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Cellular host factors for SARS-CoV-2 infection

Baggen et al., Nature Microbiology, doi:10.1038/s41564-021-00958-0, Sep 2021
https://c19early.org/baggen.html
Review of cellular host factors required for SARS-CoV-2 infection. Authors systematically examine proviral host factors that SARS-CoV-2 depends on for successful replication, identified through genome-wide CRISPR screens and viral interactome analyses.
Baggen et al., 1 Sep 2021, multiple countries, peer-reviewed, 4 authors. Contact: dirk.daelemans@kuleuven.be.
Abstract: Review Article https://doi.org/10.1038/s41564-021-00958-0 Cellular host factors for SARS-CoV-2 infection Jim Baggen , Els Vanstreels , Sander Jansen and Dirk Daelemans ✉ 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. C oronaviruses are positive-strand RNA viruses belonging to the subfamily Orthocoronavirinae within the family Coronaviridae (International Committee on Taxonomy of Viruses) and are subdivided into four genera—Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. Coronaviruses cause intestinal and respiratory infections in a variety of birds and mammals, including livestock and domestic animals. Seven human coronaviruses (HCoVs) have been characterized, four of which cause mild respiratory infections (HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1). The emergence of two highly pathogenic betacoronaviruses in 2002 (severe acute respiratory syndrome coronavirus (SARS-CoV)) and 2012 (Middle East respiratory syndrome coronavirus (MERS-CoV)) revealed that new pathogenic coronaviruses can emerge in the human population by zoonotic transmission (reviewed in ref. 1). In late 2019, a pathogenic coronavirus SARS-CoV-2 was first detected in Wuhan, China, causing an outbreak of severe pneumonia. This human pathogen is thought to have originated in horseshoe bats and was probably transmitted to humans through an intermediate host that remains to be identified2. Owing to its high contagiousness and the occurrence of asymptomatic carriers, SARS-CoV-2 rapidly spread across the globe and continues to claim human lives and obstruct social and economic activity, while vaccination programs are ongoing. The pandemic has prompted countless efforts to develop vaccines and antiviral therapies, but also many fundamental studies to better understand coronavirus biology. As cellular proviral host factors are potential antiviral drug targets, numerous studies have analysed host factor dependencies of coronaviruses, in particular SARS-CoV-2. In this Review, we provide an overview of proviral host factors for SARS-CoV-2. After explaining the coronavirus life cycle, we discuss the cellular receptors and proteases that are required for SARS-CoV-2 entry. As only few of the identified proviral host factors have been..
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