Biology subjects

Zhao, Y.

Publications and source records attributed to Zhao, Y..

At least 847 records · Page 47Linked to original sources

bioRxiv2021

A comprehensive mass spectral library for human thyroid tissues

Thyroid nodules occur in about 60% of the population. Current diagnostic strategies, however, often fail at distinguishing malignant nodules before surgery, thus leading to unnecessary, invasive treatments. As proteins are involved in all physio/pathological processes, a proteome investigation of biopsied nodules may help correctly classify and identify malignant nodules and discover therapeutic targets. Quantitative mass spectrometry data-independent acquisition (DIA) enables highly reproducible and rapid throughput investigation of proteomes. An exhaustive spectral library of thyroid nodules is essential for DIA yet still unavailable. This study presents a comprehensive thyroid spectral library covering five types of thyroid tissue: multinodular goiter, follicular adenoma, follicular and papillary thyroid carcinoma, and normal thyroid tissue. Our library includes 925,330 transition groups, 157,548 peptide precursors, 121,960 peptides, 9941 protein groups, and 9826 proteins from proteotypic peptides. This library resource was evaluated using three papillary thyroid carcinoma samples and their corresponding adjacent normal thyroid tissue, leading to effective quantification of up to 7863 proteins from biopsy-level thyroid tissues.

systems biology↗

bioRxiv2021

Comprehensive Analysis of Spatial Architecture in Primary Liver Cancer

Heterogeneity is the major challenge for cancer prevention and therapy. Here, we firstly constructed high-resolution spatial transcriptomes of primary liver cancers (PLCs) containing 84,823 spots within 21 tissues from 7 patients. The sequential comparison of spatial tumor microenvironment (TME) characteristics from non-tumor to leading-edge to tumor regions revealed that the tumor capsule potentially affects intratumor spatial cluster continuity, transcriptome diversity and immune cell infiltration. Locally, we found that the bidirectional ligand-receptor interactions at the 100 m wide cluster-cluster boundary contribute to maintaining intratumor architecture. Our study provides novel insights for diverse tumor ecosystem of PLCs and has potential benefits for cancer intervention.

cancer biology↗

bioRxiv2021

Golden pompano genome resource enables discovery of valuable gene determining growth traits

One important goal of fish genetic breeding is to identify valuable loci and genes that can facilitate growth and thereby productivity. Few such loci or genes have been identified in golden pompano (Trachinotus ovatus), a species of significant economic value. In this study, we produced a high-quality chromosome-level genome assembly of the golden pompano by de novo sequencing and assemblies for 2 parents and 200 F1 offspring by genome re-sequencing. We exploited these assemblies to identify loci and genes by QTL mapping, Kompetitive Allele Specific PCR (KASP) genotyping, and haplotype-based regional association analysis based on growth records of a 64 biparental and 147 individuals from a naturally occurring population. At a locus 291kb from BSNP21031, we identified a somatostatin receptor type 1-like (designated as gpsstr1) gene in which the BSNP1369 of the promoter region was highly associated with growth. Loss of sstr1a, the homolog of gpsstr1 in zebrafish, caused growth retardation. Sstr1a mediated growth via sstr2 and Wnt-gsk-3{beta} signaling pathways. Our findings provide new insights into the underlying mechanisms controlling growth. Our strategy can serve as an effective way to uncover novel genomic information and facilitate improvement of fish growth.

