Development of COVID-19 cell entry inhibitors
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Principal Investigator: Nadya Tarasova Organization: DIVISION OF BASIC SCIENCES - NCI Fiscal Year: 2024 Award: $32,788 Funding agency: National Cancer Institute We have identified several inhibitors of STAT3 N-terminal domain that has been shown to mediate inflammatory effects of the virus, and contribute to "long COVID". The lead compound turned out to be stable in human plasma. However, its half life in the mouse plasma was less than 5 minutes. The later complicates further preclinical development of this lead. We have now generated several derivatives that lack the unstable ester bond. In vitro testing of these derivative and further characterization is in progress. Terms: <Binding><Blood Plasma><COVID-19><COVID-19 therapeutics><COVID-19 therapy><COVID-19 treatment><CV-19><Cell Body><Cells><Chemical Structure><Chemicals><Coronaviridae Infections><Coronavirus Infections><Coronavirus Infectious Disease 2019><Data><Data Bases><Databases><Development><Docking><Drug Screening><Drug Therapy><E coli><E. coli><Eligibility><Eligibility Determination><Escherichia coli><Esters><Evaluation><Generations><Goals><Half-Life><High Throughput Assay><Human><Inflammatory><Lead><Libraries><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Mediating><Methods><Mice><Mice Mammals><Modern Man><Molecular Interaction><Murine><Mus><N-terminal><NH2-terminal><Pb element><Pharmacotherapy><Plasma><Plasma Serum><Property><Proteins><Protocol Screening><Recombinants><Reticuloendothelial System, Serum, Plasma><SARS-CoV-2 therapeutics><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-coronavirus-2 therapeutics><STAT3><STAT3 gene><Severe acute respiratory syndrome coronavirus 2 therapeutics><Structure><Viral><Viral Gene Products><Viral Gene Proteins><Viral Proteins><Virus><biophysical approaches><biophysical methodology><biophysical methods><biophysical techniques><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><coronavirus disease 2019><coronavirus disease 2019 therapeutics><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease-19><coronavirus infectious disease-19><data base><developmental><drug treatment><heavy metal Pb><heavy metal lead><high throughput screening><improved><in silico><in vitro testing><inhibitor><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><novel><persistent COVID-19><physical state><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><pre-clinical development><pre-clinical study><preclinical development><preclinical study><prolonged COVID-19 symptoms><protein structure><protein structures><proteins structure><screening><screenings><severe acute respiratory syndrome coronavirus 2 therapy><severe acute respiratory syndrome coronavirus 2 treatment><small molecule><therapeutics against COVID-19><therapeutics against SARS-CoV-2><therapeutics against SARS-coronavirus-2><therapeutics against Severe acute respiratory syndrome coronavirus 2><therapeutics against coronavirus disease 2019><therapeutics for novel coronavirus><treat COVID-19><treat SARS-CoV-2><treat coronavirus disease 2019><treat severe acute respiratory syndrome coronavirus 2><virtual library><virus protein>