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1.
Theranostics ; 10(19): 8818-8820, 2020.
Article in English | MEDLINE | ID: mdl-32754280

ABSTRACT

[This corrects the article DOI: 10.7150/thno.27882.].

2.
Mol Ther Nucleic Acids ; 21: 577-591, 2020 Jun 27.
Article in English | MEDLINE | ID: mdl-32721878

ABSTRACT

Circular RNAs (circRNAs) play an essential regulatory role in multiple cancers. However, the role of a large number of circRNAs in gastric cancer (GC) is still unknown. Here, hsa_circ_0139996 (circREPS2), a novel circRNA that was significantly downregulated in GC, was selected for further investigation. circREPS2 was validated and analyzed by DNA sequencing and quantitative real-time PCR. The roles of circREPS2 in GC cells were verified by gain- and loss-of-function experiments. Bioinformatics analysis, luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays were performed to evaluate the functional mechanism of circREPS2 on microRNA-558 (miR-558)/RUNX3/ß-catenin axis in GC cells. In the present study, we found that circREPS2 was downregulated in GC tissues and cell lines. Low expression of circREPS2 was associated with a higher tumor-node-metastasis (TNM) stage, poor tumor differentiation, and larger tumor size in GC patients. Functionally, circREPS2 significantly inhibited GC cell proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) in vitro and tumorigenesis in vivo. Furthermore, our data demonstrated that circREPS2 acted as a miR-558 sponge and upregulated RUNX3 expression to inactivate ß-catenin signaling in GC cells. In conclusion, circREPS2 suppresses the progression of GC via miR-558/RUNX3/ß-catenin signaling and is a novel promising biomarker and target for GC treatment.

3.
Allergy ; 2020 Jul 27.
Article in English | MEDLINE | ID: mdl-32716553

ABSTRACT

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < 0.01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = 0.025) than asthmatics. COPD patients, particular those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells, and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8 and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated but TNF-α, IL-12 and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

4.
Cell Death Dis ; 11(7): 567, 2020 Jul 23.
Article in English | MEDLINE | ID: mdl-32703937

ABSTRACT

Surgical decompression after spinal cord injury (SCI) is a conventional treatment. Although it has been proven to have clinical effects, there are certain limitations, such as the surgical conditions that must be met and the invasive nature of the treatment. Therefore, there is an urgent need to develop a simple and maneuverable therapy for the emergency treatment of patients with SCI before surgery. Rapamycin (RAPA) has been reported to have potential as a therapeutic agent for SCI. In this study, we observed the therapeutic effects of rapamycin and surgical decompression, in combination or separately, on the histopathology in rabbits with SCI. After combination therapy, intramedullary pressure (IMP) decreased significantly, autophagic flux increased, and apoptosis and demyelination were significantly reduced. Compared with RAPA/surgical decompression alone, the combination therapy had a significantly better effect. In addition, we evaluated the effects of mechanical pressure on autophagy after SCI by assessing changes in autophagic initiation, degradation, and flux. Increased IMP after SCI inhibited autophagic degradation and impaired autophagic flux. Decompression improved autophagic flux after SCI. Our findings provide novel evidence of a promising strategy for the treatment of SCI in the future. The combination therapy may effectively improve emergency treatment after SCI and promote the therapeutic effect of decompression. This study also contributes to a better understanding of the effects of mechanical pressure on autophagy after neurotrauma.

5.
Cell ; 2020 Jun 28.
Article in English | MEDLINE | ID: mdl-32645327

ABSTRACT

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

7.
Science ; 2020 Jul 02.
Article in English | MEDLINE | ID: mdl-32616673

ABSTRACT

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.

8.
Sci Rep ; 10(1): 10302, 2020 Jun 25.
Article in English | MEDLINE | ID: mdl-32587321

ABSTRACT

The genera Kernia and Acaulium comprise species commonly isolated from dung, soil, decaying meat and skin of animal. The taxonomy of these fungi has been controversial and relies mainly on morphological criteria. With the aim to clarify the taxonomy and phylogeny of these fungi, we studied all the available ex-type strains of a large set of species by means of morphological and molecular phylogenetic analyses. Phylogenetic analysis of the partial internal transcribed spacer region (ITS) and the partial 28S rDNA (LSU) showed that the genera Kernia and Acaulium were found to be separated in two distinct lineages in Microascaceae. Based on morphological characters and multilocus phylogenetic analysis of the ITS, LSU, translation elongation factor 1α and ß-tubulin genes, the species in Kernia and Acaulium were well separated and two new combinations are introduced, i.e. Acaulium peruvianum and Acaulium retardatum, a new species of Kernia is described, namely Kernia anthracina. Descriptions of the phenotypic features and molecular phylogeny for identification are discussed for accepted species in two genera in this study.

