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Updated: Nov 25, 2025
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses
Ruofan Wang1, Camille R Simoneau2, Jessie Kulsuptrakul1
1Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Abstract:
The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E), and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.
Insights
Researchers identified common host factors like phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis that support infection by multiple coronaviruses, including SARS-CoV-2. Targeting these pathways offers a strategy for developing broad-spectrum antiviral therapies against coronavirus pandemics.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Coronaviridae cause a spectrum of human diseases, from mild respiratory illness to severe acute respiratory distress syndrome.
- Identifying shared host factors across diverse coronaviruses is crucial for developing broad-spectrum antiviral therapies against pandemics.
Purpose of the Study:
- To identify host factors essential for the replication of SARS-CoV-2 and common cold coronaviruses (OC43, 229E).
- To explore potential host-directed therapeutic targets against multiple coronaviruses.
Main Methods:
- Genome-wide CRISPR screens were performed on cells infected with SARS-CoV-2, OC43, and 229E.
- Viral entry factors and host pathways supporting viral replication were analyzed.
Main Results:
- Distinct entry factors were confirmed: ACE2 for SARS-CoV-2, aminopeptidase N for 229E, and glycosaminoglycans for OC43.
- Phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis were identified as critical host pathways for all three viruses.
- TMEM106B was identified as a host factor specifically supporting SARS-CoV-2 infection.
Conclusions:
- Host phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis are essential for the replication of diverse coronaviruses.
- Pharmacological inhibition of these pathways effectively reduced viral replication.
- These findings provide insights into the coronavirus life cycle and support the development of host-directed therapies.
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