N-myristoyltransferase Inhibitors as Candidate Broad-Spectrum Antivirals to Treat Viral Infections Promoted by Immunosuppression Associated with JAK Inhibitors Therapy

The use of Janus kinase (JAK) inhibitors in the clinic has been expanded significantly during the last decade. However, the immunosuppressive effects of JAK inhibitors, via modulation of key innate cellular signaling pathways, can predispose treated patients to infections, and can also result in reduced control of silent infections and increased risk of reactivation of opportunistic infections. Thus, the JAK inhibitor ruxolitinib, approved for the treatment of myelofibrosis and polycythemia vera, has been shown to exerts a proviral activity during infection with different viruses. Therefore, the clinical relevance of developing antiviral treatments that can be effective in the presence of JAK inhibitors. N-terminal myristoyl transferase (NMT) inhibitors have been shown to exhibit potent antiviral activity against different viruses. Here we document that in the presence of ruxolitinib, NMT inhibitors retain their potent antiviral activity against different viruses, including HSV-1. Our findings support that NMT inhibitors should be explored as therapeutics to treat viral infections associated with immunosuppression caused by treatments with JAK inhibitors.