9.
Virol J ; 17(1): 83, 2020 Jun 24.
Article in English | MEDLINE | ID: mdl-32580773

ABSTRACT

An amendment to this paper has been published and can be accessed via the original article.

10.
Sci Rep ; 10(1): 10401, 2020 Jun 23.
Article in English | MEDLINE | ID: mdl-32576881

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

11.
Ying Yong Sheng Tai Xue Bao ; 31(4): 1357-1364, 2020 Apr.
Article in Chinese | MEDLINE | ID: mdl-32530212

ABSTRACT

Mytilopsis sallei, an invasive alien species, has strong reproductive ability and high adaptability. It can severely endanger biodiversity of intertidal ecosystem after invasion. The intertidal zones and oyster breeding areas in some coastal areas of Guangdong Province have been severely invaded by M. sallei. To examine the potential habitat of M. sallei in China, we established a potential habitat prediction model of M. sallei using Maxent and ArcGIS method for China and global scales. The model was verified by the method of receiver operating characteristic curve (ROC) analysis and field investigation. The results showed that M. sallei could distribute with high probabili-ty in the area between North and South America, South India in Asia, Sri Lanka, the south coast of the Yangtze River in China, and in Van Dimen Bay of the southern hemisphere. In China, M. sallei mainly distributed in coastal provinces south of Shanghai. The main environmental factors affecting the suitable distribution areas for M. sallei were water vapor pressure, temperature, and solar radiation. After ROC detection, the AUC values of both the training and testing sets were 0.996, indicating that the prediction reached an excellent level. Our results provide theoretical basis for the risk assessment and management of M. sallei, and complement the potential habitat prediction of invasive species in China.


Subject(s)
Bivalvia , Ecosystem , Animals , Asia , China , Introduced Species
12.
Vaccine ; 38(31): 4783-4791, 2020 06 26.
Article in English | MEDLINE | ID: mdl-32507409

ABSTRACT

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of "disease enhancement" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.


Subject(s)
Antibodies, Viral/adverse effects , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Viral Vaccines/adverse effects , Viral Vaccines/immunology , Animals , Betacoronavirus/pathogenicity , Clinical Trials as Topic , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Disease Models, Animal , Humans , Pandemics , Pneumonia, Viral/virology , Risk Assessment , Severe Acute Respiratory Syndrome/immunology
13.
Front Cell Infect Microbiol ; 10: 219, 2020.
Article in English | MEDLINE | ID: mdl-32500039

ABSTRACT

Mycobacterium tuberculosis clinical strains usually possess traits different from the laboratory strains like H37Rv, especially those clinical drug resistant strains. With whole genome and transcriptome sequencing, we depicted the feature of two multi-drug resistant Mtb strains in resistance and virulence. Compared with H37Rv, the differential expressed genes (DEGs) of the MDR strains showed featured enrichment in arginine biosynthesis, fatty acid biosynthesis, and metabolism pathway. In the subset of virulence genes, the overlapping DEGs of the MDR strains exhibited downregulation of the cluster in type VII secretion system. In the mice experiment, the MDR strains showed attenuated but distinct virulence, both in survival rate and pathology. Taken together, the whole genome and transcriptome analysis could help understand the unique feature of the MDR strains both in resistance and virulence.

