A5054884687- SARS-CoV-2 and COVID-19 Research
- Cardiomyopathy and Myosin Studies
- RNA and protein synthesis mechanisms
- COVID-19 Clinical Research Studies
- Bacteriophages and microbial interactions
- Cardiovascular Effects of Exercise
- Trypanosoma species research and implications
- Muscle Physiology and Disorders
- Cytomegalovirus and herpesvirus research
- Parasitic Infections and Diagnostics
- Influenza Virus Research Studies
- Toxoplasma gondii Research Studies
- Viral Infections and Immunology Research
- Pneumonia and Respiratory Infections
- Amyotrophic Lateral Sclerosis Research
- Viral gastroenteritis research and epidemiology
- Cardiovascular Function and Risk Factors
- Neurogenetic and Muscular Disorders Research
- Animal Virus Infections Studies
- Ubiquitin and proteasome pathways
- SARS-CoV-2 detection and testing
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Bacterial Genetics and Biotechnology
- Ferroptosis and cancer prognosis
University of California, Berkeley
2020-2025
Molecular Sciences Institute
2025
Cytokinetics (United States)
2016-2024
Center for Discovery
2022-2023
Berkeley College
2020
Howard Hughes Medical Institute
2006-2007
Harvard University
2006-2007
Max Planck Institute of Biochemistry
2002-2003
Max Planck Society
2002
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes Disease 2019 (COVID-19), a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. of the viral nascent virion is mediated nucleocapsid (N) protein, but underlying mechanism remains unclear. Here, we show N protein forms biomolecular condensates with genomic both vitro and mammalian While spherical assemblies homopolymeric...
Hypercontractility of the cardiac sarcomere may be essential for underlying pathological hypertrophy and fibrosis in genetic hypertrophic cardiomyopathies. Aficamten (CK-274) is a novel myosin inhibitor that was discovered from optimization indoline compound 1. The important advancement discovery an Indane analogue (12) with less restrictive structure-activity relationship allowed rapid improvement drug-like properties. designed to provide predicted human half-life (t1/2) appropriate once...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild illness to distress syndrome. A systematic understanding host factors influencing viral infection is critical elucidate SARS-CoV-2-host interactions and the progression Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout activation screens human lung epithelial cells with endogenous expression SARS-CoV-2 entry ACE2 TMPRSS2. We uncovered...
Abstract The COVID-19 pandemic is exacting an increasing toll worldwide, with new SARS-CoV-2 variants emerging that exhibit higher infectivity rates and may partially evade vaccine antibody immunity. Rapid deployment of non-invasive therapeutic avenues capable preventing infection by all could complement current vaccination efforts help turn the tide on pandemic. Here, we describe a novel strategy targeting RNA using locked nucleic acid antisense oligonucleotides (LNA ASOs). We identify LNA...
Hypertrophic cardiomyopathy (HCM) is an inherited disease of the sarcomere resulting in excessive cardiac contractility. The first-in-class myosin inhibitor, mavacamten, improves symptoms obstructive HCM. Here we present aficamten, a selective small-molecule inhibitor that diminishes ATPase activity by strongly slowing phosphate release, stabilizing weak actin-binding state. Binding to allosteric site on catalytic domain distinct from aficamten prevents conformational changes necessary enter...
Abstract SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy moderate, improved treatment strategies are urgently needed. To accomplish goal, we devised strategy to identify compounds that act synergistically remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), has emerged as a major global health threat. The COVID-19 pandemic resulted in over 168 million cases and 3.4 deaths to date, while number continues rise. With limited therapeutic options, identification safe effective therapeutics is urgently needed. repurposing known clinical compounds holds potential for rapid drugs against SARS-CoV-2. Here, we utilized library FDA-approved...
This study presented a novel screening of acrylamides discovering them as inhibitors against Nsp15 from SARS-CoV-2 and utilizing the data to develop an AI model screen more virtually.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes COVID-19, a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. of the viral nascent virion is mediated nucleocapsid (N) protein, but underlying mechanism remains unclear. Here, we show N protein forms biomolecular condensates with genomic both vitro and mammalian Phase separation driven, part, hydrophobic electrostatic...
Abstract Malaria results in more than 500,000 deaths per year and the causative Plasmodium parasites continue to develop resistance all known agents, including different antimalarial combinations. The class XIV myosin motor PfMyoA is part of a core macromolecular complex called glideosome, essential for parasite mobility therefore an attractive drug target. Here, we characterize interaction small molecule (KNX-002) with PfMyoA. KNX-002 inhibits ATPase activity vitro blocks asexual blood...
We have addressed how ribosome-nascent chain complexes (RNCs), associated with the signal recognition particle (SRP), can be targeted to Sec61 translocation channels of endoplasmic reticulum (ER) membrane when all binding sites are occupied by nontranslating ribosomes. These competing ribosomes known bound high affinity tetramers complex. found that RNC-SRP does not require or cause dissociation prebound ribosomes, a process is extremely slow. SRP and its receptor target RNCs free population...
The identification and optimization of the first activators fast skeletal muscle are reported. Compound 1 was identified from high-throughput screening (HTS) subsequently found to improve function via interaction with troponin complex. Optimization for potency, metabolic stability, physical properties led discovery tirasemtiv (25), which has been extensively characterized in clinical trials treatment amyotrophic lateral sclerosis.
The SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with currently 29 million confirmed cases and close to a deaths. At this time, there are no FDA-approved vaccines or therapeutics for COVID-19, but Emergency Use Authorization been granted remdesivir, broad-spectrum antiviral nucleoside analog. However, remdesivir is only moderately efficacious against SARS-CoV-2 in the clinic, improved treatment strategies urgently needed. To accomplish goal, we devised strategy...
The discovery of reldesemtiv, a second-generation fast skeletal muscle troponin activator (FSTA) that increases force production at submaximal stimulation frequencies, is reported. Property-based optimization high throughput screening hit 1 led to compounds with improved free exposure and in vivo activation potency compared the first-generation FSTA, tirasemtiv. Reldesemtiv demonstrated increased generation phase clinical trial currently being evaluated trials for treatment amyotrophic...
Toxoplasma gondii is a widespread apicomplexan parasite that can cause severe disease in its human hosts. The ability of T . and other parasites to invade into, egress from, move between cells the hosts they infect critical virulence progression. An unusual highly conserved myosin motor (TgMyoA) plays central role motility. goal this work was determine whether parasite’s motility lytic cycle be disrupted through pharmacological inhibition TgMyoA, as an approach altering progression vivo. To...
The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication allowing the virus to evade host immune response. Inhibitors of PLpro have great therapeutic potential, however, developing them has been challenging due PLpro's restricted substrate binding pocket. In this report, we screened 115 000-compound library inhibitors identified new pharmacophore, based on mercapto-pyrimidine fragment that reversible covalent inhibitor...