Delivering Safe, Trustworthy Medicines for Children ーInside SHIONOGI’s RSV Drug Discoveryー

“I want to deliver medicines that children can take with confidence,” says Atsuko Yamamoto of SHIONOGI’s Drug Discovery Research Organization, Disease Research Institute.

Respiratory syncytial virus (RSV) infection poses a high risk of severe illness in infants and older adults, yet no effective antiviral treatments are currently available. In clinical practice, RSV remains a significant “unmet medical need.” Aiming to address this challenge, Yamamoto engages in research every day.

— The name “RSV” may not be familiar to some readers. What kind of virus is it?

Yamamoto: RSV is extremely common: almost all children are infected at least once by the age of two, and reinfections occur repeatedly thereafter. In infants and older adults, it can cause serious respiratory symptoms and, at times, be life-threatening.

In recent years, wider availability of diagnostic kits has led to more confirmed diagnoses, and among families with small children, awareness of “RSV infection” has increased.

— How is it different from an ordinary cold?

Yamamoto: In newborns and infants in particular, RSV infection often leads to lower respiratory tract inflammation such as bronchiolitis or pneumonia, and it can sometimes become severe. Internationally, the disease is widely recognized as a major cause of hospitalization, on a par with influenza.

There are also reports that children who contract RSV are more likely to develop asthma later on. For families, hospitalizations and clinic visits create a substantial burden, including constant caregiving. All of these reasons are why effective treatments are needed.

— So it isn’t just a transient infection; it can also be linked to later asthma. That’s concerning. What treatment options exist?

Yamamoto: For RSV, there are preventive options such as vaccines and antibody therapies, but there are no effective antiviral treatments. As a result, this remains an area with significant unmet medical needs.

As a company committed to “liberating people from the threat of infectious diseases,” SHIONOGI launched an RSV drug discovery program out of a strong sense of mission to deliver an effective RSV treatment to society.

In fact, my own child developed RSV pneumonia at one year old and was hospitalized. Experiencing the distress of a non-verbal child, along with the exhaustion of a family keeping vigil at the hospital bedside, strengthened my determination to act—and that conviction continues to drive my research.

Yamamoto: We are advancing research and development on a candidate compound (S-337395) for RSV treatment. This compound employs a novel mechanism: it inhibits the “L protein,” which is essential for RSV replication.

“Based on prior experience developing antivirals, we believed that targeting a site essential for viral replication would be effective. For this project, we focused on the L protein,” says Yamamoto.

— You first handle research at the cellular and enzymatic levels. Where are the biggest challenges you have faced?

Yamamoto: The most memorable task was preparing large quantities of RNP (ribonucleoprotein)—a complex of RSV L protein and RNA—from cells infected with the virus during assay evaluation. Even small changes in infection timing or cell processing could dramatically alter the results, so it was difficult to optimize conditions.

We started with small trials as a team, and, once we validated the results, we scaled up—steady, incremental work. It’s demanding, but the hands-on process of generating results is also the essence of research.

— How is development progressing now?

Yamamoto: Clinical trials are underway, and the U.S. Food and Drug Administration (FDA) has granted the program “Fast Track” designation. This system is designed to expedite the development and review of new drugs for serious conditions, and I believe it reflects the high level of societal expectation for an RSV treatment.

Fast Track designation: A program established to facilitate development and expedite the review of drugs intended to treat serious conditions and to address unmet medical needs.

— You’re leading the team today. Could you tell us about your career path?

Yamamoto: I first researched metabolic diseases after joining SHIONOGI. After one year of childcare leave, I transferred to the infectious diseases group—right when the RSV drug discovery program was starting. Compared to the chronic diseases I’ve handled before, infectious disease research moves very quickly, with evaluation results visible in short timeframes, and that pace is very exciting.

Before the transfer, I had no background in virology or related research, so I was anxious about taking on the role. But my colleagues were incredibly supportive and taught me patiently whenever I had any questions.

In SHIONOGI’s R&D organization, researchers with different backgrounds openly teach and help one another. I’ve also made a point of explaining things carefully to others. That culture lets us reach our shared goal—new medicines—more quickly.

Currently, employees generally return to the same department after childcare leave.

— Your eagerness to learn, combined with the support of those around you, has sustained your 20-year career as a researcher. You’re a reassuring role model for future colleagues.

Yamamoto: As an infectious-disease-focused company, we all understand just how susceptible children are to infections (laughs). We also have systems that support work-life balance, making it easier to combine parenting and research work.

Also, experiences at home can inform your work. As I mentioned, soon after I returned from childcare leave, my child suffered from RSV infection, and I experienced the challenge of staying at the hospital bedside. That experience deepened my commitment to R&D even further.

This project isn’t just about making a drug; it’s about protecting patients’ lives and families’ daily living—as well as delivering a “healthy, fulfilling life” to society as a whole.

— What lies ahead for RSV drug discovery?

Yamamoto: Research on RSV therapeutics is proceeding step by step. Ultimately, we aim—carefully and deliberately—to extend development to the very populations we most want to help: children and older adults.

For SHIONOGI, an RSV therapeutic is a potential “third pillar” in acute respiratory infections, alongside treatments for COVID-19 and influenza. To ensure a medicine is widely accepted by society, we must rigorously confirm its safety and efficacy and advance one step at a time.

Drug discovery is never a solo endeavor. It’s about standing together with many colleagues to tackle societal challenges, and doing work that can save someone’s life.

For the smiles of children and their families in the future, we will keep moving forward together and continue to embrace this challenge.