A5054630199- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Computational Drug Discovery Methods
- Viral Infections and Immunology Research
- Microbial Natural Products and Biosynthesis
- Bacillus and Francisella bacterial research
- Synthetic Organic Chemistry Methods
- Phytochemistry and Biological Activities
- Insect Resistance and Genetics
- vaccines and immunoinformatics approaches
- Respiratory viral infections research
- Chemical synthesis and alkaloids
- Malaria Research and Control
- Bacteriophages and microbial interactions
- Essential Oils and Antimicrobial Activity
- Fungal Biology and Applications
- Virus-based gene therapy research
- Insect and Pesticide Research
- Plant Pathogens and Fungal Diseases
- Bioactive Compounds and Antitumor Agents
- Radiopharmaceutical Chemistry and Applications
- Biological Activity of Diterpenoids and Biflavonoids
Aaron Diamond AIDS Research Center
2015-2024
Columbia University
2020-2024
Columbia College
2021-2024
Royal College of Physicians
2021-2024
Aster Medcity
2023
Columbia University Irving Medical Center
2023
North Bristol NHS Trust
2022
North Middlesex Hospital
2020
Middlesex University
2020
Cohen Children's Medical Center
2019
Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States South Africa, respectively 1,2 . These new carrying further mutations their spike proteins raise concerns that they may evade neutralizing antibodies, thereby compromising efficacy of COVID-19 vaccines therapeutic monoclonals. We now report findings from a systematic antigenic analysis these surging subvariants. is only modestly (1.8-fold) more resistant sera vaccinated...
The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this rest on development effective interventions. Single combination monoclonal antibody (mAb) therapeutics have received emergency use authorization 1–3 , with more in pipeline 4–7 . Furthermore, multiple vaccine constructs shown promise 8 including two ~95% protective efficacy against 9,10 However, these interventions were directed toward initial SARS-CoV-2 that emerged...
Abstract Since the start of COVID-19 pandemic, SARS-CoV-2 has caused millions deaths worldwide. Although a number vaccines have been deployed, continual evolution receptor-binding domain (RBD) virus challenged their efficacy. In particular, emerging variants B.1.1.7, B.1.351 and P.1 (first detected in UK, South Africa Brazil, respectively) compromised efficacy sera from patients who recovered immunotherapies that received emergency use authorization 1–3 . One potential alternative to avert...
Abstract The Covid-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this rest on development effective interventions. Two monoclonal antibody (mAb) therapeutics have received emergency use authorization, more are in pipeline. Furthermore, multiple vaccine constructs shown promise, including two with ~95% protective efficacy against Covid-19. However, these interventions were directed toward initial SARS-CoV-2 that emerged 2019....
Recent months have seen surges of SARS-CoV-2 infection across the globe with considerable viral evolution 1-3 . Extensive mutations in spike protein may threaten efficacy vaccines and therapeutic monoclonal antibodies 4 Two signature concern are E484K, which plays a crucial role loss neutralizing activity antibodies, N501Y, driver rapid worldwide transmission B.1.1.7 lineage. Here, we report emergence variant lineage B.1.526 that contains E484K its alarming rise to dominance New York City...
SUMMARY The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been described recently. We now report that another emergent variant from Brazil, P.1, is not only refractory multiple neutralizing monoclonal antibodies, but also more resistant by convalescent plasma (3.4 fold) vaccinee sera (3.8-4.8 fold). cryo-electron microscopy structure a soluble prefusion-stabilized spike reveals the P.1 trimer adopt exclusively conformation in which one...
Abstract SARS-CoV-2 infections have surged across the globe in recent months, concomitant with considerable viral evolution 1–3 . Extensive mutations spike protein may threaten efficacy of vaccines and therapeutic monoclonal antibodies 4 Two signature concern are E484K, which has a crucial role loss neutralizing activity antibodies, N501Y, driver rapid worldwide transmission B.1.1.7 lineage. Here we report emergence variant lineage B.1.526 (also known as Iota 5 ), contains its rise to...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (T H 1)–biased CD4 response elicited neutralizing antibodies wild type concern, as well SARS-CoV-1....
The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.
Abstract The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation replication cycle. Based on conservation of substrate binding pockets across coronaviruses using screening, we identified four structurally distinct lead compounds that inhibit protease. After evaluation their specificity, cellular antiviral potency, metabolic stability, water solubility, prioritized GC376 scaffold as being...
Abstract Background The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear. Methods We characterized 2,875 from the National Basketball Association occupational health cohort identified between June 2020 January 2022 using serial RT-qPCR testing. Logistic regression semi-mechanistic RNA models were used to quantify effect variant, symptom status, age, infection history, vaccination antibody titer founder strain duration potential...
COVID-19 patients commonly present with signs of central nervous system and/or peripheral dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection DA triggers an inflammatory cellular senescence response. High-throughput screening in hPSC-derived identified several FDA-approved drugs can rescue the...
We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 as inhibitors SARS-CoV-2 3CL protease. Structures each these in complex with protease revealed strategies for further development, well general principles designing inhibitors. These may therefore serve leads basis building effective
Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or N-terminal (NTD). Over a dozen neutralizing NTD-directed antibodies have been studied structurally, and all single antigenic supersite in NTD (site 1). Here, we report cryo-EM structure of potent antibody 5-7, which recognizes site distinct from other antibodies, inserting binding loop into an exposed hydrophobic pocket between two sheets β sandwich. Interestingly, this was previously identified as...