Seeking the Master Key to Conquer Pandemics

Although the COVID-19 pandemic has been officially declared over, the battle rages on at the forefront of research. Humanity has faced pandemics caused by a range of cross-species infectious viruses, including the Spanish flu a century ago, Ebola, Zika, SARS, MERS, and COVID-19. Alarmingly, the intervals between outbreaks are becoming shorter. This underscores the urgent need for proactive measures and researchers dedicated to preparing for the next pandemic.

In 2021, when it still seemed premature to think about the post-COVID-19 era, the Institute for Basic Science (IBS) established the Center for Study of Emerging and Re-emerging Viruses at the Korea Virus Research Institute. Its mission is to seek the master key to conquering pandemics. The team focuses on identifying the common “vulnerabilities” of emerging RNA viruses, such as SARS, MERS, and COVID-19, and targeting them effectively. This vision is being realized in part through research recently published in Science Signaling, a sister journal of Science.

Dr. KIM Hyun Joon, a senior researcher at the Center, introduces himself as an "organoid scientist." His goal is to leverage organoids, which are laboratory-grown organ models that facilitate safe infection experiments, to efficiently identify the master key to combating pandemics. He explains, "By establishing a comprehensive transcriptome and epitranscriptome database for various emerging viruses, we can also develop a 'pan-antiviral agent.' To this end, we are building a biobank of organoids that mimic over 20 types of animal and human organs."

Dr. Kim has a unique research background. Known as the “frog scientist,” he spent 20 years studying frog embryogenesis starting as an undergraduate. Later, under the guidance of a renowned RNA biologist Director KIM V. Narry of the IBS Center for RNA Research, he honed his expertise in RNA research. During this time, he contributed to the world’s first complete genetic map of COVID-19, gaining recognition in the scientific community. Now, Dr. Kim dreams of conquering pandemics through his cutting-edge research.

Q. Please introduce yourself.
Hello, I am Dr. KIM Hyun Joon, a senior researcher at the Center for Study of Emerging and Re-emerging Viruses, part of the Korea Virus Research Institute at IBS. I initially specialized in studying embryogenesis using frog embryos, a field I dedicated myself to for 20 years starting in 2003. After 2020, the onset of the COVID-19 pandemic shifted my focus to RNA viruses. Today, I use organoid models to study various RNA viruses, and I hope to be known as an "organoid scientist" moving forward.

Q. What does the Korea Virus Research Institute Center for Study of Emerging and Re-emerging Viruses do?
The Center focuses on identifying and conducting proactive research on emerging viruses that could trigger the next pandemic. It aims to establish a foundation for basic virus research by concentrating on virus surveillance, cellular replication mechanisms, and virus-induced diseases in animal models. Moreover, recognizing infectious diseases as a shared challenge for humanity, the Center collaborates closely with global research and policy institutions to enhance infectious disease security both in Korea and worldwide.
he Center operates a three-stage research system: identifying emerging viruses → studying cellular replication mechanisms → researching virus-induced diseases in animal models. This structure is optimized to strengthen basic research capabilities against unknown viruses.Having been launched with strong support from the government and the public, all members of the center are dedicated to contributing to global infectious disease security through fundamental virus research.

Q. What is your role at the Center as a senior researcher?
I focus on the second stage of the three-stage virus research system: basic research on the cellular replication mechanisms of emerging viruses. Using organoid models, I am working to establish a comprehensive transcriptome and epitranscriptome database for cross-species RNA viruses that infect both humans and animals.
Specifically, I collaborate with the institute’s Center for Genome Engineering to build a biobank of organoids that mimic over 20 types of organs from wild animals and humans, including the respiratory tract, lungs, kidneys, small intestine, liver, and mammary glands. These organoids are then used to identify and study various viruses and their characteristics. Ultimately, my goal is to utilize organoids as infection models to establish a complete transcriptome and epitranscriptome database for all cross-species RNA viruses.

Q. Why is virus research still important after the end of the COVID-19 pandemic?
Humanity has suffered from a range of cross-species infectious viruses, including the Spanish flu, Hong Kong flu, Ebola, HIV, dengue, Zika, SARS, MERS, and COVID-19, with outbreaks occurring more frequently. Even though the COVID-19 pandemic has ended, the need to study and monitor emerging viruses remains critical. Such research could also lead to the development of new antiviral treatments.

