tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2025 May 20;122(20):e2414202122.
doi: 10.1073/pnas.2414202122. Epub 2025 May 15. Shared host genetic landscape of respiratory viral infection
Leah B Soriaga[SUP] #[/SUP][SUP] 1 [/SUP], Dale R Balce[SUP] #[/SUP][SUP] 1 [/SUP], Istvan Bartha[SUP] #[/SUP][SUP] 1 [/SUP], Arnold Park[SUP] #[/SUP][SUP] 1 [/SUP], Emily Wong[SUP] 1 [/SUP], Michael McAllaster[SUP] 1 [/SUP], Elizabeth A Mueller[SUP] 1 [/SUP], Ona Barauskas[SUP] 1 [/SUP], Esteban Carabajal[SUP] 1 [/SUP], Beatriz Kowalski[SUP] 1 [/SUP], Sooyoung Lee[SUP] 1 [/SUP], Gary Lo[SUP] 1 [/SUP], Tara F Mahoney[SUP] 1 [/SUP], Matteo Metruccio[SUP] 1 [/SUP], Anna Sahakyan[SUP] 1 [/SUP], Logeshwaran Somasundaram[SUP] 1 [/SUP], Tod Steinfeld[SUP] 1 [/SUP], Lisha Wang[SUP] 1 [/SUP], Laura Wedel[SUP] 1 [/SUP], Samantha S Yim[SUP] 1 [/SUP], Li Yin[SUP] 1 [/SUP], Jiayi Zhou[SUP] 1 [/SUP], Zach Newby[SUP] 1 [/SUP], Winston Tse[SUP] 1 [/SUP], Johannes Grosse[SUP] 1 [/SUP], Herbert W Virgin[SUP] 1 [/SUP], Seungmin Hwang[SUP] 1 [/SUP], Amalio Telenti[SUP] 1 [/SUP]
Affiliations
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.
Keywords: CRISPR; functional genomics; genome-wide; host-directed therapy; respiratory virus.
. 2025 May 20;122(20):e2414202122.
doi: 10.1073/pnas.2414202122. Epub 2025 May 15. Shared host genetic landscape of respiratory viral infection
Leah B Soriaga[SUP] #[/SUP][SUP] 1 [/SUP], Dale R Balce[SUP] #[/SUP][SUP] 1 [/SUP], Istvan Bartha[SUP] #[/SUP][SUP] 1 [/SUP], Arnold Park[SUP] #[/SUP][SUP] 1 [/SUP], Emily Wong[SUP] 1 [/SUP], Michael McAllaster[SUP] 1 [/SUP], Elizabeth A Mueller[SUP] 1 [/SUP], Ona Barauskas[SUP] 1 [/SUP], Esteban Carabajal[SUP] 1 [/SUP], Beatriz Kowalski[SUP] 1 [/SUP], Sooyoung Lee[SUP] 1 [/SUP], Gary Lo[SUP] 1 [/SUP], Tara F Mahoney[SUP] 1 [/SUP], Matteo Metruccio[SUP] 1 [/SUP], Anna Sahakyan[SUP] 1 [/SUP], Logeshwaran Somasundaram[SUP] 1 [/SUP], Tod Steinfeld[SUP] 1 [/SUP], Lisha Wang[SUP] 1 [/SUP], Laura Wedel[SUP] 1 [/SUP], Samantha S Yim[SUP] 1 [/SUP], Li Yin[SUP] 1 [/SUP], Jiayi Zhou[SUP] 1 [/SUP], Zach Newby[SUP] 1 [/SUP], Winston Tse[SUP] 1 [/SUP], Johannes Grosse[SUP] 1 [/SUP], Herbert W Virgin[SUP] 1 [/SUP], Seungmin Hwang[SUP] 1 [/SUP], Amalio Telenti[SUP] 1 [/SUP]
Affiliations
- PMID: 40372436
- DOI: 10.1073/pnas.2414202122
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.
Keywords: CRISPR; functional genomics; genome-wide; host-directed therapy; respiratory virus.