14.
Sci Transl Med ; 12(546)2020 Jun 03.
Article in English | MEDLINE | ID: mdl-32493792

ABSTRACT

HIV-associated morbidity and mortality have markedly declined because of combinational antiretroviral therapy, but HIV readily mutates to develop drug resistance. Developing antivirals against previously undefined targets is essential to treat existing drug-resistant HIV strains. Some peptides derived from HIV-1 envelope glycoprotein (Env, gp120-gp41) have been shown to be effective in inhibiting HIV-1 infection. Therefore, we screened a peptide library from HIV-1 Env and identified a peptide from the cytoplasmic region, designated F9170, able to effectively inactivate HIV-1 virions and induce necrosis of HIV-1-infected cells, and reactivated latently infected cells. F9170 specifically targeted the conserved cytoplasmic tail of HIV-1 Env and effectively disrupted the integrity of the viral membrane. Short-term monoadministration of F9170 controlled viral loads to below the limit of detection in chronically SHIV-infected macaques. F9170 can enter the brain and lymph nodes, anatomic reservoirs for HIV latency. Therefore, F9170 shows promise as a drug candidate for HIV treatment.

15.
Stroke ; 51(7): 2219-2223, 2020 07.
Article in English | MEDLINE | ID: mdl-32466735

ABSTRACT

BACKGROUND AND PURPOSE: Information on stroke survivors infected with coronavirus disease 2019 (COVID-19) is limited. The aim of this study was to describe specific clinical characteristics and outcomes of patients with COVID-19 with a history of stroke. METHODS: All the confirmed cases of COVID-19 at Tongji Hospital from January 27 to March 5, 2020, were included in our cohort study. Clinical data were analyzed and compared between patients with and without a history of stroke. RESULTS: Of the included 1875 patients with COVID-19, 50 patients had a history of stroke. The COVID-19 patients with medical history of stroke were older with more comorbidities, had higher neutrophil count, and lower lymphocyte and platelet counts than those without history of stroke. The levels of D-dimers, cardiac troponin I, NT pro-brain natriuretic peptide, and interleukin-6 were also markedly higher in patients with history of stroke. Stroke survivors who underwent COVID-19 developed more acute respiratory distress syndrome and received more noninvasive mechanical ventilation. Data from propensity-matched analysis indicated a higher proportion of patients with COVD-19 with a history of stroke were admitted to the intensive care unit requiring mechanical ventilation and were more likely to be held in the unit or die, compared with non-stroke history COVID-19 patients. CONCLUSIONS: Patients with COVID-19 with a history of stroke had more severe clinical symptoms and poorer outcomes compared with those without a history of stroke.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Stroke/epidemiology , Aged , Blood Cell Count , China/epidemiology , Comorbidity , Coronavirus Infections/epidemiology , Female , Hospital Mortality , Hospitals, University/statistics & numerical data , Humans , Male , Middle Aged , Pneumonia, Viral/epidemiology , Procedures and Techniques Utilization , Propensity Score , Recurrence , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome, Adult/etiology , Respiratory Distress Syndrome, Adult/therapy , Stroke/blood , Stroke/therapy , Treatment Outcome
16.
Transl Neurodegener ; 9(1): 20, 2020 May 27.
Article in English | MEDLINE | ID: mdl-32460886

ABSTRACT

BACKGROUND: Alzheimer's disease is a neurodegenerative disorder. Therapeutically, a transplantation of bone marrow mesenchymal stem cells (BMMSCs) can play a beneficial role in animal models of Alzheimer's disease. However, the relevant mechanism remains to be fully elucidated. MAIN BODY: Subsequent to the transplantation of BMMSCs, memory loss and cognitive impairment were significantly improved in animal models with Alzheimer's disease (AD). Potential mechanisms involved neurogenesis, apoptosis, angiogenesis, inflammation, immunomodulation, etc. The above mechanisms might play different roles at certain stages. It was revealed that the transplantation of BMMSCs could alter some gene levels. Moreover, the differential expression of representative genes was responsible for neuropathological phenotypes in Alzheimer's disease, which could be used to construct gene-specific patterns. CONCLUSIONS: Multiple signal pathways involve therapeutic mechanisms by which the transplantation of BMMSCs improves cognitive and behavioral deficits in AD models. Gene expression profile can be utilized to establish statistical regression model for the evaluation of therapeutic effect. The transplantation of autologous BMMSCs maybe a prospective therapy for patients with Alzheimer's disease.

17.
J Infect Dis ; 222(4): 551-555, 2020 07 23.
Article in English | MEDLINE | ID: mdl-32444876

ABSTRACT

We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations.


