Apart from preventing interferon production, CoV proteins have also evolved to suppress interferon effector signalling. One of the best-characterized examples is the oligoadenylate synthetase (OAS)-RNase L pathway. Upon activation by interferon in response to the sensing of dsRNA, transcription and expression of OAS are induced to catalyse 2′,5′-oligoadenylate (2′-5′A) synthesis [65]. 2′-5′A serves as a second messenger, which activates RNase L and limits viral replication through the cleavage of cellular and viral single-stranded RNA [65]. The cleaved RNA fragments, in turn, prime RNA sensors to amplify interferon production in infected cells. To counter RNase L activity, some CoVs have evolved phosphodiesterases which cleave 2′-5′A [66]. The first CoV phosphodiesterase identified is NS2a in mouse hepatitis virus. From protein sequence alignment, multiple CoVs including NS2a from OC43 and a bat CoV, as well as ORF4b encoded by MERS-CoV, are very similar to NS2a of mouse hepatitis virus. All these viral proteins preserve a phosphodiesterase activity [67]. This suggests that some CoVs have developed an important enzymatic activity through convergence and divergence. Hence, although most HCoVs retain one or another strategy to counter host antiviral defence, the highly pathogenic CoVs are particularly powerful in the suppression of host immunity. These capabilities might be weakened or lost when they adapt to humans.