Proceedings of the National Academy of Sciences

Shared host genetic landscape of respiratory viral infection

L Leah B. Soriaga (Vir Biotechnology Inc.) D Dale R. Balce (Vir Biotechnology Inc.) I Istvan Bartha (Vir Biotechnology Inc.) A Arnold Park (Vir Biotechnology Inc.) E Emily Wong (Vir Biotechnology Inc.) M Michael McAllaster (Vir Biotechnology Inc.) E Elizabeth A. Mueller (Vir Biotechnology Inc.) O Ona Barauskas (Vir Biotechnology Inc.) E Esteban Carabajal (Vir Biotechnology Inc.) B Beatriz Kowalski (Vir Biotechnology Inc.) S Sooyoung Lee (Vir Biotechnology Inc.) G Gary Lo (Vir Biotechnology Inc.) T Tara F. Mahoney (Vir Biotechnology Inc.) M Matteo Metruccio (Vir Biotechnology Inc.) A Anna Sahakyan (Vir Biotechnology Inc.) L Logeshwaran Somasundaram (Vir Biotechnology Inc.) T Tod Steinfeld (Vir Biotechnology Inc.) L Lisha Wang (Michigan Center for Translational Pathology, University of Michigan) L Laura Wedel (Vir Biotechnology Inc.) S Samantha S. Yim (Vir Biotechnology Inc.) L Li Yin (Vir Biotechnology Inc.) J Jiayi Zhou (Vir Biotechnology Inc.) Z Zach Newby (Vir Biotechnology Inc.) W Winston Tse (Vir Biotechnology Inc.) J Johannes Grosse (Vir Biotechnology Inc.) H Herbert W. Virgin (Vir Biotechnology Inc.) S Seungmin Hwang (Vir Biotechnology Inc.) A Amalio Telenti (Vir Biotechnology Inc.)

Abstract

Respiratory viruses represent a major global health burden. Although these viruses have different life cycles, they may depend on common host genetic factors, which could be targeted by broad-spectrum host-directed therapies. We used genome-wide CRISPR screens and advanced data analytics to map a network of host genes that support infection by nine human respiratory viruses [influenza A virus, parainfluenza virus, human rhinovirus, respiratory syncytial virus, human coronavirus (HCoV)-229E, HCoV-NL63, HCoV-OC43, Middle East respiratory syndrome–related coronavirus, and severe acute respiratory syndrome–related coronavirus 2]. We explored shared pathways using knowledge graphs to inform on pharmacological targets. We selected and validated STT3A/B proteins of the N-oligosaccharyltransferase complex as host targets of broad-spectrum antiviral small molecules. Our work highlights the commonalities of viral host genetic dependencies and the feasibility of using this information to develop broad-spectrum antiviral agents.

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Article Details

Volume / Issue Vol. 122, Issue 20
Published May 20, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Journal Info

Proceedings of the National Academy of Sciences

National Academy of Sciences
ISSN: 0027-8424 Life Sciences

Authors (28)

L

Leah B. Soriaga

Vir Biotechnology Inc.

D

Dale R. Balce

Vir Biotechnology Inc.

I

Istvan Bartha

Vir Biotechnology Inc.

A

Arnold Park

Vir Biotechnology Inc.

E

Emily Wong

Vir Biotechnology Inc.

M

Michael McAllaster

Vir Biotechnology Inc.

E

Elizabeth A. Mueller

Vir Biotechnology Inc.

O

Ona Barauskas

Vir Biotechnology Inc.

E

Esteban Carabajal

Vir Biotechnology Inc.

B

Beatriz Kowalski

Vir Biotechnology Inc.

S

Sooyoung Lee

Vir Biotechnology Inc.

G

Gary Lo

Vir Biotechnology Inc.

T

Tara F. Mahoney

Vir Biotechnology Inc.

M

Matteo Metruccio

Vir Biotechnology Inc.

A

Anna Sahakyan

Vir Biotechnology Inc.

L

Logeshwaran Somasundaram

Vir Biotechnology Inc.

T

Tod Steinfeld

Vir Biotechnology Inc.

L

Lisha Wang

Michigan Center for Translational Pathology, University of Michigan

L

Laura Wedel

Vir Biotechnology Inc.

S

Samantha S. Yim

Vir Biotechnology Inc.

L

Li Yin

Vir Biotechnology Inc.

J

Jiayi Zhou

Vir Biotechnology Inc.

Z

Zach Newby

Vir Biotechnology Inc.

W

Winston Tse

Vir Biotechnology Inc.

J

Johannes Grosse

Vir Biotechnology Inc.

H

Herbert W. Virgin

Vir Biotechnology Inc.

S

Seungmin Hwang

Vir Biotechnology Inc.

A

Amalio Telenti

Vir Biotechnology Inc.

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