Why do some people with COVID19 get sicker than others? Although many factors govern how sick people become, a key driver of the severity appears to be genetic, which is common for other human viruses. Learn more in a recent SciencePerspective:
) show that susceptibility to severe COVID-19 is associated with a single-nucleotide polymorphism in the human gene 2′-5′-oligoadenylate synthetase 1 .
OAS1 is an enzyme that is activated in the presence of double-stranded RNA, which is scattered along an otherwise singlestranded SARS-CoV-2 genome because of an assortment of RNA hairpins and other secondary structures. Once activated, OAS1 catalyzes the polymerization of adenosine triphosphate into a second messenger, 2′-5′-oligoadenylate. This then triggers the conversion of ribonuclease L into its active form so that it can cleave viral RNA, effectively blunting viral replication .
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