Proposing a new drug to treat tuberculosis utilizing state-of-the-art computer simulations

January 18, 2021

Overview:

The research team of the Department of Computer Science and Engineering at the Toyohashi University of Technology and the Institute of Food Biotechnology and Genomics at the National Academy of Sciences of Ukraine have proposed a new drug to treat tuberculosis (TB), utilizing the state-of-the-art molecular simulations. This drug may inhibit the cell division of Mycobacterium tuberculosis (M. tuberculosis) and suppress its growth. In addition, because this drug acts on the enzymes secreted by M. tuberculosis instead of acting on M. tuberculosis itself, M. tuberculosis has very little chance of mutation and develops no drug resistance. Therefore, it is expected that this drug will lead to a novel drug that will keep its effectiveness for a long time.

Details:

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 mutants have a possibility to retain a resistance against the existing drugs, resulting in making 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 the compound that binds more strongly to FtsZ as a new drug to treat TB.

Development Background:

Master's student and lead author of this 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, I answered that its structure was too complex and that it would be difficult to investigate 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."

Future Outlook:

Currently, we are requesting that the compound proposed in this paper 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. 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.
-end-
Reference:

"Design of potent inhibitors against bacterial cell-division protein FtsZ: molecular docking and ab initio molecular orbital calculations", Yamamoto, S.; Saito, R.; Nakamura, S.; Sogawa, H.; Karpov, P.; Shulga, S.; Blume, Y.; Kurita, N., Antibiotics, 2020, 9, 846; doi:10.3390/antibiotics9120846.

"Binding sites of Zantrin inhibitors to the bacterial cell division protein FtsZ: molecular docking and ab initio molecular orbital calculations", Sogawa, H.; Sato, R.; Suzuki, K.; Tomioka, S.; Shinzato, T.; Karpov, P.; Shulga, S.; Blume, Y.; Kurita, N., Chemical Physics, 2020, 530, 110603.

Toyohashi University of Technology (TUT)

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.