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Principal Investigator: John Damon Chodera
Organization: SLOAN-KETTERING INST CAN RESEARCH
Fiscal Year: 2022
Award: $6,599,276
Funding agency: National Institute of Allergy and Infectious Diseases
SARS-CoV-2 continues to cause severe morbidity and mortality in the current pandemic and future RNA virus
pandemics are inevitable. Clinical-trial-ready antivirals are lacking for all RNA viruses of pandemic potential. It
is imperative that the world have access to an arsenal of compounds ready to be deployed into clinical trials at
the earliest stages of future pandemics. Beyond coronaviruses; flaviviruses and picornaviruses have caused
frequent and ongoing epidemics around the world and there are currently no effective therapeutics available.
These viral families have proven to be major threats to the human population and novel IND-ready
therapeutics will be critical for our future pandemic preparedness.
The ASAP AViDD Center is dedicated to the development of novel chemical matter with antiviral activity
against these three viral families. The focus on targets refractory to antiviral resistance by Project 1: Antiviral
Targeting to Suppress Drug Resistance and the Target Enabling Packages (TEPs) developed by Project 2:
Target Enablement are highly innovative approaches that will allow the ASAP consortium to efficiently develop
novel antivirals with the potential for sustained clinical success. The Antiviral Efficacy and Resistance Core
plays an essential role in the ASAP Center, firstly as the primary site for in vitro screening and primary cell
models, with support from Johan Neyts {KU Leuven) as a secondary in vitro screening laboratory. We will also
perform comprehensive in vitro and in vivo antiviral resistance analysis and drug combination studies. Finally,
we will work closely with Projects 1-6, the NIAID, and industry partners to select leads to move into in vivo
analysis and determine the therapeutic efficacy of antiviral leads against these three viral families in advanced
animal models of viral infection. We have assembled a team of investigators in our core with decades of
experience in cell culture and advanced animal models for the analysis of antiviral countermeasures against
the target viral families.
A major goal of the ASAP Center is the identification and development of 3 oral antiviral drug candidates with
suitable safety profiles for broad use in the outpatient setting. We have placed an emphasis on the
identification of novel antiviral targets using advanced resistance-refractory target selection, Al-based
fragment-based screening, structural enablement of these targets, and a comprehensive efficacy and
resistance analysis. The Antiviral Efficacy and Resistance Core will be integrated into the ASAP platform by
working with the consortium, the NIAID, and industry partners to select 45-50 of our top antiviral leads to test in
our advanced animal models of viral infection. We will then advance up to 15 advanced leads into
comprehensive in vivo efficacy analysis, and finally select 3 leads to move into in vivo resistance mutation
analysis and drug combination studies using well-established methods in our laboratories.
Project Summary/
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Animal Model><Animal Models and Related Studies><Anti-viral Drug Resistance><Anti-viral Drug Resistant><Antiviral Agents><Antiviral Drug Resistance><Antiviral Drug Resistant><Antiviral Drugs><Antiviral resistance><Antiviral resistant><Antivirals><Assay><Bioassay><Bioavailability><Biologic Assays><Biologic Availability><Biologic Models><Biological Assay><Biological Availability><Biological Models><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID19 vaccine><COVID19 virus><Cell Body><Cell Culture Techniques><Cell model><Cells><Cellular model><Chemicals><Clinical><Clinical Trials><CoV-2><CoV2><Contracting Opportunities><Contracts><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Development><Drug Combinations><Drug resistance><EC 2.7.7.48><Epidemic><Family><Family Picornaviridae><Family member><Flavivirus><Flavivirus Infections><Future><Generations><Genetic Alteration><Genetic Change><Genetic Diversity><Genetic Variation><Genetic defect><Goals><Group B Arbovirus><HCoV><High Throughput Assay><Human><Immunization Programs><In Vitro><Influenza Virus><Institutes><Investigators><Laboratories><Lead><Lytotoxicity><Measures><Medical Research><Methods><Model System><Modern Man><Morbidity><Morbidity - disease rate><Mutation><Mutation Analysis><NIAID><National Institute of Allergy and Infectious Disease><Oral><Out-patients><Outpatients><Pattern><Pb element><Physiologic Availability><Picornaviridae><Picornaviridae Infections><Picornavirus Infections><Picornaviruses><Play><Population><Prevention><Probability><Process><RNA Replicase><RNA Viruses><RNA-Dependent RNA Polymerase><RNA-Directed RNA Polymerase><Refractory><Replication Unit><Replicon><Research Personnel><Researchers><Resistance><Resistance profile><Resistant profile><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Scheme><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 CoV 2 vaccine><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 vaccine><Severe acute respiratory syndrome related corona virus 2><Site><Structure><Testing><Therapeutic><Time><Transmission><Treatment Efficacy><Vaccination Programs><Viral><Viral Diseases><Viral Drug Resistance><Viral Genome><Viral Pathogenesis><Virus><Virus Diseases><Work><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><anti-viral agents><anti-viral compound><anti-viral development><anti-viral drug development><anti-viral drugs><anti-viral efficacy><anti-viral medication><anti-viral resistance><anti-viral resistant><anti-viral therapeutic><anti-viral therapeutic development><anti-viral therapy development><anti-virals><antiviral compound><antiviral development><antiviral drug development><antiviral efficacy><antiviral medication><antiviral therapeutic><antiviral therapeutic development><antiviral therapy development><base><cell culture><cell cultures><corona virus><corona virus disease 2019 vaccine><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19 vaccine><coronavirus disease-19 virus><cytotoxicity><developing anti-viral agent><developing anti-viral drug><developing anti-viral therapeutic><developing anti-viral therapy><developing antiviral agent><developing antiviral drug><developing antiviral therapeutic><developing antiviral therapy><developmental><drug candidate><drug discovery><drug resistant><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><emerging pathogen><evaluate efficacy><examine efficacy><experience><fitness><genome mutation><hCoV19><heavy metal Pb><heavy metal lead><high throughput screening><human CoV><human corona virus><human coronavirus><human pathogen><improved><in vivo><industrial partnership><industry partner><industry partnership><influenzavirus><innovate><innovation><innovative><intervention efficacy><medical college><medical schools><model of animal><model organism><mortality><mutant><nCoV2><new pathogen><novel><novel pathogen><pandemic><pandemic disease><pandemic preparedness><programs><rational design><resistance mutation><resistance to Drug><resistance to anti-viral><resistance to antiviral><resistant><resistant mutation><resistant to Drug><resistant to anti-viral><resistant to antiviral><school of medicine><screening><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><social role><success><therapeutic efficacy><therapeutically effective><therapy efficacy><transmission process><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine for novel coronavirus><variants of concern><viral fitness><viral infection><viral resistance><virus genome><virus infection><virus pathogenesis><virus resistance><virus-induced disease><weapons>