A5091699013- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Influenza Virus Research Studies
- Biosensors and Analytical Detection
- Respiratory viral infections research
- Long-Term Effects of COVID-19
- Mosquito-borne diseases and control
- Advanced biosensing and bioanalysis techniques
- PARP inhibition in cancer therapy
- Artificial Intelligence in Healthcare
- HIV Research and Treatment
- Telemedicine and Telehealth Implementation
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Gut microbiota and health
- interferon and immune responses
- Microfluidic and Bio-sensing Technologies
- Synthesis and biological activity
- Advanced Biosensing Techniques and Applications
- Viral Infections and Immunology Research
- Virology and Viral Diseases
- Carbohydrate Chemistry and Synthesis
- Viral Infections and Vectors
- RNA and protein synthesis mechanisms
University of California, San Diego
2020-2025
UC San Diego Health System
2022
Abstract We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain binds ACE2. In vitro, binding of ACE2 heparin ectodomains occurs independently ternary complex can be generated using as template. Contrary purified components, on cells codependently. Unfractionated heparin, non-anticoagulant...
Remdesivir (RDV; GS-5734) is currently the only FDA-approved antiviral drug for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The approved use in adults or children 12 years older who are hospitalized COVID-19 on basis an acceleration clinical recovery inpatients with this disease. Unfortunately, must be administered intravenously, restricting its to those requiring hospitalization relatively advanced RDV also unstable plasma and has a complex...
Changes in lung ACE2 expression and apoptotic priming throughout life span may affect COVID severity.
Abstract We isolated a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2 variant from person with disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Antiviral sensitivity and neutralizing antibody testing were performed both parental SARS-CoV-2 multiple variants of concern. found that neither nirmatrelvir resistance nor absence immunity was likely cause the recrudescence.
We isolated a SARS-CoV-2 BA.2 variant from person with COVID-19 recrudescence after nirmatrelvir/ritonavir treatment. Antiviral sensitivity and neutralizing antibody testing was performed compared parental multiple variants of concern. found that neither NM resistance nor absence immunity were likely causes the recrudescence.
We report a silver nanoparticle (AgNP) sensor array to detect SARS-CoV-2 viral particles utilizing five peptide receptors produce colorimetric response. show that the interaction of virus with peptides interferes shift in plasmonic absorbance and hinders formation snowflake-like fractal assemblies between AgNPs bridging peptides. The limit detection water was 500,000 copies/mL. demonstrate capabilities distinguish (Beta, Delta, Omicron variants) from influenza at 99% confidence level through...
Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used engineered angiotensin-converting enzyme to from plasma and other complex biofluids. leverages a staggered herringbone pattern, nanoparticle surface coating, processing conditions achieve detection as few 3...
The emergence of Zika virus (ZIKV) as a global health threat has highlighted the unmet need for ZIKV-specific vaccines and antiviral treatments. ZIKV infects dendritic cells (DC), which have pivotal functions in activating innate adaptive responses; however, mechanisms by DC function is subverted to establish infection are unclear. Here we develop genomics profiling method that enables discrete analysis ZIKV-infected versus neighboring, uninfected primary human DCs increase sensitivity...
Abstract Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening glycosyltransferases mainly performed by in vitro enzyme assays with difficulties moving candidates to cells animals. Here, we circumvent this employing a cell-based screening assay using glycoengineered expressing tailored reporter glycoproteins. We focused on GalNAc-type O-glycosylation selected the GalNAc-T11 isoenzyme that selectively...
We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain binds ACE2. In vitro, binding of ACE2 heparin ectodomains occurs independently ternary complex can be generated using as template. Contrary purified components, on cells codependently. Unfractionated heparin, non-anticoagulant treatment...
ABSTRACT The gastrointestinal (GI) tract is a site of replication severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa known to modify. To explore gut HS-modifying bacterial abundances how their presence may impact infection, we developed task-based analysis proteoglycan degradation on large-scale shotgun...
ABSTRACT Remdesivir (RDV, GS-5734) is currently the only FDA-approved antiviral drug for treatment of SARS CoV-2 infection. The approved use in adults or children 12-years older who are hospitalized COVID-19 on basis an acceleration clinical recovery inpatients with this disease. Unfortunately, must be administered intravenously, restricting its to those requiring hospitalization relatively advanced RDV also unstable plasma and has a complex activation pathway which may contribute highly...
We identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone 1 , a compound in clinical trials for anti-fibrotic and anti-inflammatory applications 2 as potent of SARS-CoV-2 infection replication. The interaction spike protein with cell surface heparan sulfate (HS) promotes viral entry 3 . find that reduces HS biosynthesis, thereby reducing binding, pseudotyped virus, authentic infection. Halofuginone also potently suppresses replication post-entry is 1,000-fold more than Remdesivir 4...
The factors contributing to the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.4 and BA.5 subvariants in populations that experienced recent surges BA.2 BA.2.12.1 infections are not understood. Neutralizing antibodies (NAbs) likely protect against disease if present sufficient quantity. We found after or infection, NAb responses were largely cross-neutralizing but much less effective BA.5. In addition, individuals who infected treated early with...
Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis evaluation alkyl glyceryl ether phosphodiesters GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability stability in plasma. Oral SARS-CoV-2-infected BALB/c mice with 1-
The continuing mutability of the SARS-CoV-2 virus can result in failures diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance inactivated variant panels provided to Radical Acceleration Diagnostics programs (RADx)-radical program awardees. A heuristic genetic analysis based on variant-defining mutations demonstrated lowest variance Nucleocapsid protein (Np)-C-terminal domain (CTD) across all...
Plasmonic nanoparticle-based biosensors often report a colorimetric signal through the aggregation or clustering of nanoparticles (NPs), but these mechanisms typically struggle to function in complex biofluids. Here, we matrix-insensitive sensor array approach detect bacteria, fungi, and viruses whose is based on dissociation peptide-aggregated NPs by thiolated polyethylene glycol (HS-PEG) polymers. We show that HS-PEGs differing sizes have varying capabilities dissociate citrate-capped gold...
Broad spectrum oral antivirals are urgently needed for the early treatment of many RNA viruses clinical concern. We previously described synthesis 1-O-octadecyl-2-O-benzyl-glycero-3-phospho-RVn (V2043), an orally bioavailable lipid prodrug remdesivir nucleoside (RVn, GS-441524) with broad antiviral activity against pandemic potential. Here we compared relative V2043 new RVn prodrugs containing sn-1 alkyl ether or sn-2 glycerol modifications. found that 3-F-4-MeO-Bn, 3-CN-Bn, and 4-CN-Bn...
ABSTRACT Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1- O -octadecyl-2- -benzyl- sn -glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug GS-441524 (remdesivir nucleoside, RVn), demonstrated its in vivo efficacy SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) 4-cyano-benzyl (V2067), that...
The continuing mutability of the SARS-CoV-2 virus can result in failures diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance inactivated SARS-COV-2 variant panels provided to Radical Acceleration Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated lowest variance Nucleocapsid protein (Np)- C-terminal domain (CTD) across...
SARS-CoV-2 antibody levels have been proposed as a correlate of protection (CoP) from infection. Yet, large-scale prospective studies cost-effective scalable measures predictors infection under real-world conditions are limited. We examined whether measured using high-throughput variant-specific anti-spike immunoglobulin G (IgG) and ACE2-neutralization assays with cell-based neutralizing (NAb) measurements, they can serve reasonable CoP