U19AI171421

Development of Outpatient Antiviral Cocktails against SARS-CoV-2 and Other Potential Pandemic RNA Viruses

Abstract:
The overall platform and objective of the Stanford AVIDD Center, "SYNERX," is to develop outpatient antiviral cocktails against SARS-CoV-2 and other potential pandemic RNA viruses. Thus, the goal of each of our 7 projects is to develop towards the clinic a novel direct-acting antiviral (DAA) with a distinct mechanism of action, so that they can be used alone and in combination with other agents—providing additive, and ideally synergistic antiviral activity.

To maximize the achievement of this goal, we seek to create 3 scientific cores that will each provide critical expertise and resources:
1. The Structural Biology Core to offer critical insights into our projects' antiviral targets and mechanisms of action.
2. The Pandemic Assistance Core to ensure adequate access to facilities with the requisite biosafety and containment to safely develop our projects' antivirals against SARS-CoV-2 and other potential RNA pandemic viruses.
3. The Translation Accelerator Core, in which is embedded the Industry Consultants Consortium (ICC), to provide the requisite translational resources, industry rigor, and expertise to advance each project in a milestone and go/no-go driven fashion.

The range of planned activities spans the translational spectrum, from innovative target discovery and lead identification to lead optimization and IND-enabling activities. Our antiviral modalities include small molecules, nucleic acids, and protein therapeutics. Our lead programs have demonstrated proof-of-concept in vivo antiviral efficacy, with the potential to combat coronaviruses, as well as other RNA viruses of pandemic potential.

These efforts will include:
A) Targeting highly conserved RNA structures in viral RNA genomes with locked nucleic acid (LNA) antisense oligonucleotide (ASO) and small molecule therapeutics.
B) Improving formulations and delivery methods for nucleic acid therapeutics and targeting virus-derived circular RNAs.
C) Selectively targeting viral envelopes with antiviral peptides and peptoids.
D) Developing small molecule ligands of essential viral proteins that induce selective degradation of their protein targets.
E) Developing potent and selective inhibitors of essential proteases of SARS-CoV-2 and other RNA viruses.
F) Developing small molecule inhibitors of SARS-CoV-2 exonuclease to both promote lethal mutagenesis of the viral genome as well as enhance the antiviral efficacy of ribonucleoside analogs.
G) Developing small molecule inhibitors of SARS-CoV-2 NSP4's role in membrane-associated RNA replication.

We will establish an Administrative Core to effectively manage and optimally support the above, and provide critical regulatory expertise. Finally, we will leverage AVIDD funding with institutional support, matching philanthropy and industry partnerships, and strategic relationships to maximize preclinical development and ensure successful clinical and commercial development of SYNERX's most promising lead molecules.

Successful accomplishment of our aims will yield exciting synergistic outpatient antiviral cocktails for SARS-CoV-2 and other RNA viruses of pandemic potential.

The Leland Stanford Junior 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]

Stanford, California 94305 United States

Single Zip Code

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

COVID-19 $69,058,677 (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.