Scientists at Scripps Research conducted a comprehensive siRNA screen that pinpointed key human host proteins exploited by SARS-CoV-2 during various infection stages. The study revealed 59 essential proteins supporting early and late viral replication phases, including extracellular matrix components like perlecan, which binds directly to the viral spike protein. These findings enable the strategic development of pan-coronavirus therapeutics targeting host factors, potentially overcoming issues of viral mutations and drug resistance. This shifts the paradigm from targeting viral components alone to focusing on critical human cellular pathways.