U19AI171110

QCRG Pandemic Response Program - QCRG Pandemic Response Program Overall Summary. The QCRG (Quantitative Biosciences Institute Coronavirus Research Group) Pandemic Response Program is an interdisciplinary program that aims to identify new direct-acting antivirals for SARS-CoV-2 and 19 other viruses. The proposal brings together a team of 45 investigators from 14 different institutions with a history of collaboration; 31 of these have co-published together on 25 papers on SARS-CoV-2,1–25 efforts that have laid a strong foundation for the QCRG Pandemic Response Program.

Initially, we will focus on eight target classes from eight viral families (Coronaviridae, Picornaviridae, Togaviridae, Flaviviridae, Hantaviridae, Arenaviridae, Nairoviridae, and Paramyxoviridae), including seven coronaviruses, with a focus on SARS-CoV-2, where the viral RNA and 12 proteins will be targeted. In addition to the SARS-CoV-2 RNA (Project 1), we will target the NSP3 PLP and NSP5 Mpro proteases (Project 2); the NSP3 macrodomain (Project 5); the RdRp polymerase, NSP7, NSP8, and NSP12 (Project 2); the structural proteins E (Project 3), N (Project 6), and M (Projects 3 and 6); the methyltransferases NSP10/16 and NSP14 (Project 4); and the accessory protein involved in regulating the immune response, ORF9B (Project 6). Although we will focus on SARS-CoV-2, related proteins from 19 other viruses will also be targeted.

Using the QCRG drug discovery platform, we will perform screens on these targets, involving fragment campaigns, virtual library docking, and high-throughput screens, to discover inhibitors, which will be optimized using cycles of design, structure determination, and testing. In vitro and in vivo pharmacokinetics as well as activity in cellular and mouse models of infection will be carried out, followed by studies involving oral bioavailability, clearance, permeability, solubility, metabolic liabilities, toxicity, and efficacy. The final goal of each project is an optimized lead ready for clinical development at Roche (see letter of support from Dr. John Young, Head of Infectious Diseases) and other industry partners.

Throughout, we will exploit an integrated suite of experimental and computational technologies provided by eight cores. The Biochemistry Core will provide purified material for the Screening Core, while the structures of targets and compounds will be determined through the cryo-EM, cryo-ET, and crystallography capabilities of the Structural Biology Core. State-of-the-art mass spectrometry in the Proteomics Core will provide mechanistic insight into the effects of compounds on their targets. The Medicinal Chemistry Core will optimize potent on-target compounds and work closely with the In Vitro Virology Core and In Vivo Virology Core to measure and optimize antiviral activity. The Integrative Modeling Core will provide computational support to structure determination and inhibitor discovery throughout the QCRG drug discovery platform. The Administrative Core will provide leadership, help to foster a collaborative environment, and manage the mentored projects and the developmental research projects, which will bring in new investigators.

San Francisco Regents Of The University Of California

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

California United States

State-Wide

Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern (U19 Clinical Trial Not Allowed) (RFA-AI-21-050)

COVID-19 $67,452,049 (100%) percent of this Cooperative Agreement was funded by COVID-19 emergency acts including the American Rescue Plan Act of 2021.
Amendment Since initial award the End Date has been extended from 04/30/25 to 04/30/26.