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Virology

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

Published:1 November 2022 DOI: 10.1016/j.virol.2022.09.005 PMID: 36183499
Keita Mizuma , Ayako Takashima , Beatrice Cubitt , Juan C. de la Torre , Masaharu Iwasaki

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.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Afatinib dimaleate 850140-73-7 C28H29ClFN5O7 378 suppliers $8.00-$2200.00
Afatinib dimaleate 850140-73-7 C28H29ClFN5O7 378 suppliers $8.00-$2200.00
Afatinib dimaleate 850140-73-7 C28H29ClFN5O7 378 suppliers $8.00-$2200.00
Afatinib dimaleate 850140-73-7 C28H29ClFN5O7 378 suppliers $8.00-$2200.00
Afatinib (diMaleate) 850140-73-7 - Inquiry
Afatinib (diMaleate) 850140-73-7 - Inquiry
BIBW2992 DiMaleate 850140-73-7 - Inquiry
BIBW2992 DiMaleate 850140-73-7 - Inquiry

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