A5063843267- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Virus-based gene therapy research
- Genomics and Phylogenetic Studies
- Rabies epidemiology and control
- SARS-CoV-2 detection and testing
- Advanced biosensing and bioanalysis techniques
- Cytomegalovirus and herpesvirus research
- Long-Term Effects of COVID-19
- Bacterial Genetics and Biotechnology
- Legionella and Acanthamoeba research
- Bacillus and Francisella bacterial research
- Complement system in diseases
- Herpesvirus Infections and Treatments
- Biochemical and Structural Characterization
- Virology and Viral Diseases
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- RNA Research and Splicing
The University of Texas at Austin
2018-2024
Mount Royal University
2024
Novartis (United States)
2019
Lawrence Berkeley National Laboratory
2003-2017
Joint Genome Institute
2014-2017
MindSpec
2011
Duke University Hospital
2010
Duke Medical Center
2010
Duke University
2010
Stabilizing the prefusion SARS-CoV-2 spike The development of therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on (S) protein that decorates viral surface. A version ectodomain includes two proline substitutions (S-2P) stabilizes conformation has been used to determine high-resolution structures. However, even S-2P unstable difficult produce in mammalian cells. Hsieh et al. characterized many individual combined...
Seeking broad protection As scientists develop therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the risk of emergent coronaviruses makes it important to also identify broadly protective antibodies. Wec et al. isolated characterized hundreds viral spike protein SARS-CoV-2 from memory B cells a survivor 2003 outbreak caused by related coronavirus, SARS-CoV. In both these viruses, facilitated entry binding angiotensin-converting enzyme...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies key class of therapeutics that may bridge widespread vaccination campaigns offer treatment solution in populations less responsive to vaccination. Here, we report high-throughput microfluidic screening antigen-specific B cells led the identification LY-CoV555 (also known as bamlanivimab), potent anti-spike...
To investigate the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immune population, we coincupi bated authentic virus with a highly neutralizing plasma from COVID-19 convalescent patient. The fully neutralized for seven passages, but, after 45 d, deletion F140 spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution receptor-binding (RBD) occurred, followed, at 80, by insertion NTD N5 containing new glycan sequon,...
ABSTRACT To investigate the evolution of SARS-CoV-2 in immune population, we co-incubated authentic virus with a highly neutralizing plasma from COVID-19 convalescent patient. The fully neutralized for 7 passages, but after 45 days, deletion F140 spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution receptor-binding (RBD) occurred, followed at 80 by insertion NTD N5 containing new glycan sequon, which generated variant completely resistant...
The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unknown. Proteomic deconvolution IgG repertoire to spike glycoprotein convalescent subjects revealed response is directed predominantly (>80%) against residing outside receptor domain (RBD). In one subject, just four lineages accounted for 93.5% response, including an amino (N)-terminal...
SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification LY-CoV555, potent anti-spike neutralizing antibody from convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding receptor-binding domain, ACE2 inhibition, activity. In rhesus macaque challenge model, prophylaxis doses as low 2.5...
ABSTRACT The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts develop therapeutics, diagnostics, and vaccines mitigate this public health emergency. A key target of these is spike (S) protein, a large trimeric class I fusion protein that metastable difficult produce recombinantly in quantities. Here, we designed expressed over 100 structure-guided variants based upon previously determined cryo-EM structure prefusion spike. Biochemical, biophysical...
SUMMARY Although humoral immunity is essential for control of SARS-CoV-2, the molecular composition, binding epitopes and effector functions immunoglobulin G (IgG) antibodies that circulate in blood plasma following infection are unknown. Proteomic deconvolution circulating IgG repertoire (Ig-Seq 1 ) to spike ectodomain (S-ECD 2 four convalescent study subjects revealed response oligoclonal directed predominantly (>80%) S-ECD lie outside receptor domain (RBD). When comparing either RBD,...
Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared C57BL/6J, the specific genes responsible for this differential phenotype unknown. Using chromosome substitution strains (CSS), we found loci on chromosomes 8, 11, and 18 influence susceptibility S. in mice. We then used two candidate gene selection strategies identify these three associated with susceptibility, targeted identified by both strategies. First, whole genome...
Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire convalescent SARS donor identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on spike (S) protein. A large proportion display high levels somatic hypermutation cross-react with...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge the clinical treatment disease (COVID-19). Therefore, need for ongoing discovery efforts identify broadly reactive monoclonal antibodies SARS-CoV-2 is utmost importance. Here, we report panel isolated using linking B cell receptor antigen specificity through sequencing (LIBRA-seq) technology...
Abstract Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no has been FDA-approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize in its metastable prefusion conformation. One variant two engineered interprotomer disulfide bonds cavity-filling (gB-C7), displayed increased expression...
The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. RV3 fusion (F) protein is inherently metastable will likely require prefusion (preF) stabilization vaccine effectiveness. Here we used structure-based design to...
Human cytomegalovirus (HCMV) glycoprotein B (gB) is a class III membrane fusion protein required for viral entry. HCMV vaccine candidates containing gB have demonstrated moderate clinical efficacy, but no has been approved. Here, we used structure-based design to identify and characterize amino acid substitutions that stabilize in its metastable prefusion conformation. One variant two engineered interprotomer disulfide bonds cavity-filling (gB-C7), displayed increased expression...
RNA-sequencing (RNA-seq) enables in-depth exploration of transcriptomes, but typical sequencing depth often limits its comprehensiveness. In this study, we generated nearly 3 billion RNA-Seq reads, totaling 341 Gb sequence, from a Zea mays seedling sample. At depth, near complete snapshot the transcriptome was observed consisting over 90% annotated transcripts, including lowly expressed transcription factors. A novel hybrid strategy combining de novo and reference-based assemblies yielded...
Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of highlights need for pan-coronavirus interventions effective pandemic preparedness. Here, using LIBRA-seq, we report a panel 50 coronavirus antibodies isolated B cells. Of these antibodies, 54043-5 was shown to bind S2 subunit spike proteins alpha-, beta-, deltacoronaviruses. A cryo-EM structure bound pre-fusion SARS-CoV-2 defined an...
Molecular underpinnings of complex psychiatric disorders such as autism spectrum (ASD) remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated ASD, expanding the search space for its disease etiology. We exploited high genetic heterogeneity ASD to derive a predictive map candidate genes by an integrated bioinformatics approach. Using reference set 84 Rare and Syndromic (AutRef84), we built composite profile based on both functional...