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

Mizuma, Keita; Takashima, Ayako; Cubitt, Beatrice; Torre, Juan Carlos de la; Iwasaki, Masaharu

doi:10.1016/j.virol.2022.09.005

Cited by 4 publications

(1 citation statement)

References 68 publications

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“…A requirement for ErbBs was documented in the entry and/or post-entry stages of multiple viruses (128). Several anticancer ErbB inhibitors, including gefitinib, demonstrate activity against HCV, human cytomegalovirus (HCMV), poxvirus, and Lassa virus in cultured cells (129)(130)(131)(132)(133), and CMV in guinea pigs (132). In human lung and brain organoid models of SARS-CoV-2 and VEEV infections, respectively, we have recently shown that, beyond suppressing viral replication, lapatinib, an anticancer pan-ErbB inhibitor, protects from virus-induced activation of pathways implicated in non-infectious tissue injury downstream of ErbBs, proinflammatory cytokine production, and epithelial or blood-brain barrier injury (98).…”

Section: Host-targeted Broad-spectrum Antiviral Approachesmentioning

confidence: 99%

Preparing for the next viral threat with broad-spectrum antivirals

Karim¹,

Lo²,

Einav³

2023

Journal of Clinical Investigation

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There is a large global unmet need for the development of countermeasures to combat hundreds of viruses known to cause human disease and for the establishment of a therapeutic portfolio for future pandemic preparedness. Most approved antiviral therapeutics target proteins encoded by a single virus, providing a narrow spectrum of coverage. This, combined with the slow pace and high cost of drug development, limits the scalability of this direct-acting antiviral (DAA) approach. Here, we summarize progress and challenges in the development of broad-spectrum antivirals that target either viral elements (proteins, genome structures, and lipid envelopes) or cellular proviral factors co-opted by multiple viruses via newly discovered compounds or repurposing of approved drugs. These strategies offer new means for developing therapeutics against both existing and emerging viral threats that complement DAAs.

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