genomics↗

bioRxiv2021

Automated, high-accuracy, remote measurement of heart rate

Arrhythmia is a marked symptom of many cardiovascular diseases (CVDs). The accurate and timely detection of heart rate can greatly reduce the harm of arrhythmia to people. However, it is still a challenge to robustly and remotely measure heart rate in daily life due to the changing environmental conditions during measurement, such as the varying light intensity, the movement of people, and the uncertain distance between the sensor to people. In this study, we propose a method to accurately measure human heart rate within a distance of 4.5 meters under different light intensities by simply using a surveillance camera. After a 20-second color video of a persons hand is captured by the camera, a method based on the Fast Fourier Transform (FFT) algorithm is designed to extract the blood volume pulse wave to calculate the heart rate. According to the comparison between the real heart rate and results measured by electrocardiography (ECG), the proposed method achieves an accuracy of 95.8% when the measurement is performed within a distance of 4.5 meters and 90% when within 5.0 meters. Our experiments show that when the illuminance varies between 100-1000 lux (lighting level indoor), we still get the correct results. Our experiments also demonstrate that the proposed method accurately obtain heart rate even when the light intensity is below 32 lux (300-500 lux in a workplace environment). The methods strong adaptability to changing environmental conditions makes it applicable to many scenarios, such as homes of the elderly, classrooms, and other public spaces.

physiology↗

bioRxiv2021

Neural dynamics between anterior insular cortex and right supramarginal gyrus dissociate genuine affect sharing from automatic responses to pretended pain

Empathy for pain engages both shared affective responses and self-other distinction. In this study, we addressed the highly debated question of whether neural responses previously linked to affect sharing could result from the perception of salient affective displays. Moreover, we investigated how affect sharing and self-other distinction interact to determine our response to a pain that is either perceived as genuine or pretended (while in fact both were acted for reasons of experimental control). We found stronger activations in regions associated with affect sharing (anterior insula, aIns, and anterior mid-cingulate cortex, aMCC) as well as with affective self-other distinction (right supramarginal gyrus, rSMG), in participants watching video clips of genuine vs. pretended facial expressions of pain. Using dynamic causal modeling (DCM), we then assessed the neural dynamics between the right aIns and rSMG in these two conditions. This revealed a reduced inhibitory effect on the aIns to rSMG connection for genuine compared to pretended pain. For genuine pain only, brain-to-behavior regression analyses highlighted a linkage between this inhibitory effect on the one hand, and pain ratings as well as empathic traits on the other. These findings imply that if the pain of others is genuine and thus calls for an appropriate empathic response, neural responses in the aIns indeed seem related to affect sharing and self-other distinction is engaged to avoid empathic over-arousal. In contrast, if others merely pretend to be in pain, the perceptual salience of their painful expression results in neural responses that are down-regulated to avoid inappropriate affect sharing and social support.

neuroscience↗

bioRxiv2021

Genetic characteristics of human papillomavirus type 16, 18, 52 and 58 in southern China

Persistent infections of high-risk human papillomaviruses (HPVs) are the leading cause of cervical cancers. We collected cervical exfoliated cell samples from females in Changsha city, Hunan Province and obtained 358 viral genomes of four major HPV types, including HPV 16 (n=82), 18 (n=35), 52 (n=121) and 58 (n=100). The lineage/sublineage distribution of the four HPVs confirmed previous epidemiological reports, with the predominant prevailing sublineage as A4 (50%), A1 (37%) and A3 (13%) for HPV16, A1 (83%) for HPV18, B2 (86%) for HPV52 and A1 (65%), A3 (19%) and A2 (12%) for HPV58. We also identified two potentially novel HPV18 sublineages, i.e. A6 and A7. Virus mutation analysis further revealed the presence of HPV16 and HPV58 strains associated with potentially high oncogenicity. These findings expanded our knowledge on the HPV genetic diversity in China, providing valuable evidence to facilitate HPV DNA screening, vaccine effectiveness evaluation and control strategy development.

