# SARS-CoV-2 and Autophagy

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $424,875

## Abstract

PROJECT SUMMARY/ABSTRACT
Coronaviruses are major causes of disease worldwide, from the common cold to outbreaks of strains causing
severe and sometimes lethal respiratory distress, including SARS, MERS, and the current outbreak of COVID-
19 caused by SARS-CoV-2. It has been observed over the last two decades that multiple coronaviruses
interact with components of the autophagy pathway to rearrange cellular membranes and generate sites for
RNA replication. In this application, we propose to test the interactions of SARS-CoV-2 with the autophagy
pathway. We will rapidly assess whether SARS-CoV-2 has similar interactions with the autophagy pathway as
other coronaviruses, then extend the field by identifying how these interactions interfere with viral replication,
providing novel therapeutic targets. We will carry this strategy out through three Aims: In the first, we will
identify requirements from the early autophagy pathway for SARS-CoV-2 replication. Data from coronavirus
studies suggest that the autophagy protein LC3 is recruited to generate double membraned vesicles for virus
genomic RNA replication. Other data suggest LC3 is utilized through the ER-associated degradation (ERAD)
machinery to generate replication vesicles. We will determine which, if either, of these two pathways is used by
SARS-CoV-2. In the second aim, we will determine the role of vesicle acidification in SARS-CoV-2 replication.
There is strong evidence that acidification of vesicles plays a role in multiple steps of CoV replication, and we
will identify the role of vesicle acidification in SARS-CoV-2 replication. In the third aim, we will identify the
specific roles of SARS-CoV-2 non-structural proteins in induction of the autophagic machinery. We have
identified previous studies of expression of non-structural proteins in coronavirus and will use this to guide our
study of SARS-CoV-2 proteins. These Aims complement existing studies of autophagy in RNA viral life cycles
by the Jackson Lab while leveraging the existing expertise of the Frieman Lab in studying cell biology of
coronavirus infections. By completing these Aims, we will understand whether SARS-CoV-2 interacts with the
autophagy pathway in a similar or unique fashion compared to other coronaviruses, and extend the
coronavirus field by identifying specific host-virus interactions that may be targeted for COVID-19 therapies.

## Key facts

- **NIH application ID:** 10174059
- **Project number:** 1R21AI158134-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** William T Jackson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $424,875
- **Award type:** 1
- **Project period:** 2020-07-14 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174059

## Citation

> US National Institutes of Health, RePORTER application 10174059, SARS-CoV-2 and Autophagy (1R21AI158134-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10174059. Licensed CC0.

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