Document text
Principal Investigator: Michael R. Farzan
Organization: SCRIPPS RESEARCH INSTITUTE, THE
Fiscal Year: 2022
Award: $1,876,244
Funding agency: National Institute of Allergy and Infectious Diseases
SUMMARY
Coronaviruses, including SARS-CoV-2, pose obvious and imminent dangers to public health. This
CAMPP proposal develops compounds that target multiple coronaviruses proteins and replication
processes. These proteins include well established drug targets such as protease (Project 1) and
replicase (Project 2), and as well as higher risk targets (Project 4). Project 3 – Targeting Druggable
Coronavirus Proteins focuses on four less established viral processes that nonetheless have been
successfully targeted in at least one proof-of-principle example. These include the coronaviral helicase
nsp13 (Aim 1, led by Sumit Chandra at Scripps Research), the nucleocapsid (N) protein, which packages
the RNA genome and associates with the budding virion (Aim 2, led by Suganya Selvarajah at Prosetta),
the E protein, which encodes an ion channel whose activity likely contributes to virion assembly (Aim 3,
led by John Guatelli from UCSD), and the spike (S) protein with mediates fusion of the viral and cellular
membranes (Aim 4, lead by Michael Farzan at Scripps Florida). These four targets afford four parallel
“shots on goal”. In each case, the lead laboratory has identified novel proof-of-principle chemical matter
inhibiting the activity of each protein. These compounds are developed through a common pipeline, and
in parallel each aim pursues a custom high-throughput screen designed to address the challenges unique
to each target. In the later years of the proposal developmental resources are allocated to the most
promising compounds. The overall structure of this proposal is thus designed to maximize the chance of
developing an effective inhibitor or coronavirus replication.
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