# In vivo virology core

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $3,760,731

## Abstract

CORE 7: IN VIVO VIROLOGY
SUMMARY
SARS-CoV-2 continues to cause severe morbidity and mortality in the current pandemic, and future RNA virus
epidemics or pandemics are inevitable. To improve patient mortality rates, the development of antiviral
therapeutics is critical. However, currently available SARS-CoV-2 antiviral treatments are limited in efficacy.
Furthermore, it is imperative that we have access to an arsenal of compounds against all RNA viruses of
pandemic potential ready to be deployed into clinical trials at the earliest stages of future pandemics to save
millions of lives and reduce long-term disabilities associated with disease.
The goal of the QCRG Pandemic Response Program is the identification and development of oral drug
candidates with suitable safety profiles for broad use in the outpatient setting. The In Vivo Virology Core plays
an essential role in the QCRG Drug Discovery Platform in the Hit-to-Lead and Lead Optimization stages, working
closely with Projects 1-6 and the In Vitro Virology and Medicinal Chemistry Cores. Our goal is to determine
the therapeutic efficacy of antiviral hits and leads against coronaviruses, flaviviruses, togaviruses, picornaviruses
and Bunyavirales in advanced animal models of viral infection.
We have assembled a team of investigators with decades of experience in advanced animal models for the
analysis of antiviral countermeasures against the target viral families. We will first analyze hit compounds in
animal models using single concentration prophylactic treatment of maximal tolerated dose. Compounds that
show antiviral activity against viruses in vitro (established by the In Vitro Virology core) and have a favorable
PK and toxicity profile in vivo (Medicinal Chemistry Core), will be tested for their ability to inhibit viral replication
and disease in mice challenged with coronaviruses, flaviviruses, enteroviruses, togaviruses, and bunyaviruses.
For compounds with antiviral activity in vivo in single-dose treatments, we will determine dose responses, time
of administration post-challenge for therapeutic activity, and spectrum of activity against multiple strains and
viruses (Aim 1). We expect to identify 8-12 or 8-10 Lead Compounds for coronaviruses and other pandemic-
potential RNA viruses, respectively. Next, in Aim 2, we will determine antiviral resistance patterns and fitness of
resistant mutantsIn addition, beneficial compound combinations identified in vitro (In Vitro Virology Core), will
be tested in drug combinations studies in the appropriate animal model, both with known virus inhibitors and with
each other. We anticipate being a key component for antiviral development and expect to iterate with Projects
and Cores to obtain 3-6 Optimized Leads that will be transferred to our industry partner Roche for clinical
development.

## Key facts

- **NIH application ID:** 10512625
- **Project number:** 1U19AI171110-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Adolfo Garcia-Sastre
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,760,731
- **Award type:** 1
- **Project period:** 2022-05-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512625

## Citation

> US National Institutes of Health, RePORTER application 10512625, In vivo virology core (1U19AI171110-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10512625. Licensed CC0.

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