Suppressors of
Cytokine Signaling (SOCS) are intracellular
proteins that negatively regulate the induction of
cytokines. Amongst these, SOCS1 and SOCS3 are particularly involved in inhibition of various
interferons. Several viruses have hijacked this regulatory pathway: by inducing SOCS1and 3 early in
infection, they suppress the host immune response. Within the cell, SOCS1/3 binds and inhibits
tyrosine kinases, such as JAK2 and TYK2. We have developed a
cell penetrating peptide from the activation loop of the
tyrosine kinase, JAK2 (residues 1001-1013), denoted as pJAK2 that acts as a decoy and suppresses SOCS1 and 3 activity. This
peptide thereby protects against several viruses in cell culture and mouse models. Herein, we show that treatment with pJAK2 inhibited the replication and release of the beta coronavirus HuCoV-OC43 and reduced production of the
viral RNA, as measured by RT-qPCR, Western blot and by immunohistochemistry. We confirmed induction of SOCS1 and 3 in
rhabdomyosarcoma (RD) cells, and this induction was suppressed by pJAK2
peptide. A
peptide derived from the C-terminus of IFNα (IFNα-C) also inhibited replication of OC43. Furthermore, IFNα-C plus pJAK2 provided more potent inhibition than either
peptide alone. To extend this study to a pandemic beta-coronavirus, we determined that treatment of cells with pJAK2 inhibited replication and release of SARS-CoV-2 in Calu-3 cells. We propose that these
peptides offer a new approach to
therapy against the rapidly evolving strains of beta-coronaviruses.