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tRNA-derived RNA Fragments and their Role in Nasal SARS-CoV-2 Infection

Award Number: R21AI166543
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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tRNA-derived RNA Fragments and their Role in Nasal SARS-CoV-2 Infection - The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging pathogenic virus, has resulted in not only the coronavirus disease 2019 (COVID-19) pandemic, but also economic recession. To strategically develop antiviral therapies against SARS-CoV-2, a focused effort in identifying mechanisms on how the host responds to SARS-CoV-2 is urgently needed. Non-coding RNAs (ncRNAs) contribute to 98% of human transcriptional products and are promising therapeutic targets against viral infections. One effective example for utilizing ncRNAs as promising therapeutic targets is that miR122 inhibitor RG-101 suppresses the hepatitis C virus (HCV) with a single dose. Therefore, studying the ncRNA responses for emerging viruses may provide a shortcut to developing effective therapeutic interventions. We recently discovered that the most impacted small ncRNAs (sncRNAs) by SARS-CoV-2 in nasal swab samples belong to tRNA-derived RNA Fragments (tRFs), a recently discovered ncRNA family. We also found that SARS-CoV-2-induced tRFs are unlikely to be degradation byproducts, but tightly regulated molecules, and nasal airway epithelial cells (AECs) can recapitulate tRF induction by SARS-CoV-2. Compared with tRFs induced by hepatitis viruses and respiratory syncytial virus (RSV), SARS-CoV-2-induced tRFs share several features with them. Given the emerging roles of tRFs in other viral infections, including our early observation on their proviral role in RSV infection and our preliminary data validating a SARS-CoV-2-induced tRF being important in regulating viral RNA synthesis, we hypothesize that SARS-CoV-2-induced tRFs are also functionally important to SARS-CoV-2 infection. We will address the hypothesis by 1) characterizing tRF signatures, and 2) investigating whether tRFs affect SARS-CoV-2 replication and associated host responses. UTMB is the home of the BSL4 Galveston National Laboratory (GNL), a leading resource for our national response to emerging infectious diseases. The GNL obtained the first sample of SARS- CoV-19 at the end of January of 2020, and is currently conducting research on all fronts; basic, animal, clinical trials, and epidemiological. We have an ongoing collaboration with co-investigator Dr. Tian Wang, who is an expert in studying host responses to BSL3 RNA viruses. Her laboratory has established a protocol to purify SARS-CoV-2 for the infection. We recently have been working together on AEC models to study the interaction between host and SARS-CoV-2. The results of this project will not only provide the potential to determine the molecular mechanisms associated with the replication and pathogenesis of SARS-CoV-2, but also are highly instructive for the development of potential disease biomarkers and therapeutic strategies for SARS-CoV-2. In conclusion, the overall goal of our team is to provide ncRNAs-related information for designing novel antiviral drugs.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2027 ( Subtotal = -$2,465 )
2027	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	2	10/20/2026	NON-COMPETING CONTINUATION	-$2,465
														Subtotal = -$2,465

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	2	5/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $440,000 )
2023	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	001	2	6/30/2023	SUPPLEMENT FOR EXPANSION	$240,000
2023	2023	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	2	6/16/2023	NON-COMPETING CONTINUATION	$200,000
														Subtotal = $440,000

Issue Date FY: 2022 ( Subtotal = $240,000 )
2022	2022	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	1	6/29/2022	NEW	$240,000
														Subtotal = $240,000

Grand Total All Awards = $677,535

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tRNA-derived RNA Fragments and their Role in Nasal SARS-CoV-2 Infection

Award Number: R21AI166543

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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