A5010183731- SARS-CoV-2 and COVID-19 Research
- Influenza Virus Research Studies
- Respiratory viral infections research
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Endoplasmic Reticulum Stress and Disease
- Animal Virus Infections Studies
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- bioluminescence and chemiluminescence research
- Plant Virus Research Studies
- Brucella: diagnosis, epidemiology, treatment
- Diagnosis and treatment of tuberculosis
- Cytokine Signaling Pathways and Interactions
- Bacteriophages and microbial interactions
- COVID-19 Clinical Research Studies
- 3D Printing in Biomedical Research
- Enzyme Structure and Function
- Drug Transport and Resistance Mechanisms
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Congenital Diaphragmatic Hernia Studies
- Neonatal Respiratory Health Research
- Escherichia coli research studies
Duke University
2017-2025
Kettering University
2014
University of Chicago
2012
Highlights•CRISPR activation used in a genome-wide screen for viral restriction factors•B4GALNT2 was the major hit screen, and restricted IAV infection•B4GALNT2 modifies glycans containing α2,3-linked sialic acids•Glycan modification by B4GALNT2 infection all tested avian strainsSummaryInfluenza A virus (IAV) is pathogen that poses significant risks to human health. It therefore critical develop strategies prevent influenza disease. Many loss-of-function screens have been performed identify...
The COVID-19 pandemic has already led to more than 700,000 deaths and innumerable changes daily life worldwide. Along with development of a vaccine, identification effective antivirals treat infected patients is the highest importance. However, rapid drug discovery requires efficient methods identify novel compounds that can inhibit virus. In this work, we present method for identifying inhibitors SARS-CoV-2 main protease, 3CL pro . This reporter-based assay allows antiviral screening in...
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or experience breakthrough infections. Understanding common host factors necessary for life cycles of may reveal conserved therapeutic targets. Here, we used known substrate specificities mammalian protein kinases to deconvolute...
ABSTRACT While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies treat patients who become infected. Pharmacological targeting of a host factor required viral replication can suppress spread with low probability mutation leading resistance. In particular, kinases highly druggable targets and number conserved coronavirus proteins, notably the nucleoprotein (N), require phosphorylation full functionality. order understand how could be used...
Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that virus must co-opt complete its replication cycle. However, detailed understanding interactions between and cell necessary order facilitate development host-directed therapeutics. As first step, we performed genome-wide loss function screen using alphacoronavirus HCoV-229E better...
Influenza virus vaccine production is currently limited by the ability to grow circulating human strains in chicken eggs or cell culture. To facilitate cost-effective growth, are serially passaged under conditions, which frequently results mutations of major antigenic protein, viral hemagglutinin (HA). Human vaccination with an antigenically drifted strain known contribute poor efficacy. address this problem, we developed a replication-competent influenza A (IAV) artificial genomic...
Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and longevity of protection remains unclear. Postimmunization boosting has beneficial for disease protection, as new continue emerge, periodic (and perhaps annual) vaccination will likely recommended. New seasonal influenza virus vaccines currently need developed every year due continual antigenic drift, an undertaking made possible by a robust global vaccine production...
ABSTRACT Coronaviruses (CoVs) encode non-structural proteins (nsp’s) 1–16, which assemble to form replication-transcription complexes that function in viral RNA synthesis. All CoVs a proofreading 3′−5′ exoribonuclease protein 14 (nsp14-ExoN) mediates and high-fidelity replication is critical for other roles pathogenesis. The vitro enzymatic activity of nsp14-ExoN enhanced the presence cofactor nsp10. We introduced alanine substitutions nsp14 murine hepatitis virus (MHV) at nsp14-nsp10...
ABSTRACT Seasonal influenza vaccines provide mostly strain-specific protection due to the elicitation of antibody responses focused on evolutionarily plastic antigenic sites in hemagglutinin head domain. To direct humoral response toward more conserved epitopes, we generated an virus particle where full-length protein was replaced with a membrane-anchored, “headless” variant while retaining normal complement other viral structural proteins such as neuraminidase well RNAs. We found that...
ABSTRACT Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including M. , require DNA repair systems damage inflicted by during infection, but role double-strand break (DSB) is unclear. Double-strand breaks are most cytotoxic form must be repaired for chromosome...
Abstract The type I interferon (IFN) response is an important component of the innate immune to viral infection. Precise control responses critical; insufficient levels interferon-stimulated genes (ISGs) can lead a failure restrict spread while excessive ISG activation result in interferon-related pathologies. While both positive and negative regulatory factors magnitude duration IFN signaling, it also appreciated that number ISGs regulate aspects themselves. However, mechanisms underlying...
ABSTRACT In late 2019 a human coronavirus, now known as SARS-CoV-2, emerged, likely from zoonotic reservoir. This virus causes COVID-19 disease, has infected millions of people, and led to hundreds thousands deaths across the globe. While best interventions control ultimately stop pandemic are prophylactic vaccines, antiviral therapeutics important limit morbidity mortality in those already infected. At this time, only one FDA approved anti-SARS-CoV-2 drug, remdesivir, is available...
ABSTRACT Multiple coronaviruses (CoVs) can cause respiratory diseases in humans. While prophylactic vaccines designed to prevent infection are available for severe acute syndrome coronavirus-2 (SARS-CoV-2), incomplete vaccine efficacy, hesitancy, and the threat of other pathogenic CoVs which do not exist have highlighted need effective antiviral therapies. compounds targeting viral polymerase protease already clinical use, their sensitivity potential resistance mutations as well breadth...
Coronaviruses (CoVs) encode nonstructural proteins (nsps) 1-16, which assemble to form replication-transcription complexes that function in viral RNA synthesis. All CoVs a proofreading 3'-5' exoribonuclease (ExoN) nsp14 (nsp14-ExoN) mediates and high-fidelity replication is critical for other roles pathogenesis. The
Abstract Vaccines targeting SARS-CoV-2 have gained emergency FDA approval, however the breadth against emerging variants and longevity of protection remains unknown. Post-immunization boosting may be required, perhaps on an annual basis if virus becomes endemic pathogen. Seasonal influenza vaccines are already developed every year, undertaking made possible by a robust global vaccine production distribution infrastructure. To create seasonal combination viruses that is also amenable to...
Influenza virus vaccines currently afford short-term protection from viruses that are closely related to the vaccine strains. There is much effort develop improved, next-generation influenza elicit broader and longer-lasting protection.