Luciferase-Based Biosensors in the Era of the COVID-19 Pandemic

[Image: see text] Luciferase-based biosensors have a wide range of applications and assay formats, including their relatively recent use in the study of viruses. Split luciferase, bioluminescence resonance energy transfer, circularly permuted luciferase, cyclic luciferase, and dual luciferase systems have all been used to interrogate the structure and function of prominent viruses infecting humans, animals, and plants. The utility of these assays is demonstrated by numerous studies which have not only successfully characterized interactions between viral and host cell proteins but that have also used these systems to identify viral inhibitors. In the present COVID-19 pandemic, luciferase-based biosensors are already playing a critical role in the study of the culprit virus SARS-CoV-2 as well as in the development of serological assays and drug development via high-throughput screening. In this review paper, we provide a summary of existing luciferase-based biosensors and their applications in virology.