# QCRG Pandemic Response Program

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $67,452,049

## Abstract

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 t...

## Key facts

- **NIH application ID:** 10512617
- **Project number:** 1U19AI171110-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nevan J Krogan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,452,049
- **Award type:** 1
- **Project period:** 2022-05-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512617

## Citation

> US National Institutes of Health, RePORTER application 10512617, QCRG Pandemic Response Program (1U19AI171110-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10512617. Licensed CC0.

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