# In vitro virology core

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $7,437,530

## Abstract

CORE 6: IN VITRO VIROLOGY
SUMMARY
QCRG Pandemic Response Program In Vitro Virology Core leverages in-depth virology expertise from 10
groups to support Projects 1–6 in discovering and developing antivirals against coronaviruses and other RNA
viruses with pandemic potential. The goal is to identify lead compounds from hits using live-virus assays and
channel them, in an iterative process, through lead optimization to obtain Optimized Leads for each project. The
In Vitro Virology Core is led by Melanie Ott (Gladstone, UCSF) and supported by co-Is Adolfo Garcia-Sastre,
Ana Sesma (Icahn School of Medicine at Mt Sinai), Greg Towers, Clare Jolly (University College London),
Luis Martinez-Sobrido (UT San Antonio), Marco Vignuzzi, Carla Saleh (Institut Pasteur), and Lorena Zuliani-
Alvarez (UCSF). We will provide live virus, reverse genetics and subgenomic virological assays in cell lines and
advanced primary cell models for 20 RNA viruses, including various coronaviruses, picornaviruses, togaviruses,
flaviviruses, paramyxoviruses and bunyavirales. We will also provide tight organizational oversight with precisely
defined and safe work- and data flows, central interpretation of results, and guidance on pan-antiviral potential
of lead compounds. In Vitro Virology Core members will meet monthly and interface tightly with all projects and
cores. Aim 1 will test inhibitors against coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2, hCoV-OC43,
NL63, 229E and HKU1) in a tiered approach, initially using nanoluciferase SARS-CoV-2 reporter virus assays
and later parallel, multi-site IC50, IC90 and CC50 determinations with various SARS-CoV-2 isolates. Compounds
will be selected for further evaluation of their: (a) pan-coronavirus inhibition, (b) efficacy in lung organoids and
primary lung epithelial cells grown at the air-liquid interface, (c) mechanism of action (with the Proteomics Core),
and (d) combination studies including polymerase inhibitors remdesivir and molnupiravir. Resulting leads will be
serially passaged in cell lines to identify drug-resistance mutations that will be cloned into SARS-CoV-2
molecular clones and studied for lead optimization. We will also provide reagents and pre-formed virus-like
particles to Projects 3 and 6 for hit identification. Aim 2 will test inhibitors against other RNA viruses with
pandemic potential, including enteroviruses EV-A71 and EV-D68, chikungunya virus, coxsackie viruses,
poliovirus, rhinovirus, zika and dengue viruses and paramyxovirus, in live virus assays using viral isolates and
engineered molecular clones. In a tiered approach similar to Aim 1, Target Characterization, Hit-to-Lead, and
Lead Optimization steps will be performed in appropriate cell lines, as well as in lung and gut organoids and
tonsil histocultures. Combination and resistance studies will be performed as described above and will include
the pan-serotype dengue inhibitor JNJ-A07. If appropriate, we will test lead compounds from Aim 1 for antiviral
act...

## Key facts

- **NIH application ID:** 10512624
- **Project number:** 1U19AI171110-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Melanie Maria Ott
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $7,437,530
- **Award type:** 1
- **Project period:** 2022-05-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512624

## Citation

> US National Institutes of Health, RePORTER application 10512624, In vitro virology core (1U19AI171110-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10512624. Licensed CC0.

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