1. Academic Validation
  2. The Pan-ErbB tyrosine kinase inhibitor afatinib inhibits multiple steps of the mammarenavirus life cycle

The Pan-ErbB tyrosine kinase inhibitor afatinib inhibits multiple steps of the mammarenavirus life cycle

  • Virology. 2022 Sep 26;576:83-95. doi: 10.1016/j.virol.2022.09.005.
Keita Mizuma 1 Ayako Takashima 1 Beatrice Cubitt 2 Juan C de la Torre 2 Masaharu Iwasaki 3
Affiliations

Affiliations

  • 1 Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • 2 Department of Immunology and Microbiology, Scripps Research, La Jolla, CA, USA.
  • 3 Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, Japan. Electronic address: miwasaki@biken.osaka-u.ac.jp.
Abstract

The mammarenavirus Lassa virus (LASV) causes a life-threatening acute febrile disease, Lassa fever (LF). To date, no US Food and Drug Administration (FDA)-licensed medical countermeasures against LASV are available. This underscores the need for the development of novel anti-LASV drugs. Here, we screen an FDA-approved drug library to identify novel anti-LASV drug candidates using an infectious-free cell line expressing a functional LASV ribonucleoprotein (vRNP), where levels of vRNP-directed reporter gene expression serve as a surrogate for vRNP activity. Our screen identified the pan-ErbB tyrosine kinase inhibitor afatinib as a potent inhibitor of LASV vRNP activity. Afatinib inhibited multiplication of lymphocytic choriomeningitis virus (LCMV) a mammarenavirus closely related to LASV. Cell-based assays revealed that afatinib inhibited multiple steps of the LASV and LCMV life cycles. Afatinib also inhibited multiplication of Junín virus vaccine strain Candid#1, indicating that afatinib can have Antiviral activity against a broad range of human pathogenic mammarenaviruses.

Keywords

Afatinib; Antiviral; Arenavirus; ErbB; Junín virus; LCMV; Lassa virus; Replication; Transcription.

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