Scripps Research scientists performed a genome-wide siRNA screen to pinpoint essential human host proteins exploited by SARS-CoV-2 during its replication cycle. The study identified over 30 host factors critical in early infection stages and an additional 27 involved later, including novel pathways such as NADH oxidation and arachidonate production. Two key targets include the extracellular matrix protein perlecan, which binds viral spike protein. These findings support developing host-targeted pan-coronavirus therapies less susceptible to viral mutations.