A5041059730- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- interferon and immune responses
- Respiratory viral infections research
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- SARS-CoV-2 detection and testing
- Genetic and phenotypic traits in livestock
- Genetic Mapping and Diversity in Plants and Animals
- Long-Term Effects of COVID-19
- Cancer, Stress, Anesthesia, and Immune Response
- Vitamin C and Antioxidants Research
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- Viral Infections and Vectors
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- Viral Infections and Outbreaks Research
- Cytokine Signaling Pathways and Interactions
- COVID-19 epidemiological studies
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
University of North Carolina at Chapel Hill
2015-2024
Public Health Department
2014-2022
North Carolina Division of Public Health
2020
UNC Lineberger Comprehensive Cancer Center
2015
Oregon Medical Research Center
2014
Communities In Schools of Orange County
2014
University of Michigan
2006-2009
Regional West Medical Center
2006
The Wistar Institute
2002
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses in vitro vivo.
The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained previous outbreaks, perhaps world is better equipped to deal most recent emergent group 2B coronavirus.
The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2), a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack thorough understanding mechanisms humoral immunity SARS-CoV-24. Here analyse large panel human monoclonal antibodies that target spike (S) glycoprotein5, identify several exhibit potent neutralizing activity fully block receptor-binding...
The spike aspartic acid-614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. exhibits more efficient infection, replication, competitive fitness primary human airway epithelial cells maintains similar morphology vitro neutralization properties, compared with the ancestral...
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East (MERS)-CoV underscores the threat cross-species transmission events leading to outbreaks in humans. Here we examine disease potential a SARS-like virus, SHC014-CoV, which is currently circulating Chinese horseshoe bat populations. Using SARS-CoV reverse genetics system, generated characterized chimeric virus expressing spike SHC014 mouse-adapted backbone. results indicate that group 2b viruses encoding...
Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of acute coronavirus (SARS-CoV) infection. SARS-CoV emerged 2002 to 2003 and led a global outbreak SARS. As with the outcome human infection, intranasal infection C57BL/6J mice mouse-adapted results high-titer virus replication within lung, induction inflammatory cytokines chemokines, immune cell infiltration lung. Using this model, we investigated role complement system during We...
Coronaviruses are prone to transmission new host species, as recently demonstrated by the spread humans of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent disease 2019 (COVID-19) pandemic1. Small animal models that recapitulate SARS-CoV-2 needed urgently for rapid evaluation medical countermeasures2,3. cannot infect wild-type laboratory mice owing inefficient interactions between viral spike protein and mouse orthologue human receptor, angiotensin-converting...
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe structure-based design of self-assembling protein nanoparticle immunogens that elicit potent protective antibody responses against in mice. The vaccines display 60 spike receptor-binding domains (RBDs) a highly immunogenic array induce neutralizing titers 10-fold higher than prefusion-stabilized despite 5-fold lower dose. Antibodies elicited by RBD nanoparticles target multiple distinct...
ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that highly pathogenic in aged populations and maintained with great diversity zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy young-animal models against homologous viral strains, has not been thoroughly evaluated using variants replicate the end stage lung disease phenotypes seen during human epidemic. Using adjuvanted unadjuvanted double-inactivated SARS-CoV (DIV)...
Outbreaks from zoonotic sources represent a threat to both human disease as well the global economy. Despite wealth of metagenomics studies, methods leverage these datasets identify future threats are underdeveloped. In this study, we describe an approach that combines existing data with reverse genetics engineer reagents evaluate emergence and pathogenic potential circulating viruses. Focusing on severe acute respiratory syndrome (SARS)-like viruses, results indicate WIV1-coronavirus (CoV)...
The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that being developed as resource for mammalian systems genetics. Here we describe an experiment uses partially CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis incipient strains reveals high diversity, balanced allele frequencies, dense, evenly distributed recombination sites—all ideal qualities genetics We map discrete, complex, biomolecular traits contrast two...
Targeting sarbecoviruses As we continue to battle the COVID-19 pandemic, must confront possibility of new pathogenic coronaviruses emerging in humans future. With this mind, Rappazzo et al. isolated antibodies from a survivor 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), used yeast display libraries introduce diversity into these antibodies, and then screened for binding SARS-CoV-2. One affinity-matured progeny strongly neutralized SARS-CoV-2, SARS-CoV, two SARS-related...
A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as causative agent of a severe acute respiratory syndrome (SARS) resembling illness caused by SARS (SARS-CoV). Although derived from CoV family, two viruses are genetically distinct and do not use same receptor. Here, we investigated whether HCoV-EMC SARS-CoV induce similar or host responses after infection lung epithelial cell line. able to replicate efficiently Calu-3 cells similarly induced minimal...
The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis global response subsequent antagonism has yet be examined. Employing models human airway, transcriptomics proteomics datasets were used compare patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute syndrome...
Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach identify new network connections mediating acute lung injury, using severe respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized time course of matched virologic, pathological, transcriptomic data within...
Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the integrity laboratory stocks. We have developed third generation Mouse Universal Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array house mouse (Mus musculus). The bulk content GigaMUGA is optimized mapping in Collaborative Cross Diversity Outbred populations, substrain-level identification mice. In addition to 141,090 single nucleotide polymorphism probes,...
The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and, more recently, Middle Eastern CoV (MERS-CoV) underscores the importance understanding critical aspects infection and pathogenesis. Despite significant insights into cross-species transmission, replication, virus-host interactions, successful therapeutic options for CoVs do not yet exist. Recent identification SARS-CoV NSP16 as a viral 2'-O-methyltransferase (2'-O-MTase) led to possibility utilizing...
Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs ability infect humans without adaptation. These results suggested additional barriers limit zoonotic CoV. In this work, we describe overcoming host restriction two Middle East (MERS)-like bat using exogenous protease treatment. We found spike protein PDF2180-CoV,...