Redirecting the JAK‐STAT signal blocks the SARS‐CoV‐2 replication

Abstract

AbstractThe distinct disease progression patterns of severe acute respiratory syndrome coronavirus clade 2 (SARS‐CoV‐2) indicate diverse host immune responses. SARS‐CoV‐2 severely impairs type I interferon (IFN) cell signaling, resulting in uncontrolled late‐phase lung damage in patients. For better pharmacological properties, cytokine modifications may sometimes result in a loss of biological activity against the virus. Here, we employed the genetic code expansion and engineered IFN‐β, a phase II clinical cytokine with 3‐amino tyrosine (IFN‐β‐A) that reactivates STAT2 expression in virus‐infected human cells through JAK/STAT cell signaling without affecting signal activation and serum half‐life. This study identified that genetically encoded IFN‐β‐A might stabilize the protein‐receptor complex and trigger JAK‐STAT cell signaling, which is a promising modality for controlling SARS‐CoV‐2 infection.