genomics↗

bioRxiv2021

Clonal inactivation of telomerase promotes accelerated stem cell differentiation

Telomerase is intimately associated with stem cells and upregulated in cancer, where it serves essential roles through its catalytic action in elongating telomeres, nucleoprotein caps that protect chromosome ends1. Overexpression of the telomerase reverse transcriptase (TERT) enhances cell proliferation through telomere-independent means, yet definitive evidence for such a direct role in stem cell function has yet to be revealed through loss-of-function studies. Here, we show that conditional deletion of TERT in spermatogonial stem cells (SSCs) markedly impairs competitive clone formation. Using lineage-tracing from the Tert locus, we find that TERT-expressing SSCs yield long-lived clones, but that selective TERT-inactivation in SSCs causes accelerated stem cell differentiation thereby disrupting clone formation. This requirement for TERT in clone formation is bypassed by expression of a catalytically inactive TERT transgene and occurs independently of the canonical telomerase complex. TERT inactivation induces a genome-wide reduction in open chromatin evident in purified SSCs, but not in committed progenitor cells. Loss of TERT causes reduced activity of the MYC oncogene and transgenic expression of MYC in TERT-deleted SSCs efficiently rescues clone formation. These data reveal a required catalytic activity-independent role for TERT in preventing stem cell differentiation, forge a genetic link between TERT and MYC and suggest new means by which TERT may promote tumorigenesis.

developmental biology↗

bioRxiv2021

A chromosome-level genome assembly and annotation of a maize elite breeding line Dan340

BackgroundMaize is not only one of the most important crops grown worldwide for food, forage, and biofuel, but also an important model organism for fundamental research in genetics and genomics. Owing to its importance in crop science, genetics and genomics, several reference genomes of common maize inbred line (genetic material) have been released, but some genomes of important genetic germplasm resources in maize breeding research are still lacking. The maize cultivar Dan340 is an excellent backbone inbred line of the Luda Red Cob Group with several desirable characteristics, such as disease resistance, lodging resistance, high combining ability, and wide adaptability. FindingsIn this study, we constructed a high-quality chromosome-level reference genome for Dan340 by combining PacBio long HiFi sequencing reads, Illumina short reads and chromosomal conformational capture (Hi-C) sequencing reads. The final assembly of the Dan340 genome was 2,348.72 Mb, including 2,738 contigs and 2,315 scaffolds with N50 of 41.49 Mb and 215.35 Mb, respectively. Repeat sequences accounted for 73.40% of the genome size and 39,733 protein-coding genes were annotated. Analysis of genes in the Dan340 genome, together with those from B73, Mo17 and SK, were clustered into 27,654 gene families. There were 1,806 genes from 359 gene families that were specific to Dan340, of which many had functional gene ontology annotations relating to "porphyrin-containing compound metabolic process", "tetrapyrrole biosynthetic process", and "tetrapyrrole metabolic process". ConclusionsThe completeness and continuity of the genome were comparable to those of other important maize inbred lines. The assembly and annotation of this genome not only facilitates our understanding about of intraspecific genome diversity in maize, but also provides a novel resource for maize breeding improvement. Research AreasGenetics and Genomics; Agriculture, Plant Genetics Data Description

genomics↗

bioRxiv2021

Spike Protein Targeting "Nano-Glue" that Captures and Promotes SARS-CoV-2 Elimination

The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant {beta}-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein (KD < 1 pM) with negligible toxicity in vitro and in vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.

immunology↗

bioRxiv2021

Suppression of endothelial miR-22-3p mediates non-small cell lung cancer cell-induced angiogenesis

MicroRNAs (miRNAs) expressed in endothelial cells (ECs) are powerful regulators of angiogenesis, which is essential for tumor growth and metastasis. Here, we demonstrated that miR-22-3p (miR-22) is preferentially and highly expressed in ECs, while its endothelial level is significantly down-regulated in human non-small cell lung cancer (NSCLC) tissues when compared to matched non-tumor lung tissues. This reduction of endothelial miR-22 is induced by NSCLC cell-secreted tumor necrosis factor (TNF)- and interleukin (IL)-1{beta}. Endothelial miR-22 functions as a potent angiogenesis inhibitor that inhibits all the key angiogenic activities of ECs and consequently NSCLC growth through directly targeting sirtuin (SIRT) 1 and fibroblast growth factor receptor (FGFR) 1 in ECs, leading to inactivation of AKT/mammalian target of rapamycin (mTOR) signaling. These novel findings provide insight into the molecular mechanisms of NSCLC angiogenesis and indicate that endothelial miR-22 represents a potential target for the future anti-angiogenic treatment of NSCLC.

