Fluorescence imaging is one of the most powerful techniques for visualizing the distribution and function of biomolecules in living organisms. Although many small-molecule fluorescent probes have been developed, probes that can be utilized for in vivo imaging are still urgently needed. One of the biggest barriers to in vivo imaging, particularly when using small-molecule probes, is the difficulty of delivering the probes specifically to the target cells or tissues. In addition, the probes require a specific sensing ability to visualize the function of the target cells. To analyze the osteoclast function in vivo, recent studies have proposed the use of bisphosphonates (BPs), a class of drugs that contains effective bone-targeting functional groups. Furthermore, acidification during bone resorption is one of the distinctive features of these cells and could therefore also be targeted to visualize osteoclast-specific activity. In this review, the latest information about designing probes that would allow the visualization of osteoclast functions is summarized, including bone-targeting functional groups, as well as the recent developments in intravital imaging of osteoclast activity and motility.

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Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has high genomic similarity to SARS-CoV-1, which was responsible for SARS in 2003. Since 3C-like protease (3CL^pro) of these pathogenic coronaviruses processes functional proteins essential for the viral life cycle, it has been a viable target for drug development. YH-53 was originally developed as an anti-SARS agent, which would also inhibit 3CL^pro of SARS-CoV-2. In order to lead optimal inhibitors as anti-COVID-19 agents, we analyzed the bound structures of SARS-CoV-2 3CLpro with YH-53 or related compounds by computational docking along with the predictions of their pharmacokinetic properties and toxicities (ADMET). Under a covalent bond with 3CL^pro, YH-53 was found to bind to the enzyme in a correct docking pose so that each P subsite could bind to the corresponding S subsite of 3CL^pro. The blind docking of related compounds suggested that the P3 subsite of YH-53 was required for correct docking, while P1' was not so necessary. Some of the predicted ADMET properties of YH-53 were unfavorable, where the main contributors were large molecular weight and low solubility. Since P1' acts as a reactive warhead and P3 affects the substrate specificity, there may be a trade-off between the modification of substructures of YH-53 and the improvement of its ADMET properties. Based on these results, we propose plausible inhibitory candidates against SARS-CoV-2 with better ADMET qualities.

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