A5068049292- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Tuberculosis Research and Epidemiology
- Long-Term Effects of COVID-19
- Mycobacterium research and diagnosis
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Intensive Care Unit Cognitive Disorders
- Muscle activation and electromyography studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cancer therapeutics and mechanisms
- Diabetic Foot Ulcer Assessment and Management
- COVID-19 and Mental Health
- Osteoarthritis Treatment and Mechanisms
- Biochemical and Molecular Research
- Viral gastroenteritis research and epidemiology
- Infectious Diseases and Tuberculosis
- Synthesis of β-Lactam Compounds
- Vaccine Coverage and Hesitancy
- Pneumocystis jirovecii pneumonia detection and treatment
- Neuropeptides and Animal Physiology
- Immunodeficiency and Autoimmune Disorders
- Pain Mechanisms and Treatments
- Transgenic Plants and Applications
- Virus-based gene therapy research
Regeneron (United States)
2021-2024
Cornell University
2014-2019
Weill Cornell Medicine
2016-2019
Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option COVID-19. Because rapidly emerging virus mutants becoming the next major concern in fight global pandemic, it is imperative that these treatments provide coverage circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated sequence diversity spike protein monitored emergence SARS-COV-2 isolates found COVID-19 patients treated with...
Mycobacterium tuberculosis (Mtb) encounters stresses during the pathogenesis and treatment of (TB) that can suppress replication bacteria render them phenotypically tolerant to most available drugs. Where studied, majority Mtb in sputum untreated subjects with active TB have been found be nonreplicating by criterion they do not grow as colony-forming units (cfus) when plated on agar. However, these cells are viable because diluted liquid media. A method for generating such "differentially...
Significance Better understanding of the mechanisms used by bacteria to counter antibacterial agents is essential cope with rising prevalence antimicrobial resistance. Here, we identified mechanism resistance Mycobacterium tuberculosis an antimycobacterial cyano-substituted fused pyrido-benzimidazole. Clones bearing mutations in a transcription factor, Rv2887, markedly up-regulated expression rv0560c , putative methyltransferase. Rv0560c N -methylated pyrido-benzimidazole vitro and...
It is urgent to introduce new drugs for tuberculosis shorten the prolonged course of treatment and control drug-resistant Mycobacterium (Mtb). One strategy toward this goal develop antibiotics that eradicate both replicating (R) nonreplicating (NR) Mtb. Naturally occurring (+)-calanolide A was active against R-Mtb. The present report details design, synthesis, antimycobacterial activities, structure-activity relationships synthetic calanolides. We identified potent dual-active...
Open-label platform trials and a prospective meta-analysis suggest efficacy of anti-interleukin (IL)-6R therapies in hospitalized patients with coronavirus disease 2019 (COVID-19) receiving corticosteroids. This study evaluated the safety sarilumab, an anti-IL-6R monoclonal antibody, treatment COVID-19.
Abstract Background The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD). Methods In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta Omicron, hospitalized COVID-19 were randomized (1:1:1) 2.4 g or 8.0 CAS IMD placebo, characterized at baseline for viral load serostatus. Results total, 1336 on low-flow no supplemental...
Identification of compounds that target metabolically diverse subpopulations Mycobacterium tuberculosis (Mtb) may contribute to shortening the course treatment for tuberculosis. This study screened 270,000 from GlaxoSmithKline's collection against Mtb in a nonreplicating (NR) state imposed vitro by combination four host-relevant stresses. Evaluation 166 confirmed hits led detailed characterization 19 potency, specificity, cytotoxicity, and stability. Compounds representing five scaffolds...
The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU discrimination bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, time. Testing compounds against M. under conditions prevent the replication often involves a second phase test which altered to permit bacteria survived first phase. False-positive determinations may arise carryover stage assay act stage. We mitigate these...
ABSTRACT BACKGROUND Sarilumab (anti-interleukin-6 receptor-α monoclonal antibody) may attenuate the inflammatory response in Covid-19. METHODS We performed an adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial of intravenous sarilumab 200 mg or 400 adults hospitalized with The 3 primary analysis population (cohort 1) was patients critical Covid-19 receiving mechanical ventilation (MV) randomized to placebo. end point for proportion ≥1-point improvement clinical status...
The success of Mycobacterium tuberculosis (Mtb) as a pathogen depends on the redundant and complex mechanisms it has evolved for resisting nitrosative oxidative stresses inflicted by host immunity. Improving our understanding these defense pathways can reveal vulnerable points in Mtb pathogenesis. In this study, we combined genetic, structural, computational, biochemical, biophysical approaches to identify novel enzyme class represented Rv2466c. We show that Rv2466c is mycothiol-dependent...
Summary Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option COVID-19. As rapidly emerging virus mutants becoming the next major concern in fight global pandemic, it is imperative that these treatments provide coverage circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated sequence diversity spike protein monitored emergence minor SARS-COV-2 isolates found COVID-19 patients or identified from...
