Lidocaine inhibits influenza a virus replication by up-regulating IFNα4 via TBK1-IRF7 and JNK-AP1 signaling pathways

• DOI: 10.1016/j.intimp.2023.109706
• Publication Date: 2023-01-11T05:04:27Z
• Authors: Xueer Liu; Fengqing Zheng; Lu Tian; Tian Li; Zelin Zhang; Zhihui Ren; Xiaoxuan Chen; Weiqiang Chen; Kangsheng Li; Jiangtao Sheng
• Keywords: IRF7; CCL22

Influenza A viruses (IAV), significant respiratory pathogenic agents, cause seasonal epidemics and global pandemics in intra- interannual cycles. Despite effective therapies targeting viral proteins, the continuous generation of drug-resistant IAV strains is challenging. Therefore, exploring novel host-specific antiviral treatment strategies urgently needed. Here, we found that lidocaine, widely used for local anesthesia sedation, significantly inhibited H1N1(PR8) replication macrophages. Interestingly, its effect did not depend on inhibition voltage-gated sodium channels (VGSC), main target lidocaine anesthesia. Lidocaine upregulated early IFN-I, interferon α4 (IFNα4) mRNA, protein levels, but those IFNβ mouse RAW 264.7 cell line human THP-1 derived Knocking out IFNα4 by CRISPR-Cas9 partly reversed lidocaine's PR8 Mechanistically, activating TANK-binding kinase 1 (TBK1)-IRF7 JNK-AP1 signaling pathways. These findings indicate has an incredible potential enhancing IFN-I In conclusion, our results auxiliary role anti-influenza virus therapy even anti-SARS-CoV-2 therapy, especially absence a specific medicine.