Briana L. McGovern
A5005522829- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- SARS-CoV-2 detection and testing
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- COVID-19 epidemiological studies
- Viral Infections and Immunology Research
- Influenza Virus Research Studies
- Computational Drug Discovery Methods
- Bacteriophages and microbial interactions
- vaccines and immunoinformatics approaches
- COVID-19 and healthcare impacts
- Transgenic Plants and Applications
- Immunodeficiency and Autoimmune Disorders
- Infection Control and Ventilation
- Cancer therapeutics and mechanisms
- Biosimilars and Bioanalytical Methods
- Mental Health and Patient Involvement
- Renal and related cancers
- Pharmacological Receptor Mechanisms and Effects
- Respiratory viral infections research
- RNA and protein synthesis mechanisms
- Infection Control in Healthcare
- PARP inhibition in cancer therapy
- Endoplasmic Reticulum Stress and Disease
Icahn School of Medicine at Mount Sinai
2021-2024
Mount Sinai Health System
2023
University of California, San Francisco
2023
New York Proton Center
2022
University of San Francisco
2022
Mater Misericordiae University Hospital
2021
St. Vincent's University Hospital
2010
The emergence of SARS-CoV-2 variants concern suggests viral adaptation to enhance human-to-human transmission
Repurposing drugs as treatments for COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drawn much attention. Beginning with sigma receptor ligands and expanding to other from screening in field, we became concerned that phospholipidosis was a shared mechanism underlying antiviral activity of many repurposed drugs. For all 23 cationic amphiphilic tested, including hydroxychloroquine, azithromycin, amiodarone, four others already clinical trials,...
Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several variants in preclinical studies. Simultaneously, this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted 10 Spanish hospitals between May and November 2020, 46...
Abstract Identification of host determinants coronavirus infection informs mechanisms viral pathogenesis and can provide new drug targets. Here we demonstrate that mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) chromatin remodeling complexes, specifically canonical BRG1/BRM-associated factor (cBAF) promote severe acute respiratory syndrome 2 (SARS-CoV-2) represent host-directed therapeutic The catalytic activity SMARCA4 is required for mSWI/SNF-driven accessibility at the ACE2 locus,...
Abstract Variants of SARS-CoV-2 have become a major public health concern due to increased transmissibility, and escape from natural immunity, vaccine protection, monoclonal antibody therapeutics. The highly transmissible Omicron variant has up 32 mutations within the spike protein, many more than previous variants, heightening these concerns immune escape. There are now multiple antiviral therapeutics that received approval for emergency use by FDA target both RNA-dependent RNA polymerase...
The death toll and financial stress posed by the recent COVID-19 pandemic have highlighted pressing need to develop safe effective, broad-spectrum inhibitors treat viral infections. To accelerate antiviral drug discovery process, we developed GALILEOTM, a computational platform that interfaces with customizable bioinformatics pipeline geometric deep learning algorithm named ChemPrintTM for in silico screening. Combining these algorithms large chemical repositioning library, discovered...
ABSTRACT A series of SARS-CoV-2 variants concern (VOCs) have evolved in humans during the COVID-19 pandemic—Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic genomic analyses infection to understand molecular responses driving VOC evolution. We discovered VOC-specific differences viral RNA protein expression levels, including for N, Orf6, Orf9b, pinpointed several mutations responsible. An analysis host response comprehensive interrogation altered virus-host...
Abstract A strategy for pandemic preparedness is the development of antivirals against a wide set viral targets with complementary mechanisms action. SARS-CoV-2 nsp3-mac1 macrodomain ADP-ribosylhydrolase activity, which counteracts host immune response. Targeting virus’ immunomodulatory functionality offers differentiated to inhibit compared approved therapeutics, target replication directly. Here we report fragment-based lead generation campaign guided by computational approaches. We...
Influenza viruses cause approximately half a million deaths every year worldwide. Vaccines are available but partially effective, and the number of antiviral medications is limited. Thus, it crucial to develop therapeutic strategies counteract this major pathogen. enter host cell via their hemagglutinin (HA) proteins. The HA subtypes influenza A virus phylogenetically classified into groups 1 2. Here, we identified an inhibitor protein, tertiary aryl sulfonamide, that prevents entry...
More transmissible SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used global proteomic and genomic approaches to study host responses driving VOC evolution. We discovered VOCs evolved convergent strategies remodel response by modulating viral RNA protein levels, altering nucleocapsid phosphorylation, rewiring virus-host protein-protein interactions. Integrative systems analysis revealed that although Alpha, Beta, Gamma, Delta ultimately converged in...
Antiviral agents are needed for the treatment of SARS-CoV-2 infections and to control other coronavirus outbreaks that may occur in future. Here we report identification characterization RNA-binding compounds inhibit replication. The were detected by screening a small library antiviral previously shown bind HIV-1 or HCV RNA elements with live-virus cellular assay detecting inhibition These experiments allowed detection eight promising anti-SARS-CoV-2 activity sub-micromolar micromolar range...
Using Tecan D300e for serial dilution
Multiplicity of infection (MOI) is the ratio viral particles to cells. The ideal MOI for antiviral screenings will depend on several things - cell type, passage, virus amount cells, etc.
The following is a protocol for live virus antiviral screening against SARS-CoV-2 in vitro. Cells are prophylactically treated with candidates that have been serially diluted to investigate activity, via IC50 values generated analysis of immunofluorescent staining, SARS-CoV-2. You may opt include PgP inhibitor the assay by adding 2uM into infection media. Each accompanied matching cytotoxicity uninfected cells drug toxicity.
This protocol describes immunofluorescence staining of fixed SARS-CoV-2 infected cells using IC7C7 primary antibody (produced in house against NP) and Alexa Fluor 488-conjugated secondary antibody. The procedure results fluorescently labeled for quantification viral infection.
The following is a cytotoxicity protocol to be paired with live virus antiviral screening in vitro. Cells are prophylactically treated candidates that have been serially diluted investigate activity, via CC50 values generated analysis of MTT/MTS assays uninfected cells. You may opt include PgP inhibitor the assay by adding 2uM into infection media. For screenings for family you working on, will set up both an plate (infected) and (uninfected). measure compounds on
This describes generating Antiviral & Cytotoxicity Curves