Firstly, this study demonstrated that natural product-inspired coumarin-based nitrofuranyl calanolides (NFCs) can form the Rv2466c-mycothiol (MSH)-NFC (RvMN) ternary complex via NFC binding to W21, N51, and Y61 of Rv2466c be specifically reduced by Rv2466c, which is accompanied generation a high level fluorescence. Additionally, results unveiled acetylated cysteine–glucosamine (AcCys-GlcN) motif MSH sufficient interact with adopt active conformation essential for fully reducing NFCs. Further...
The historical view of β-lactams as ineffective antimycobacterials has given way to growing interest in the activity this class against Mycobacterium tuberculosis (Mtb) presence a β-lactamase inhibitor. However, most antimycobacterial kill Mtb only or best when bacilli are replicating. Here, screen 1904 led identification cephalosporins substituted with pyrithione moiety at C3′ that active under both replicating and nonreplicating conditions, neither requiring Studies showed required situ...
Abstract Background Hospitalized patients with COVID-19 experience high mortality rates, ranging from 10% to 30%. Combined casirivimab and imdevimab (CAS+IMD) is authorized for use in outpatients post-exposure prophylaxis. The UK-based platform RECOVERY study reported improved survival hospitalized seronegative treated CAS+IMD; however, most of the world, anti-spike monoclonal antibody therapy currently not approved patients. Methods In this phase I/II/III double-blind placebo-controlled...
We conducted a post hoc analysis in seropositive patients who were negative or borderline for functional neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline from phase 1, 2, and 3 trial of casirivimab imdevimab (CAS+IMD) treatment hospitalized disease 2019 (COVID-19) on low-flow no supplemental oxygen prior to the emergence Omicron-lineage variants. Patients randomized single dose 2.4 g CAS+IMD, 8.0 placebo. anti-SARS-CoV-2 analyzed...
The artemin-GFRα3 signaling pathway has been implicated in various painful conditions including migraine, cold allodynia, hyperalgesia, inflammatory bone pain, and mouse knees contain GFRα3-immunoreactive nerve endings. We developed high affinity (REGN1967) human (REGN5069) GFRα3-blocking monoclonal antibodies and, following vivo evaluations models of chronic joint pain (osteoarthritic-like inflammatory), conducted a first-in-human phase 1 pharmacokinetics (PK) safety trial REGN5069...
Gait is impaired in musculoskeletal conditions, such as knee arthropathy. analysis used clinical practice to inform diagnosis and monitor disease progression or intervention response. However, gait relies on subjective visual observation of walking objective has not been possible within settings due the expensive equipment, large-scale facilities, highly trained staff required. Relatively low-cost wearable digital insoles may offer a solution these challenges. In this work, we demonstrate...
Abstract Background The field of long COVID research is rapidly evolving, however, tools to assess and monitor symptoms recovery the disease are limited. objective present study was develop a new patient-reported outcomes instrument, Symptoms Evolution Long COVID‑19 (SE-LC19), establish its content validity. Methods 40-item SE-LC19 instrument developed based on patient-relevant empirical evidence from scientific literature clinical guidelines that reported specific COVID. A 2-part...
There is an urgent need to discover and progress anti-infectives that shorten the duration of tuberculosis (TB) treatment. Mycobacterium tuberculosis, etiological agent TB, refractory rapid lasting chemotherapy due presence bacilli exhibiting phenotypic drug resistance. The charcoal agar resazurin assay (CARA) was developed as a tool characterize active molecules discovered by high-throughput screening campaigns against replicating non-replicating M. tuberculosis. Inclusion activated in...
Abstract As part of a program to explore the chemistry β‐lactams and their derivatives, we prepared focused set benzazetidine, indoline, indole heterocycles, as well flexible unconstrained variations four‐membered heterocyclic compounds. These analogues mimic three‐dimensional shape cephalosporins but are not prone covalent binding via ring opening. Although these were inactive against ESKAPE pathogens Mtb , they represent unique underexplored chemotypes for future biological screening.
There is an urgent need to discover and progress anti-infectives that shorten the duration of tuberculosis (TB) treatment. Mycobacterium tuberculosis, etiological agent TB, refractory rapid lasting chemotherapy due presence bacilli exhibiting phenotypic drug resistance. The charcoal agar resazurin assay (CARA) was developed as a tool characterize active molecules discovered by high-throughput screening campaigns against replicating non-replicating M. tuberculosis. Inclusion activated in...
Abstract Background Individuals who are immunocompromised (IC) at high risk for severe coronavirus disease 2019 (COVID-19). Methods Post hoc analyses of a double-blind trial conducted prior to Omicron (June 2020–April 2021), in hospitalized patients with COVID-19 assessed viral load, clinical outcomes, and safety casirivimab plus imdevimab (CAS + IMD) versus placebo IC overall study patients. Results Ninety-nine 1940 (5.1%) were IC. more frequently seronegative acute respiratory syndrome 2...