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日本語

Currently, the global spread of COVID-19 caused by the novel coronavirus has become a major social issue. Similarly, TB caused by M. tuberculosis is also one of the most dangerous infectious diseases in the world to date, and various drugs used to treat TB have been developed. However, as the M. tuberculosis easily mutates, its new mutations can develop resistance to existing drugs, and thus rendering them ineffective. This fact is a major bottleneck to further development of TB drugs.

Therefore, to prevent the occurrence of this drug resistance, drugs that act on the enzymes secreted by M. tuberculosis instead of M. tuberculosis itself are being developed. In this research, we targeted the cytoskeletal protein FtsZ, which is essential for M. tuberculosis to perform cell division, and by inhibiting that function, we aimed to develop a new drug that inhibits the cell division of M. tuberculosis and suppresses its growth. For this purpose, we used the state-of-the-art and high-precision molecular simulation method developed by our research group to analyze the binding properties between FtsZ and the various compounds that are drug candidates. Based on the results simulated, we proposed a compound that binds more strongly to FtsZ as a new drug to treat TB.

Master’s student and lead author of this research paper, Shohei Yamamoto, reflects on that time below. "Because the FtsZ protein targeted in this research has many positions where compounds can bind to it, we had difficulty identifying the positions of the FtsZ protein in which the compounds considered as drug candidates would bind most strongly in the molecular simulation. I think that being able to solve this matter led to the proposal of a therapeutic drug for TB."

In addition, the research team’s leader, Associate Professor Noriyuki Kurita, recounts how the research began below. "This research is a collaboration with my old friends at the National Academy of Sciences of Ukraine. I remember about five years ago, when I visited a laboratory in Kyiv, Ukraine and was first introduced to a protein called FtsZ, my feeling then was that its structure was too complex to allow for investigation into its binding properties with drug-like compounds in our molecular simulations. However, my friends asked me several times to start the calculations, and finally our intimate collaboration study started. I think that Eastern European researchers tend to thoroughly pursue difficult research themes even if it takes a long time, and that there are many things that we could learn from how they proceed with their research."

Currently, we are requesting that the compound proposed in this research be synthesized in a Ukrainian laboratory and the effects be investigated by cell experiments, but due to the economic situation of the other party, it seems that this will take time to realize. In addition, the molecular simulation method used in this research can be applied to other proteins, and we are currently conducting calculations with the aim of proposing new inhibitors for the proteins of the novel coronavirus.

This research was carried out through an international internship program supported by the Japan Student Services Organization (JASSO), student exchange and research exchange programs between the Toyohashi University of Technology and the Institute of Food Biotechnology and Genomics at the National Academy of Sciences of Ukraine, and a joint research program. We would like to thank Professor Yaroslav Blume, Professor Sergey Shulga, and Doctor Karpov Pavel of the National Academy of Sciences of Ukraine for providing valuable information in advancing this joint research.