[HTML][HTML] The Pan-ErbB tyrosine kinase inhibitor afatinib inhibits multiple steps of the mammarenavirus life cycle
K Mizuma, A Takashima, B Cubitt, JC de la Torre… - Virology, 2022 - Elsevier
K Mizuma, A Takashima, B Cubitt, JC de la Torre, M Iwasaki
Virology, 2022•ElsevierThe 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 …
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 …
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.
Elsevier