Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
1.
EBioMedicine ; 75: 103762, 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1587929

ABSTRACT

BACKGROUND: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. METHODS: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. FINDINGS: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. INTERPRETATION: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. FUNDING: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.

2.
Preprint | EuropePMC | ID: ppcovidwho-296804

ABSTRACT

The devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

3.
Clin Infect Dis ; 73(11): e4154-e4165, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1559099

ABSTRACT

BACKGROUND: Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren't well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. METHODS: We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. RESULTS: Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P < .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P < .025). CONCLUSIONS: Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.

4.
Emerg Microbes Infect ; : 1-34, 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1537457

ABSTRACT

The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378 T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.

5.
Front Med (Lausanne) ; 8: 701836, 2021.
Article in English | MEDLINE | ID: covidwho-1394782

ABSTRACT

Background: It is much valuable to evaluate the comparative effectiveness of the coronavirus disease 2019 (COVID-19) prevention and control in the non-pharmacological intervention phase of the pandemic across countries and identify useful experiences that could be generalized worldwide. Methods: In this study, we developed a susceptible-exposure-infectious-asymptomatic-removed (SEIAR) model to fit the daily reported COVID-19 cases in 160 countries. The time-varying reproduction number (R t ) that was estimated through fitting the mathematical model was adopted to quantify the transmissibility. We defined a synthetic index (I AC ) based on the value of R t to reflect the national capability to control COVID-19. Results: The goodness-of-fit tests showed that the SEIAR model fitted the data of the 160 countries well. At the beginning of the epidemic, the values of R t of countries in the European region were generally higher than those in other regions. Among the 160 countries included in the study, all European countries had the ability to control the COVID-19 epidemic. The Western Pacific Region did best in continuous control of the epidemic, with a total of 73.76% of countries that can continuously control the COVID-19 epidemic, while only 43.63% of the countries in the European Region continuously controlled the epidemic, followed by the Region of Americas with 52.53% of countries, the Southeast Asian Region with 48% of countries, the African Region with 46.81% of countries, and the Eastern Mediterranean Region with 40.48% of countries. Conclusion: Large variations in controlling the COVID-19 epidemic existed across countries. The world could benefit from the experience of some countries that demonstrated the highest containment capabilities.

6.
Nat Commun ; 12(1): 2790, 2021 05 13.
Article in English | MEDLINE | ID: covidwho-1387341

ABSTRACT

SARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.


Subject(s)
COVID-19/diagnosis , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Virus Replication/genetics , Animals , COVID-19/immunology , COVID-19/virology , Cell Line, Tumor , Chlorocebus aethiops , Cricetinae , Cytokines/immunology , Cytokines/metabolism , Female , Host-Pathogen Interactions , Humans , Male , Mesocricetus , Mice, Inbred BALB C , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vero Cells , Virulence/genetics , Virulence/immunology
7.
Nat Commun ; 12(1): 134, 2021 01 08.
Article in English | MEDLINE | ID: covidwho-1387323

ABSTRACT

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/transmission , Sialic Acids/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment , Animals , Caco-2 Cells , Cell Line, Tumor , Chlorocebus aethiops , Cricetinae , Furin/metabolism , HEK293 Cells , Heparitin Sulfate/metabolism , Humans , Intestinal Mucosa/metabolism , Intestines/virology , Lung/pathology , Lung/virology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/pathology , Vero Cells , Virus Internalization , Virus Replication/physiology
8.
Clin Infect Dis ; 73(2): e437-e444, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315658

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains the furin cleavage Proline-Arginine-Arginine-Alanine (PRRA) motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. Whether bat-like coronaviral variants without PRRA (∆PRRA) can establish natural infections in humans is unknown. METHODS: Here, we developed a duplex digital polymerase chain reaction assay to examine ∆PRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters, and coronavirus disease 2019 (COVID-19) patients. RESULTS: We found that SARS-CoV-2, as currently transmitting in humans, contained a quasispecies of wild-type, ∆PRRA variants and variants that have mutations upstream of the PRRA motif. Moreover, the ∆PRRA variants were readily detected despite being at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients, including in acute cases and a family cluster, with a prevalence rate of 52.9%. CONCLUSIONS: Our findings demonstrate that bat-like SARS-CoV-2ΔPRRA not only naturally exists but remains transmissible in COVID-19 patients, which has significant implications regarding the zoonotic origin and natural evolution of SARS-CoV-2.


Subject(s)
COVID-19 , Chiroptera , Alanine , Animals , Arginine , Humans , Proline , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
9.
Front Immunol ; 12: 697074, 2021.
Article in English | MEDLINE | ID: covidwho-1311376

ABSTRACT

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.


