Viral Infection and Establishing New Therapeutic Platforms– On the Occasion of Receiving the 16th Setsuro Ebashi Award –

During the past quarter century, a series of global pandemics—caused by coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and influenza A (H1N1, H5N1)—has underscored that viral infection is not merely a transient invasion but a systemic and temporal perturbation of the host life system. My research has sought to elucidate the principles by which the host organism senses, integrates, and regulates responses to viral stress, spanning molecular to organismal levels. Key discoveries include the identification of ACE2 as the functional receptor for SARS-CoV and a critical regulator of disease severity; elucidation of innate-immune overactivation (“cytokine storm”) as a driver of fatal pathology; identification of lipid-mediated RNA regulation that restrains excessive inflammation; and discovery of neuro-immune and epigenetic mechanisms linking acute infection to long-term dysfunction. These findings reveal infection as a multi-layered biological reprogramming process involving immunity, metabolism, the nervous system, and chromatin architecture. Building on this mechanistic foundation, we established data-driven infrastructures—AI-assisted predictive models and Medical MLOps systems—that integrate clinical and molecular data for personalized infection medicine. This perspective summarizes the evolution of this integrative research and discusses future directions toward precision therapeutics for acute and post-infectious syndromes. PrefaceIt is a great honor to have received the 16th Setsuro Ebashi Award, which recognizes outstanding contributions to life-science research in Japan. I am deeply grateful to the selection committee and to the many mentors and collaborators who have supported my scientific journey. The award bears the name of Professor Setsuro Ebashi, whose pioneering work on calcium signaling and muscle physiology opened new horizons in understanding dynamic life systems. Inspired by his legacy, my research has focused on elucidating how the host life system operates under viral infection stress and on developing novel therapeutic platforms grounded in this understanding.Over the past two decades, the world has repeatedly faced pandemics caused by coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) and influenza viruses (H1N1, H5N1). These outbreaks have demonstrated that viral infections are not transient or localized events, but systemic perturbations involving immune, metabolic, neural, and epigenetic networks.This perspective summarizes key milestones of our studies—from the identification of ACE2 as a viral receptor to the creation of AI-driven infection medicine—and reflects on how these discoveries have reshaped our understanding of host resilience and vulnerability to viral stress ( Figure 1 ).