ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has claimed millions of lives and caused a global economic crisis. No effective antiviral drugs are currently available to treat infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The medical need imposed by the pandemic has spurred unprecedented research efforts to study coronavirus biology. Every virus depends on cellular host factors and pathways for successful replication. These proviral host factors represent attractive targets for antiviral therapy as they are genetically more stable than viral targets and may be shared among related viruses. The application of various 'omics' technologies has led to the rapid discovery of proviral host factors that are required for the completion of the SARS-CoV-2 life cycle. In this Review, we summarize insights into the proviral host factors that are required for SARS-CoV-2 infection that were mainly obtained using functional genetic and interactome screens. We discuss cellular processes that are important for the SARS-CoV-2 life cycle, as well as parallels with non-coronaviruses. Finally, we highlight host factors that could be targeted by clinically approved molecules and molecules in clinical trials as potential antiviral therapies for COVID-19.
Subject(s)
COVID-19/metabolism , SARS-CoV-2/physiology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Host-Pathogen Interactions/drug effects , Humans , Peptide Hydrolases/metabolism , RNA, Viral/metabolism , Receptors, Virus/metabolism , SARS-CoV-2/drug effects , Viral Proteins/metabolism , Virus Internalization/drug effects , Virus Replication/drug effects , COVID-19 Drug TreatmentABSTRACT
The ongoing COVID-19 pandemic has caused a global economic and health crisis. To identify host factors essential for coronavirus infection, we performed genome-wide functional genetic screens with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E. These screens uncovered virus-specific as well as shared host factors, including TMEM41B and PI3K type 3. We discovered that SARS-CoV-2 requires the lysosomal protein TMEM106B to infect human cell lines and primary lung cells. TMEM106B overexpression enhanced SARS-CoV-2 infection as well as pseudovirus infection, suggesting a role in viral entry. Furthermore, single-cell RNA-sequencing of airway cells from patients with COVID-19 demonstrated that TMEM106B expression correlates with SARS-CoV-2 infection. The present study uncovered a collection of coronavirus host factors that may be exploited to develop drugs against SARS-CoV-2 infection or future zoonotic coronavirus outbreaks.