cancer biology↗

bioRxiv2021

Dynamic chromatin regulatory landscape of human CAR T cell exhaustion

Dysfunction in T cells limits the efficacy of cancer immunotherapy1-6. We profiled the epigenome, transcriptome, and enhancer connectome of exhaustion-prone GD2-targeting HA-28z chimeric antigen receptor (CAR) T cells and control CD19-targeting CAR T cells, which present less exhaustion-inducing tonic signaling, at multiple points during their ex vivo expansion7. We found widespread, dynamic changes in chromatin accessibility and 3D chromosome conformation preceding changes in gene expression, notably at loci proximal to exhaustion-associated genes such as PDCD1, CTLA4, and HAVCR2, and increased DNA motif access for AP-1 family transcription factors, which are known to promote exhaustion. Although T cell exhaustion has been studied in detail in mouse, we find that the regulatory networks of T cell exhaustion differ between the species and involve distinct loci of accessible chromatin and cis-regulated target genes in human CAR T cell exhaustion. Deletion of exhaustion-specific candidate enhancers of PDCD1 suppress the expression of PD-1 in an in vitro model of T cell dysfunction and in HA-28z CAR T cells, suggesting enhancer editing as a path forward in improving cancer immunotherapy.

genomics↗

bioRxiv2021

Characterization of a glycolipid glycosyltransferase with broad substrate specificity from the marine bacterium Candidatus Pelagibacter sp. HTCC7211

In the marine environment, phosphorus availability significantly affects the lipid composition in many cosmopolitan marine heterotrophic bacteria, including members of the SAR11 clade and the Roseobacter clade. Under phosphorus stress conditions, non-phosphorus sugar-containing glycoglycerolipids are substitutes for phospholipids in these bacteria. Although these glycoglycerolipids play an important role as surrogates for phospholipids under phosphate deprivation, glycoglycerolipid synthases in marine microbes are poorly studied. In the present study, we biochemically characterized a glycolipid glycosyltransferase (GTcp) from the marine bacterium Candidatus Pelagibacter sp. HTCC7211, a member of the SAR11 clade. Our results showed that GTcp is able to act as a multifunctional enzyme by synthesizing different glycoglycerolipids with UDP-glucose, UDP-galactose, or UDP-glucuronic acid as sugar donors and diacylglycerol as the acceptor. Analyses of enzyme kinetic parameters demonstrated that Mg2+ notably changes the enzymes affinity for UDP-glucose, which improves its catalytic efficiency. Homology modelling and mutational analyses revealed binding sites for the sugar donor and the diacylglycerol lipid acceptor, which provided insights into the retaining mechanism of GTcp with its GT-B fold. A phylogenetic analysis showed that GTcp and its homologs form a group in the GT4 glycosyltransferase family. These results not only provide new insights into the glycoglycerolipid synthesis mechanism in lipid remodelling, but also describe an efficient enzymatic tool for future synthesis of bioactive molecules. ImportanceThe bilayer formed by membrane lipids serves as the containment unit for living microbial cells. In the marine environment, it has been firmly established that phytoplankton and heterotrophic bacteria can substitute phospholipids with non-phosphorus sugar-containing glycoglycerolipids in response to phosphorus limitation. However, little is known about how these glycoglycerolipids are synthesized. Here, we determined the biochemical characteristics of a glycolipid glycosyltransferase (GTcp) from the marine bacterium Candidatus Pelagibacter sp. HTCC7211. GTcp and its homologs form a group in the GT4 glycosyltransferase family, and can synthesize neutral glycolipids (MGlc-DAG and MGal-DAG) and an acidic glycolipid (MGlcA-DAG). We also uncover the key residues for DAG-binding through molecular docking, site-direct mutagenesis and subsequent enzyme activity assays. Our data provide new insights into the glycoglycerolipid synthesis mechanism in lipid remodelling.

