Genome-wide analysis of host-encoded microRNAs modulating SARS-CoV-2 infection

Abstract

Viruses exploit cellular machinery to complete their replication cycle. Furthering our understanding of this process provides insight into the mechanism of virus replication and potential targets for antiviral therapeutics. Genome-wide CRISPR screens have identified cellular pathways important in the SARS-COV-2 infection process, including vesicular traffic, lipid homeostasis and PI3K signalling. Functional genomics-driven analysis of host-encoded microRNAs (miRNAs) impacting SARS-CoV-2 infection would provide further unbiased and discovery-driven insight into the host-pathogen interface. Here we present findings from genome-wide complementary miRNA mimic and inhibitor screens performed in a bio-safety level (BSL)-4 laboratory using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines. This dataset has identified both miRNA promoters and inhibitors of SARS-CoV-2 replication which may be used by researchers to further explore therapeutic targets against SARS-CoV-2 and the host factors influencing COVID pathogenesis.