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Lidocaine inhibits influenza a virus replication by up-regulating IFNα4 via TBK1-IRF7 and JNK-AP1 signaling pathways.
Liu, Xueer; Zheng, Fengqing; Tian, Lu; Li, Tian; Zhang, Zelin; Ren, Zhihui; Chen, Xiaoxuan; Chen, Weiqiang; Li, Kangsheng; Sheng, Jiangtao.
  • Liu X; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China.
  • Zheng F; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China.
  • Tian L; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China.
  • Li T; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China.
  • Zhang Z; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China.
  • Ren Z; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China.
  • Chen X; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China.
  • Chen W; Department of Neurosurgery, First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou 515041, Guangdong, China. Electronic address: wqchen@stu.edu.cn.
  • Li K; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China. Electronic address: ksli2013@yeah.net.
  • Sheng J; Department of Microbiology and Immunology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou 515041, Guangdong, China. Electronic address: jtsheng@stu.edu.cn.
Int Immunopharmacol ; 115: 109706, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2179732
ABSTRACT
Influenza A viruses (IAV), significant respiratory pathogenic agents, cause seasonal epidemics and global pandemics in intra- and 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 is urgently needed. Here, we found that lidocaine, widely used for local anesthesia and sedation, significantly inhibited H1N1(PR8) replication in macrophages. Interestingly, its antiviral effect did not depend on the inhibition of voltage-gated sodium channels (VGSC), the main target of lidocaine for anesthesia. Lidocaine significantly upregulated early IFN-I, interferon α4 (IFNα4) mRNA, and protein levels, but not those of early IFNß in mouse RAW 264.7 cell line and human THP-1 derived macrophages. Knocking out IFNα4 by CRISPR-Cas9 partly reversed lidocaine's inhibition of PR8 replication in macrophages. Mechanistically, lidocaine upregulated IFNα4 by activating TANK-binding kinase 1 (TBK1)-IRF7 and JNK-AP1 signaling pathways. These findings indicate that lidocaine has an incredible antiviral potential by enhancing IFN-I signaling in macrophages. In conclusion, our results indicate the potential auxiliary role of lidocaine for anti-influenza A virus therapy and even for anti-SARS-CoV-2 virus therapy, especially in the absence of a specific medicine.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza A virus / Interferon Type I / Influenza, Human / Influenza A Virus, H1N1 Subtype / COVID-19 Limits: Animals / Humans Language: English Journal: Int Immunopharmacol Journal subject: Allergy and Immunology / Pharmacology Year: 2023 Document Type: Article Affiliation country: J.intimp.2023.109706

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza A virus / Interferon Type I / Influenza, Human / Influenza A Virus, H1N1 Subtype / COVID-19 Limits: Animals / Humans Language: English Journal: Int Immunopharmacol Journal subject: Allergy and Immunology / Pharmacology Year: 2023 Document Type: Article Affiliation country: J.intimp.2023.109706