Document text
Principal Investigator: John Schneekloth
Organization: DIVISION OF BASIC SCIENCES - NCI
Fiscal Year: 2022
Award: $324,711
Funding agency: National Cancer Institute
Traditional drug screening strategies are based on targeting coronavirus-related proteins (e.g., RdRp, Mpro, and 3CLpro) and receptors (e.g. ACE2). In addition to virus-coded proteins, RNA structures within the SARS-CoV-2 genome also regulate essential functions and are potentially attractive and complementary targets for small molecules. RNA-targeting compounds would represent a highly novel approach for developing anti-SARS-CoV-2 therapeutics. The SARS-CoV-2 genome is a 29.9 kB, positive-sense, single-stranded RNA. Several regions within in the genome likely encode functions critical to virus replication. Here, we focus on two specific RNA elements, the frameshifting element (FSE) pseudoknot and the Stem-loop II-like motif (s2m) hairpin, both of which have been shown to form unique and stable three-dimensional structures. However, our efforts need not be limited to these structures: as continued information becomes available we aim to apply SMM screening to new structured regions of the SARS-CoV-2 genome as well. This proposal aims to discover drug-like small molecules that target functional elements within the SARS-CoV-2 genome as mechanistically novel antiviral compounds via a collaboration exploiting unique expertise of the participating labs.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><3-D structure><3-dimensional structure><3D structure><ACE2><Antiviral Agents><Antiviral Drugs><Antivirals><COVID-19 genome><COVID-19 outbreak><COVID-19 therapeutics><COVID-19 virus><COVID-19 virus genome><COVID19 genome><COVID19 outbreak><COVID19 therapeutics><COVID19 virus><COVID19 virus genome><Clinical Trials><CoV-2><CoV2><Code><Coding System><Collaborations><Coronaviridae><Coronavirus><Drug Design><Drug Screening><Drugs><Economics><Elements><Functional RNA><GS-5734><Genome><Medication><Non-Coding><Non-Coding RNA><Non-Polyadenylated RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><Pharmaceutic Preparations><Pharmaceutical Preparations><Proteins><RNA><RNA Gene Products><Receptor Protein><Ribonucleic Acid><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 genome><SARS-CoV-2 outbreak><SARS-CoV-2 therapeutics><SARS-CoV2><SARS-CoV2 genome><SARS-CoV2 outbreak><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 therapeutics><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 outbreak><Severe acute respiratory syndrome coronavirus 2 therapeutics><Severe acute respiratory syndrome related corona virus 2><Structure><Therapeutic><Untranslated RNA><Veklury><Virus><Virus Replication><Wuhan coronavirus><angiotensin converting enzyme 2><angiotensin converting enzyme II><anti-viral agents><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><antiviral compound><antiviral medication><antiviral therapeutic><base><beta CoV><beta coronavirus><betaCoV><betacoronavirus><corona virus><coronavirus disease 2019 genome><coronavirus disease 2019 outbreak><coronavirus disease 2019 therapeutics><coronavirus disease 2019 virus><coronavirus disease 2019 virus genome><coronavirus disease-19 outbreak><coronavirus disease-19 virus><drug/agent><hCoV19><mortality><nCoV2><new approaches><noncoding><novel><novel approaches><novel strategies><novel strategy><receptor><remdesivir><screening><severe acute respiratory syndrome coronavirus 2 genome><small molecule><stem><therapeutics against COVID-19><therapeutics against COVID19><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><three dimensional structure><viral multiplication><viral replication><virus multiplication><β CoV><β coronavirus><βCoV>