Q. We saw your recent research published in Science Signaling last month.
Coronaviruses, including COVID-19, continue to mutate and pose threats to humanity. This is because they constantly develop new mechanisms to invade host cells, making them resistant to vaccines and treatments. The paper we published last month identified that a biological enzyme called KLK5 plays a universally crucial role in the cellular invasion of various coronaviruses.
Our findings suggest that inhibiting KLK5’s function could effectively block not only existing coronaviruses but also unknown coronaviruses that may emerge in the future. This implies that an "anti-KLK5 agent" could serve as a proactive antiviral treatment for future pandemics. Currently, we are working in collaboration with domestic and international research institutions to discover and refine anti-KLK5 agents, aiming to develop effective drugs with minimal side effects.

Q. What motivated you to start this research?
I was intrigued by the phenomenon where the Omicron variant of COVID-19 exhibited reduced pathogenicity but increased transmissibility. I was also curious about the mechanism behind Omicron's greater resistance to existing antiviral agents for COVID-19. Although this study did not uncover the unique characteristics of the Omicron variant, we made a significant discovery regarding the importance of the KLK5 enzyme during the research process. As previously mentioned, we found that KLK5 plays a critical role in the cellular invasion of not only COVID-19 but also other coronaviruses such as SARS and MERS.

Q. Please share what led you to join the Center for Study of Emerging and Re-emerging Viruses.
I wanted to leverage my expertise in embryonic development and RNA research to conduct meaningful studies on RNA viruses. Since most viruses that have caused pandemics are RNA viruses, there’s a high likelihood that future pandemics will also be driven by them.
My previous experience has been highly beneficial for the research at the Center for Study of Emerging and Re-emerging Viruses. The embryonic development studies I conducted under my doctoral advisors, Professor HAN Jin-Kwan (former professor at POSTECH) and Professor De ROBERTIS (at UCLA), have translated into the use of organoid models. Similarly, the RNA research I conducted under Director KIM V. Narry has been directly applicable to studying RNA viruses.

Q. What are your future research plans?
We have established an organoid biobank with over 20 animal models as a research platform to discover various novel viruses and investigate their characteristics. Moving forward, we aim to study the characteristics of various heterologous RNA viruses using organoids, with the ultimate goal of establishing a comprehensive transcriptome and epitranscriptome database for viruses as a whole.

Q. What challenges do you face in your research?
Building the organoid biobank requires obtaining living tissues from a wide variety of animals in a single initial collection. We collaborate with leading institutions in Korea to acquire various animals, including wild species, and extract tissues to create organoids. However, due to the limited number of collection opportunities, it is often challenging to secure a diverse range of animal tissues.

Q. There must be government support measures that you think are necessary.
Collaborating with zoos to obtain tissues from animals that have died naturally or are near death would greatly aid the establishment of the organoid biobank. However, due to various animal-related laws, there are significant limitations in using zoo animals for research purposes. To overcome these constraints, it would be necessary to either relax the regulations or establish new systems specifically for infectious disease research. This requires substantial attention and support from the government, the National Assembly, and the public. I hope this interview helps garner interest and backing for our research moving forward.

Q. Artificial intelligence (AI), such as DeepMind’s AlphaFold, is playing an increasingly significant role in the field of life sciences. How are you preparing for this change as a researcher?
Korea has accumulated systematic and extensive disease data through its experience with the COVID-19 pandemic. I believe it is essential to develop AI models tailored to the unique characteristics of the country to make better use of this data. Personally, I actively incorporate AI models into my organoid research. I am collaborating closely with the BI team within the Center for Emerging and Re-emerging Viruses on joint studies. For example, we use AI models to analyze the characteristics of individual organoids by training them on immunostained images of organoid slices.

Q. Lastly, do you have any final remarks?
In front of the IBS headquarters, there is an inscription that reads, "Making Discoveries for Humanity & Society." Seeing these words always fills me with inspiration. I firmly believe that the basic science research conducted at IBS will not be about immediate economic gains but rather provide fundamental solutions to the challenges humanity faces—or will face in the future.
The same applies to infectious disease research. Even before a pandemic arises, there are people around the world conducting surveillance and proactive research. Their cumulative experiences and findings will serve as the driving force to overcome new pandemics. At the IBS Korea Virus Research Institute, we are diligently working with the goal of addressing the growing threats posed by viruses and infectious diseases, contributing to the biosecurity of Korea and humanity as a whole.