmutated or near-germline IGHV1-24, the most electronegative IGHV gene in the human genome. Structural analysis revealed that binding to NTD is dominated by interactions with the heavy chain, accounting for 89% of the entire interfacial area, with germline residues uniquely encoded by IGHV1-24 contributing 20% (149 [A]2). Together with recent reports of germline IGHV1-24 antibodies isolated by B-cell cloning3,4 our data reveal a class of shared IgG antibodies that are readily observed in convalescent plasma and underscore the role of NTD-directed antibodies in protection against SARS-CoV-2 infection.

immunology↗

bioRxiv2020

Cross-reactive coronavirus antibodies with diverse epitope specificities and extra-neutralization functions

The continual emergence of novel coronavirus (CoV) strains, like SARS-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. Coronavirus spike (S) proteins share common structural motifs that could be vulnerable to cross-reactive antibody responses. To study this phenomenon in human coronavirus infection, we applied a high-throughput sequencing method called LIBRA-seq (Linking B cell receptor to antigen specificity through sequencing) to a SARS-CoV-1 convalescent donor sample. We identified and characterized a panel of six monoclonal antibodies that cross-reacted with S proteins from the highly pathogenic SARS-CoV-1 and SARS-CoV-2 and demonstrated a spectrum of reactivity against other coronaviruses. Epitope mapping revealed that these antibodies recognized multiple epitopes on SARS-CoV-2 S, including the receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Functional characterization demonstrated that the antibodies mediated a variety of Fc effector functions in vitro and mitigated pathological burden in vivo. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies that may be useful for preventing potential future coronavirus outbreaks.

immunology↗

bioRxiv2020

Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19. HighlightsO_LISARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusion C_LIO_LIHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice models C_LIO_LIRhesus macaques showed no adverse side effects when administered with HB27 C_LIO_LICryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor C_LI

biophysics↗