R01AI160953

Fusion inhibitors that block host-to-host transmission of SARS-CoV-2 - coronaviruses (CoVs) can cause life-threatening diseases. The recently emerging coronavirus-related illness was named Coronavirus Disease 2019 (abbreviated "COVID-19") by the World Health Organization. COVID-19 is caused by SARS-CoV-2. Like its predecessors SARS-CoV and MERS-CoV, SARS-CoV-2 (S-CoV-2) is a betacoronavirus that is thought to have originated in bats. Originally, its spread was animal-to-human, but human-to-human transmission is now widespread.

No vaccines and treatments for COVID-19 are available, and these are urgently needed to address the outbreak as well as inevitable ongoing infection. Antivirals that target viral entry into the host cell have been proven effective against a wide range of viruses. In this proposal, we will apply the results of our fundamental research to the development of novel peptide inhibitors of SARS-CoV-2 entry.

We have designed lipid-conjugated fusion-inhibitory peptides that efficiently inhibit coronavirus infection in in vitro, ex vivo, and in vivo. We propose to synthesize and evaluate novel lipidated peptides that have enhanced efficacy. These inhibitors will be evaluated for antiviral activity against live SARS-CoV-2 virus. Promising candidates will be tested in transmission experiments in a ferret model. This application will determine whether our approach to entry inhibition of SARS-CoV-2 prevents infection in vivo.

The objectives of this proposal are:

1. To optimize antiviral potency of HRC-lipopeptide fusion inhibitors.
2. To pre-clinically evaluate HRC-lipopeptide fusion inhibitors' biodistribution, toxicity, and protection against SARS-CoV-2 infection or transmission in vivo.

The Trustees Of Columbia University In The City Of New York

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]

New York, New York 100323723 United States

Single Zip Code

Emergency Awards: Rapid Investigation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) (R01 Clinical Trial Not Allowed) (PAR-20-178)

COVID-19 $1,430,732 (40%) percent of this Project Grant was funded by COVID-19 emergency acts including the 2020 Coronavirus Preparedness and Response Supplemental Appropriations Act and the American Rescue Plan Act of 2021.
Amendment Since initial award the total obligations have increased 377% from $750,151 to $3,574,588.