U19AI171403

Antiviral Countermeasures Development Center (AC/DC) - The Antiviral Countermeasures Development Center (AC/DC) will target pathogens in five families of RNA viruses with significant pandemic potential. The overarching goal is to identify and develop orally bioavailable, direct-acting antiviral drugs (DAAs). Specific viral targets include zoonotic and human viruses in the coronavirus, paramyxovirus, flavivirus, picornavirus, and togavirus families.

The AC/DC MPIs, Drs. Painter and Plempar, who will lead this effort, have demonstrated the power of their combined expertise in identifying novel antiviral chemotypes and advancing them from the hit stage to clinical candidate. Their successful joint work on molnupiravir, considered for emergency approval as the first oral therapeutic for the treatment of COVID-19, exemplifies their achievements. The MPIs have assembled a team of recognized experts in the biology of the viral pathogens being targeted. Their efforts are organized into five synergistic projects supported by cutting-edge technical expertise in five AC/DC scientific cores, covering key areas of preclinical drug discovery and development. Several core leaders have significant experience in the development of antivirals in the pharma and biotechnology sectors.

The AC/DC will achieve its overarching goal through two major objectives. Pilot studies identified two chemically distinct broad-spectrum ribonucleoside analogs and two non-nucleoside viral polymerase inhibitors with confirmed oral efficacy against one or several of the five viral families targeted. This includes a novel chemotype that is orally efficacious against SARS-CoV-2 in relevant animal models. Objective 1 will advance this set of four novel DAA leads through final synthetic optimization and de-risking in animal models and primary human organoids as immediate deliverables to mitigate the urgent threat to public health.

Simultaneously, Objective 2 will identify additional viable hit chemotypes to expand the AC/DC's antiviral portfolio. This will be achieved by leveraging center expertise in reverse genetics of all viral target families, existing groundbreaking reporter virus technologies, and high-throughput screening under standard and high biocontainment conditions. Hits will be counterscreened against all center target families, molecular viral targets, and mechanism of action characterized. A potency, pharmacokinetics, and pharmacophore-driven synthetic development program will be launched to identify optimized leads.

All data generated by the projects and cores will be evaluated center-wide utilizing quantitative performance milestones of a defined AC/DC lead advancement cascade. This cascade governs the progression of a chemotype from hit to clinical development candidate.

Emory University

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]

Georgia 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 $51,914,880 (100%) percent of this Cooperative Agreement was funded by COVID-19 emergency acts including the American Rescue Plan Act of 2021.