microbiology↗

bioRxiv2021

Class I Histone Deacetylases (HDAC1-3) are Histone Lysine Delactylases

Lysine O_SCPLOWLC_SCPLOW-lactylation [K(O_SCPLOWLC_SCPLOW-la)] is a newly discovered histone mark that can be stimulated under conditions of high glycolysis, such as the Warburg effect. K(O_SCPLOWLC_SCPLOW-la) is associated with functions that are different from the widely studied histone acetylation. While K(O_SCPLOWLC_SCPLOW-la) can be introduced by the acetyltransferase p300, histone delactylase enzymes remain unknown. Here, we report the systematic evaluation of zinc- and NAD+-dependent HDACs for their ability to cleave {varepsilon}-N-O_SCPLOWLC_SCPLOW-lactyllysine marks. Our screens identified HDACs 1-3 and SIRT1-3 as delactylases in vitro. HDACs 1-3 show robust activity toward not only K(O_SCPLOWLC_SCPLOW-la) but also K(O_SCPLOWDC_SCPLOW-la) and diverse short-chain acyl modifications. We further confirmed the de-O_SCPLOWLC_SCPLOW-lactylase activity of HDACs 1 and 3 in cells. Identification of p300 and HDAC3 as regulatory enzymes suggests that histone lactylation is installed and removed by enzymes as opposed to spontaneous chemical reactivity. Our results therefore represent an important step toward full characterization of this pathways regulatory elements.

biochemistry↗

bioRxiv2021

Single cell transcriptome analysis of decidua macrophages in normal and recurrent spontaneous abortion patients

Due to the heterogeneity and different polarization state of decidual macrophages (dM{Phi}), they play an important role during the pregnancy, but their definition and exact function remain elusive. We isolated CD14+CD45+ dM{Phi} from the normal or RSA decidua by flow cytometry, followed by single cell RNA sequencing (scRNA-seq). In total, 23,062 single-cell transcriptomes of macrophage were profiled (12,470 Normal and 10,592 RSA), which were divided into 13 major clusters via T-distributed stochastic neighbor embedding (t-SNE) visualization. We observed that there is higher percentage composition of M1 cells (70.6%) in the normal decidua, and higher percentage composition of M2 cells (68.3%) in the RSA decidua. We identified new markers (M1: S100A8, S100A9, M2: SELENOP, FOLR2, RNASE1) and secreted cytokines (M1: IL1{beta}, TNFSF13B and MMP9; M2: CCL3, CCL4) of the dM{Phi}. We found that cluster 10 as the specific cluster of dM{Phi} highly expressing BAG3 in normal group and cluster 7 specific highly expressing CXCL9/10/11 chemokine. After pseudo-time trajectory analysis, we found that the dM{Phi} formed a continuous "V-shaped" trajectory, with M1 and M2 type cells mainly occupying the two heads. We found that NF{kappa}B1, MYC and TCF12 acted as the key transcription factors of dM{Phi}. Our study redefined the polarization state and physiological characteristic of dM{Phi} in early normal and RSA pregnancy, which suggests a novel view and therapeutic target for spontaneous abortion prevention.

cell biology↗

bioRxiv2021

Loss of Endothelial HIF-Prolyl hydroxylase 2 (PHD2) Induces Cardiac Hypertrophy and Fibrosis