Subject(s)
Betacoronavirus , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Aerosols , Anal Canal/virology , Animals , Antibodies, Viral/blood , Betacoronavirus/genetics , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Chlorocebus aethiops , Female , Humans , Immunoglobulin G/blood , Lung/pathology , Lung/virology , Male , Mice , Mice, Transgenic , Pandemics , Peptidyl-Dipeptidase A/genetics , Pharynx/virology , RNA, Viral/isolation & purification , Respiratory System/virology , Risk , Specific Pathogen-Free Organisms , Time Factors , Vero Cells , Viral Load , Weight Loss
18.
JAMA Netw Open ; 3(5): e209666, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32437575

ABSTRACT

Importance: Health care workers (HCWs) have high infection risk owing to treating patients with coronavirus disease 2019 (COVID-19). However, research on their infection risk and clinical characteristics is limited. Objectives: To explore infection risk and clinical characteristics of HCWs with COVID-19 and to discuss possible prevention measures. Design, Setting, and Participants: This single-center case series included 9684 HCWs in Tongji Hospital, Wuhan, China. Data were collected from January 1 to February 9, 2020. Exposures: Confirmed COVID-19. Main Outcomes and Measures: Exposure, epidemiological, and demographic information was collected by a structured questionnaire. Clinical, laboratory, and radiologic information was collected from electronic medical records. A total of 335 medical staff were randomly sampled to estimate the prevalence of subclinical infection among a high-risk, asymptomatic population. Samples from surfaces in health care settings were also collected. Results: Overall, 110 of 9684 HCWs in Tongji Hospital tested positive for COVID-19, with an infection rate of 1.1%. Of them, 70 (71.8%) were women, and they had a median (interquartile range) age of 36.5 (30.0-47.0) years. Seventeen (15.5%) worked in fever clinics or wards, indicating an infection rate of 0.5% (17 of 3110) among first-line HCWs. A total of 93 of 6574 non-first-line HCWs (1.4%) were infected. Non-first-line nurses younger than 45 years were more likely to be infected compared with first-line physicians aged 45 years or older (incident rate ratio, 16.1; 95% CI, 7.1-36.3; P < .001). The prevalence of subclinical infection was 0.74% (1 of 135) among asymptomatic first-line HCWs and 1.0% (2 of 200) among non-first-line HCWs. No environmental surfaces tested positive. Overall, 93 of 110 HCWs (84.5%) with COVID-19 had nonsevere disease, while 1 (0.9%) died. The 5 most common symptoms were fever (67 [60.9%]), myalgia or fatigue (66 [60.0%]), cough (62 [56.4%]), sore throat (55 [50.0%]), and muscle ache (50 [45.5%]). Contact with indexed patients (65 [59.1%]) and colleagues with infection (12 [10.9%]) as well as community-acquired infection (14 [12.7%]) were the main routes of exposure for HCWs. Conclusions and Relevance: In this case series, most infections among HCWs occurred during the early stage of disease outbreak. That non-first-line HCWs had a higher infection rate than first-line HCWs differed from observation of previous viral disease epidemics. Rapid identification of staff with potential infection and routine screening among asymptomatic staff could help protect HCWs.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cross Infection/epidemiology , Cross Infection/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Adult , China/epidemiology , Coronavirus Infections/diagnosis , Cross Infection/prevention & control , Female , Health Personnel , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Risk Factors , Surveys and Questionnaires , Tertiary Care Centers , Young Adult
19.
Nat Commun ; 11(1): 2601, 2020 05 20.
Article in English | MEDLINE | ID: mdl-32433465

ABSTRACT

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.


Subject(s)
Antigens, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Antigens, Viral/chemistry , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Epitope Mapping , Guinea Pigs , Immunity, Humoral , Immunoglobulin G/immunology , Lung/immunology , Mice , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus , Models, Animal , Peptidyl-Dipeptidase A/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Viral Vaccines/chemistry
20.
Cell ; 182(1): 73-84.e16, 2020 07 09.
Article in English | MEDLINE | ID: mdl-32425270

ABSTRACT

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 Å cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody's epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.


Subject(s)
Antibodies, Monoclonal/isolation & purification , Antibodies, Neutralizing/isolation & purification , B-Lymphocytes/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Single-Cell Analysis , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/metabolism , Convalescence , High-Throughput Nucleotide Sequencing , Humans , Mice , Pandemics , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , VDJ Exons
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