Document text
Principal Investigator: John Damon Chodera
Organization: SLOAN-KETTERING INST CAN RESEARCH
Fiscal Year: 2024
Award: $528,000
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT - Overall
SARS-CoV-2 continues to cause severe morbidity and mortality in the ongoing pandemic. Future RNA virus
epidemics and pandemics are inevitable. New clinical-trial-ready antivirals are urgently needed RNA viruses of
pandemic potential. COVID-19 has further underscored the need for early, global access to clinic-ready
compounds. Beyond coronaviruses; flaviviruses and picornaviruses also cause frequent and ongoing epidemics
worldwide and have no effective therapeutics. Maintaining a portfolio of novel, clinic-ready therapeutics are
critical for our future pandemic preparedness.
The AI-driven Structure-enabled Antiviral Platform (ASAP) AViDD Center will develop novel chemical assets
that have antiviral activity against three target viral families. ASAP will leverage state-of-the-art structure-enabled
technologies capable of leveraging recent advances in AI/ML and computational chemistry in identifying,
enabling, and prosecuting discovery campaigns against novel viral targets. ASAP is built on principles of open
science and rapid dissemination (enabled by a dedicated Data Infrastructure Core).
ASAP builds on the successful COVID Moonshot, an open science collaboration that recently secured $11 million
from the Wellcome Trust via the WHO Access to COVID Tools Accelerator (ACT-A) to fund preclinical
development of a novel oral noncovalent SARS-CoV-2 antiviral acting against the main protease (MPro).
Beginning with a high-throughput X-ray fragment screen, the discovery team spent just 18 months and $1M to
reach the preclinical phase. ASAP will mirror this rapid, cost-efficient approach: automated structural biology at
Diamond Light Source (Frank von Delft); AI/ML synthesis models from PostEra (Alpha Lee); nanoscale
chemistry and covalent fragment libraries from Nir London; massively distributed free energy calculations on
Folding@home (John Chodera); an industrial medicinal chemistry team led by MedChemica (Ed Griffen);
and antiviral assays and virology expertise at Mount Sinai (Kris White; Adolfo García-Sastre). ASAP
augments this seasoned antiviral discovery team with new approaches to resistance-robust targeting (Karla
Kirkegaard and Matt Bogyo, Stanford) and deep mutational scanning (Jesse Bloom, Fred Hutch). ASAP is
supported by the Drugs for Neglected Diseases Initiative (DNDi) (PI Ben Perry), and Letters of Support from
Takeda, Pfizer, Novartis, and Grupo Insud.
ASAP Impact: ASAP will become the nexus of a robust global antiviral discovery community. Our open science
approach focuses on ensuring global, equitable access to therapeutics to combat future pandemics. We aim
to produce a robust antiviral pipeline consisting of 3 new Phase I ready candidates, 6 lead optimization
campaigns, 9 fragment-to-lead campaigns, and 10 structure-enabled resistance-robust viral targets. Our
associated data packages will accelerate follow-on development and investment.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Acceleration><Administrative Efficiency><Anti-viral Agents><Assay><Bioassay><Biological Assay><Biology><COVID-19><COVID-19 anti-viral><COVID-19 antiviral><COVID-19 virus><COVID19 virus><CV-19><Chemicals><Chemistry><CoV-2><CoV2><Collaborations><Communication><Communities><Complement><Complement Proteins><Complex><Coronaviridae><Coronavirus><Coronavirus Infectious Disease 2019><Data><Decision Making><Dedications><Development><Diamond><Disease><Disorder><Drugs><Elements><Ensure><Epidemic><Equity><Esteroproteases><Family><Family Picornaviridae><Flavivirus><Free Energy><Funding><Future><Generations><Goals><Group B Arbovirus><Home><Industrial Medicine><Investigational New Drug Application><Investigators><Investments><Lead><Leadership><Letters><Libraries><Light><Link><London><MSKCC><Medication><Medicinal Chemistry><Medicine><Memorial Sloan-Kettering Cancer Center><Mentors><Mission><Modeling><Morbidity><Morbidity - disease rate><NIAID><National Institute of Allergy and Infectious Disease><Occupational Medicine><Occupational or Industrial Medicine><Oral><Orthoflavivirus><Output><Pb element><Peptidases><Peptide Hydrolases><Pharmaceutic Chemistry><Pharmaceutical Chemistry><Pharmaceutical Preparations><Phase><Photoradiation><Picornaviridae><Picornaviruses><Productivity><Protease Gene><Proteases><Proteinases><Proteolytic Enzymes><R-Series Research Projects><R01 Mechanism><R01 Program><RNA Viruses><Reagent><Refractory><Research><Research Contracts><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resistance><Resources><Roentgen Rays><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 anti-viral><SARS-CoV-2 antiviral><SARS-CoV2><SARS-CoV2 anti-viral><SARS-CoV2 antiviral><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Seasons><Secure><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 coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Source><Structure><Technology><Therapeutic><Translations><Trust><Viral><Viral Activity><Viral Function><Viral Physiology><Work><Wuhan coronavirus><X-Radiation><X-Ray Radiation><X-ray><Xray><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><clinic ready><clinical ready><clinical translation><clinical trial readiness><clinically translatable><combat><complementation><computational chemistry><corona virus><coronavirus disease 2019><coronavirus disease 2019 anti-viral><coronavirus disease 2019 antiviral><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cost efficient><dashboard><data infrastructure><design><designing><developmental><drug discovery><drug/agent><epidemic virus><experience><future pandemic><hCoV19><heavy metal Pb><heavy metal lead><homes><industrial partnership><industry partner><industry partnership><innovate><innovation><innovative><lead optimization><meeting><meetings><mortality><mutation scanning><mutation screening><nCoV2><nano meter scale><nano meter sized><nanometer scale><nanometer sized><nanoscale><neglect><new approaches><new technology><next pandemic><novel><novel approaches><novel strategies><novel strategy><novel technologies><open data><open science><open-source data><operation><operations><pandemic><pandemic concern><pandemic disease><pandemic disease preparedness><pandemic planning><pandemic potential><pandemic preparedness><pandemic readiness><pandemic risk><pandemic threat><pre-clinical><pre-clinical development><pre-clinical study><preclinical><preclinical development><preclinical study><programs><recruit><resilience><resilient><resistant><severe acute respiratory syndrome coronavirus 2 anti-viral><severe acute respiratory syndrome coronavirus 2 antiviral><structural biology><therapeutically effective><tool><translation><virology>