BackgroundCardiac hypertrophy and fibrosis are common adaptive responses to injury and stress, eventually leading to heart failure. Hypoxia signaling is important to the (patho)physiological process of cardiac remodeling. However, the role of endothelial Prolyl-4 hydroxylase 2 (PHD2)/hypoxia inducible factors (HIFs) signaling in the pathogenesis of heart failure remains elusive. Methods and ResultsMice with Tie2-Cre-mediated deletion of Egln1 (encoding PHD2) (Egln1Tie2Cre) exhibited left ventricular (LV) hypertrophy evident by increased thickness of anterior and posterior wall and LV mass, as well as cardiac fibrosis. Tamoxifen-induced endothelial Egln1 deletion in adult mice also induced LV hypertrophy and fibrosis. Additionally, we observed a marked decrease of PHD2 expression in heart tissues and cardiovascular endothelial cells from patients with cardiomyopathy. Moreover, genetic ablation of Hif2a but not Hif1a in Egln1Tie2Cre mice normalized cardiac size and function. RNA sequencing analysis also demonstrated HIF-2 as a critical mediator of signaling related to cardiac hypertrophy and fibrosis. Pharmacological inhibition of HIF-2 attenuated cardiac hypertrophy and fibrosis in Egln1Tie2Cre mice. ConclusionsThe present studies define for the first time an unexpected role of endothelial PHD2 deficiency in inducing cardiac hypertrophy and fibrosis in a HIF-2 dependent manner. PHD2 was markedly decreased in cardiovascular endothelial cells in patients with cardiomyopathy. Thus, targeting PHD2/HIF-2 signaling may represent a novel therapeutic approach for the treatment of pathological cardiac hypertrophy and failure.

physiology↗

bioRxiv2021

Deconvolution of Expression for Nascent RNA Sequencing Data (DENR) Highlights Pre-RNA Isoform Diversity in Human Cells

Quantification of mature-RNA isoform abundance from RNA-seq data has been extensively studied, but much less attention has been devoted to quantifying the abundance of distinct precursor RNAs based on nascent RNA sequencing data. Here we address this problem with a new computational method called Deconvolution of Expression for Nascent RNA sequencing data (DENR). DENR models the nascent RNA read counts at each locus as a mixture of user-provided isoforms. The performance of the baseline algorithm is enhanced by the use of machine-learning predictions of transcription start sites (TSSs) and an adjustment for the typical "shape profile" of read counts along a transcription unit. We show using simulated data that DENR clearly outperforms simple read-count-based methods for estimating the abundances of both whole genes and isoforms. By applying DENR to previously published PRO-seq data from K562 and CD4+ T cells, we find that transcription of multiple isoforms per gene is widespread, and the dominant isoform frequently makes use of an internal TSS. We also identify > 200 genes whose dominant isoforms make use of different TSSs in these two cell types. Finally, we apply DENR and StringTie to newly generated PRO-seq and RNA-seq data, respectively, for human CD4+ T cells and CD14+ monocytes, and show that entropy at the pre-RNA level makes a disproportionate contribution to overall isoform diversity, especially across cell types. Altogether, DENR is the first computational tool to enable abundance quantification of pre-RNA isoforms based on nascent RNA sequencing data, and it reveals high levels of pre-RNA isoform diversity in human cells.

genomics↗

bioRxiv2021

DNA methylation clocks show slower progression of aging in naked mole-rat queens

Naked mole-rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity, and are seemingly resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we generated DNA methylation profiles from 329 tissues from animals of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40). We observed strong aging effects on NMR DNA methylation, from which we developed seven highly accurate age estimators (epigenetic clocks) for several tissues (pan-tissue, blood, kidney clock, liver clock, skin clock) and two dual species (human-NMR) clocks. By identifying age-related cytosine methylation that are shared between NMR and humans, but not with the mouse, we identified genes and cellular pathways that impinge on developmental and metabolic processes that are potentially involved in NMR and human longevity. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than non-breeders, a feature that is also observed in some eusocial insects. CpGs associated with queen status were located near developmental genes and those that are regulated by the LHX3 transcription factor that controls pituitary development. In summary, our study demonstrates that despite a phenotype of reduced senescence, the NMR ages epigenetically through developmental and metabolic processes, and that NMR queens age more slowly than non-breeders.

developmental biology↗

bioRxiv2021

Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

microbiology↗