A5049080246- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- RNA modifications and cancer
- Respiratory viral infections research
- CRISPR and Genetic Engineering
- interferon and immune responses
- Immune Cell Function and Interaction
- Plant Virus Research Studies
- Inflammasome and immune disorders
- RNA Research and Splicing
Novartis (United States)
2024
Washington University in St. Louis
2019-2022
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive infection despite complete absence angiotensin-converting enzyme (ACE2) expression. Remarkably, requires the E484D S variant; viruses expressing wild-type are not infectious. Anti-S monoclonal antibodies...
HIV-1 has high mutation rates and exists as mutant swarms within the host. Rapid evolution of allows virus to outpace host immune system, leading viral persistence. Approaches targeting immutable components are needed clear infection. Here, we report that caspase recruitment domain-containing protein 8 (CARD8) inflammasome senses protease activity. can evade CARD8 sensing because its remains inactive in infected cells before budding. Premature intracellular activation triggered...
Small-molecule targeting of RNA stem loops in 5′-end SARS-CoV-2 reveals novel targets for viral inhibition.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of disease 2019 (COVID-19) pandemic, is continuing to cause immense and social economic disruptions. Conventional assays that monitor SARS-CoV-2 growth in cell culture rely on costly time-consuming RNA extraction procedures, hampering progress basic research development effective therapeutics. Here, we developed a simple quantitative real-time PCR assay supernatants does not necessitate as accurate sensitive...
ABSTRACT Established in vitro models for SARS-CoV-2 infection are limited and include cell lines of non-human origin those engineered to overexpress ACE2, the cognate host receptor. We identified human H522 lung adenocarcinoma cells as naturally permissive despite complete absence ACE2. Infection required spike protein, though contrast ACE2-dependent models, alone was not sufficient infection. Temporally resolved transcriptomic proteomic profiling revealed alterations cycle antiviral...
In addition to its catalytic function, HIV-1 integrase (IN) binds the viral RNA genome (gRNA) through positively charged residues (i.e., R262, R263, R269, K273) within C-terminal domain (CTD) and regulates proper virion maturation. Mutation of these results in formation morphologically aberrant viruses blocked at an early reverse transcription stage cells.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of ongoing COVID-19 pandemic, has infected millions within just a few months and is continuing to spread around globe causing immense disease mortality. Assays monitor SARS-CoV-2 growth depend on time-consuming costly RNA extraction steps, hampering progress in basic research drug development efforts. Here we developed facile Q-RT-PCR assay that bypasses viral steps can replication kinetics from small amount...
The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects virus replication serve as leads for antiviral therapeutic development. RNA-biased amiloride scaffold was recently tuned target a viral RNA structure critical translation in enterovirus 71, ultimately uncovering mechanism modulate positive-sense replication. Analysis CoV genomes many...
ABSTRACT HIV-1 integrase (IN) has a non-catalytic function in virion maturation through its binding to the viral RNA genome (gRNA). Allosteric inhibitors (ALLINIs) and class II IN substitutions inhibit IN-gRNA result non-infectious viruses marked by mislocalization of gRNA within virions. utilizes basic residues C-terminal domain (CTD) bind gRNA. However, molecular nature how these mediate whether other regions are involved remain unknown. To address this, we have isolated compensatory...