Recent virological researches using biophysical methods, termed as virus biophysics or virophysics, largely contribute to the development of anti-viral drugs and vaccines. In this review, examples of structural and physicochemical analyses for representative viruses to develop drug modalities such as small compounds, antibodies, and vaccines are explained, and future direction of biophysical research for virus research is also discussed.

Influenza virus is a respiratory pathogen that causes pandemics and seasonal epidemics. The pathophysiological changes and in vivo dynamics of immune cells in influenza virus-infected lungs are poorly understood. Here, we established an in vivo imaging system that combines two-photon excitation microscopy and fluorescent influenza viruses of different pathogenicity. This approach allowed us to monitor and correlate several parameters and pathophysiological changes in the lungs of live mice. Our findings demonstrate the potential of this in vivo imaging system, which we termed two-photon IMPRESS (IMaging Pathophysiology RESearch System), to provide novel information about the pathophysiological consequences of influenza virus infection.

Digital assays, which have evolved from single-molecule detection technology, are attracting attention as a new method of measuring individual cells, proteins, and nucleic acids. The digital assays are characterized by their ability to directly measure individual molecules, enabling us to perform absolute quantification without the need for calibration curves and to determine the heterogeneity of a population. We first developed a digital assay for enzymes and applied the principle to digital ELISA and digital influenza assays. We demonstrate that the digital assays for enzymes are not only a new enzymology tools, but also have a wide range of applications such as elucidating the nature of viral populations. We will discuss how these new analytical techniques are opening up uncharted territory.

The novel coronavirus disease (COVID-19) pandemic has emerged in late 2019 and rapidly spread all over the world. In order to assist structure-based discovery efforts for repurposing drugs against the infectious disease, we constructed homology models of SARS-CoV-2 proteins. We identified several potential drugs by comparing the ligand molecules in the template structures with approved or experimental drugs and compounds of natural drugs, including carfilzomib, sinefungin, tecadenoson, and trabodenoson, that would be further investigated for their potential for treating COVID-19.