Subject(s)
Adenovirus Vaccines/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization Schedule , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Vaccination/methods , Adenovirus Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Disease Models, Animal , Female , HEK293 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Pan troglodytes , RNA, Viral/blood , Spike Glycoprotein, Coronavirus/immunology , Transfection , Treatment Outcome
10.
Nat Commun ; 12(1): 4210, 2021 07 09.
Article in English | MEDLINE | ID: covidwho-1303772

ABSTRACT

Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor angiotensin-converting enzyme-2 (ACE2) in binding to RBD. Site-directed mutagenesis confirms these common binding features although some minor differences are found. One representative antibody, P5A-3C8, demonstrates extraordinarily protective efficacy in a golden Syrian hamster model against SARS-CoV-2 infection. However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies. The discovery of public antibodies and shared escape mutation highlight the intricate relationship between antibody response and SARS-CoV-2, and provide critical reference for the development of antibody and vaccine strategies to overcome the antigenic variation of SARS-CoV-2.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Receptors, Virus/immunology , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Binding Sites/immunology , COVID-19/immunology , Cricetinae , Disease Models, Animal , Epitopes/immunology , Female , Humans , Male , Neutralization Tests , Receptors, Antigen, B-Cell/immunology , Spike Glycoprotein, Coronavirus/immunology
11.
Clin Infect Dis ; 72(10): e659-e662, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232198

ABSTRACT

We recently reported a patient with coronavirus disease 2019 reinfection. Here, we show that serum neutralizing antibodies could be detected during the first episode but not at the presentation of the second episode. During reinfection, neutralizing antibodies and high avidity immunoglobulin G were found within 8 days after hospitalization, whereas immunoglobulin M response was absent.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Immunoglobulin M , Reinfection , SARS-CoV-2
12.
Emerg Microbes Infect ; 10(1): 874-884, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1199439

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic is unlikely to abate until sufficient herd immunity is built up by either natural infection or vaccination. We previously identified ten linear immunodominant sites on the SARS-CoV-2 spike protein of which four are located within the RBD. Therefore, we designed two linkerimmunodominant site (LIS) vaccine candidates which are composed of four immunodominant sites within the RBD (RBD-ID) or all the 10 immunodominant sites within the whole spike (S-ID). They were administered by subcutaneous injection and were tested for immunogenicity and in vivo protective efficacy in a hamster model for COVID-19. We showed that the S-ID vaccine induced significantly better neutralizing antibody response than RBD-ID and alum control. As expected, hamsters vaccinated by S-ID had significantly less body weight loss, lung viral load, and histopathological changes of pneumonia. The S-ID has the potential to be an effective vaccine for protection against COVID-19.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunodominant Epitopes/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Cricetinae , Female , HEK293 Cells , Humans , Male , Mesocricetus , Mice , Mice, Inbred BALB C , Vaccination
13.
Cell ; 184(8): 2212-2228.e12, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1116430

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line-HK-2-that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Host Microbial Interactions/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vasopressins/immunology , Virus Internalization , COVID-19/immunology , COVID-19/virology , Cell Line , Humans , Protein Binding
14.
Cell Host Microbe ; 29(4): 551-563.e5, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1101147

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC50 range, 0.0007-0.35 µg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection, and vaccine.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , SARS-CoV-2/immunology , Turbinates/virology , Angiotensin-Converting Enzyme 2/physiology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , Cricetinae , Female , HEK293 Cells , Humans , Male , Mesocricetus , Viral Load
15.
Medicine (Baltimore) ; 100(1): e24108, 2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1024160

ABSTRACT

BACKGROUND: This meta-analysis aimed to compare the clinical symptoms of COVID-19 pneumonia in children. METHODS AND ANALYSIS: Electronic databases including PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI) database, Wanfang Database, and Chinese Biomedical Literature Database (CBM) were searched from its inception to June 21, 2020. We only included studies that reported clinical symptoms of COVID pneumonia in children. Quality of the included studies was assessed by 2 authors. Pooled results were summarized by STATA 12.0 software.The heterogeneity was measured by I2 tests (I2 < 50 indicates little heterogeneity, I2≥50 indicates high heterogeneity). Publication bias was performed by funnel plot and statistically assessed by Begg test (P > .05 as no publication bias). RESULTS: Results will be shown as figures or tables. CONCLUSION: Our study aims to systematically present the clinical symptoms of COVID-19 pneumonia patients in children, so as to further provide guidance for clinical management.


Subject(s)
COVID-19/diagnosis , Pneumonia, Viral/diagnosis , Research Design , Child , Humans , Meta-Analysis as Topic , Pneumonia, Viral/virology , SARS-CoV-2 , Systematic Reviews as Topic
16.
Theranostics ; 11(5): 2170-2181, 2021.
Article in English | MEDLINE | ID: covidwho-1016389

ABSTRACT

Introduction: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin-converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 15, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children's lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Results: It revealed that infants (< 1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (> 1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children's lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants' lungs. The ACE2+SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Conclusions: Infants (< 1 yrs.-old) with SARS-CoV-2 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , Lung/cytology , Stem Cells/metabolism , Adolescent , Biopsy , Child , Child, Preschool , Female , Humans , Immune System , Infant , Infant, Newborn , Lung/virology , Male , RNA-Seq , Risk Factors , SARS-CoV-2 , SOX9 Transcription Factor/metabolism , Single-Cell Analysis , Stem Cells/virology
SELECTION OF CITATIONS
SEARCH DETAIL
...