URP
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Repurposed Drugs Present New Strategy for Treating COVID-19
Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates
A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3.
Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives.
The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds.
The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected.
“We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn’t resolve the toxicity issues in preclinical trials,” said Woo Dae Jang, one of the researchers from KAIST.
“The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus,” said Distinguished Professor Sang Yup Lee.
This work was supported by the KAIST Mobile Clinic Module Project funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF). The National Culture Collection for Pathogens in Korea provided the SARS-CoV-2 (NCCP43326).
-PublicationWoo Dae Jang, Sangeun Jeon, Seungtaek Kim, and Sang Yup Lee. Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay. Proc. Natl. Acad. Sci. U.S.A. (https://doi/org/10.1073/pnas.2024302118)
-ProfileDistinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr
Department of Chemical and Biomolecular EngineeringKAIST
2021.07.08 View 10740 -
Undergrad's Paper Chosen as the Cover Article in Soft Matter
(from left: Research Professor KyuHan Kim and Undergrad Student Subeen Kim)
A KAIST undergraduate student, Subeen Kim, had his paper chosen as the cover article in an international journal during his senior year.
There have been an increasing number of undergraduate students who were published as the first author because the KAIST Undergraduate Research Participation program allows more active research participation by undergraduate students.
Through URP, Kim successfully published his paper in the internationally-renowned journal, Soft Matter, which is published by the Royal Society of Chemistry, and it was chosen as the cover article of that journal in February 2018.
This publication means a lot to him because he designed the cover image himself, based on his imagination and observations.
His research is about controllable one-step double emulsion formation. Double emulsion is a system in which dispersed droplets contain additional immiscible liquid droplets.
Having great retention ability, double emulsion has been used in various applications in the food industry, in cosmetics, and for drug delivery. Nevertheless, two-step emulsification is a conventional approach to produce double emulsions that typically leads to partial destabilization of the emulsion formed during the initial stage. Hence, it does not ensure the stability of a double emulsion. On the other hand, a microfluidic approach with various flow-focusing techniques has been developed, but it has low production efficiency and thus limited industrial applications.
Kim’s results came from the process of phase inversion to solve this problem. He identified the instant formation of double emulsions during the process of phase inversion. Based on this finding, he proposed criteria to achieve high stability of double emulsion.
Through constant research, he developed a quite general method using a combination of an oil soluble poly methyl methacrylate (PMMA) and hydrophobic silica nanoparticle (HDK H18). This new method enables one-step and stable production of double emersions in a stable manner. It also allows control of the number and the volume of inner oil droplets inside the outer water droplets by adjusting PMMA and HDK H18.
Kim enrolled at KAIST as a KAIST Presidential Fellowship and Presidential Science Scholarship in 2014. While studying both chemical and biomolecular engineering and chemistry he has been developing his hypothesis and conducting research.
He was able to begin conducting research because he has taken part in URP projects twice. In his sophomore year, he studied the formation of high internal phase double emulsions. After one year, he conducted research to produce superabsorbent resins, which are the base material for diapers, by using colloid particles. Using partial research outcomes, he published his paper in Nature Communications as a second author.
Kim said, “Double majoring the chemical and biomolecular engineering and chemistry has helped me producing this outcome. I hope that this research contributes to commercializing double emulsions. I will continue to identify accurate principles to produce chemicals that can be controlled exquisitely.”
Figure 1. The cover article of Soft Matter
2018.05.03 View 9277 -
KAIST Holds Its Fourth Public Art Exhibition
KAIST hosted an opening ceremony for the annual art exhibition on December 3, 2015 at the KAIST Institute building. The KAIST Art and Design Committee first organized the event in 2012 to promote the integration of art and technology.
This year’s event entitled “Understanding the Purpose of an Object” will display 20 art pieces under six themes. Artist Keumhong Lee, Haeyool Roh, Joon Kim, Kyung Lee, and Juhae Yang participated in the exhibition. The names of some of the art pieces include “Feedback Field” by Joon Kim, “Self Action” by Haeyool Roh, and “Net of Time” by Juhae Yang.
Juhae Yang believes that, in the digital age, an identity of an object is defined by the traces of light which we read in the information hidden in the barcodes. Based on this interpretation, she transforms the black bars and white spaces into a harmony of colors and sounds. The continuum of colors and sounds in her work arouses time-space synesthesia.
Professor Sangmin Bae of the Industrial Design Department, the Director of the KAIST Art and Design Committee, hopes that the exhibition will inspire novel scientific ideas and artistic spirits.
The exhibition will remain open to the public until December 20, 2015.
2015.12.03 View 7368 -
A Volunteer Project by Students: The Surprise Bus!
GoGeeks, one of the undergraduate student clubs at KAIST, plans to run a bus to take volunteers to places where help is needed such as nursing homes, orphanages, and community centers. This volunteer project is called “Surprise Bus!” Students interested in participating in the project can apply online via a social funding website, http://tumblbug.com, until December 5, 2014. Up to 150 students will be selected.
A total of five buses will leave from Seoul on December 20, 2014 to several places nationwide. Participants will not know their final destination until they arrive at the scene where they will work. GoGeeks was inspired by the “Do Good Bus” project, a volunteer organization that started in the US, through which people meet, and while performing their volunteer activities, they get to know each other.
Bum-Kyu Lee, the President of GoGeeks, who is a senior in the Department of Industrial and Systems Engineering, said, “I’ve encountered many students who want to volunteer, but they are not sure where to go to start. The “Surprise Bus!” is a wonderful volunteer opportunity, and I think participants will have fun and, at the same time, will have a meaningful time. The Christmas season is also an excellent time to do something good for our communities and neighborhoods.”
2014.12.04 View 7344 -
Undergraduate Research Program, Putting Wings on Undergraduate"s Dreams
KAIST held the 2011 URP Research Result Presentation in the Creative Learning Center on the 17th. Four students Jae Gyung Seo, Tran An Tu, Gun Sik Ahn, and Gyung Ryul Bong have been chosen as the grand prize winners.
The grand prize winners receive 3.5million won to allow them to participate in an international academic conference. The URP program is the first of its kind in Korea and has been benchmarked from MIT’s UROP(Undergraduate Research Opportunity Program).
The school selects 60 individual and 20 team research projects for undergraduates twice a year and provides mentorship as well as financial support.
Students signing up for the URP are to submit research plans and are then chosen through looking at these documents. Students receive 6 months of research funds and are to work under a professor and TA in groups of 2 to 3 or individually.
The URP program which is funded by the Ministry of Science and Technology has settled in successfully and has been expanded to the entire country.
The head of the R&D team, Yong Jae Sung, stated, “The number of research plans have been 154 in 2008, 189 in 2009, 220 and 251 respectively in 2010 and 2011. It’s continuously rising. And over 80% of responses on satisfaction surveys have replied that students were satisfied. It is very popular among undergraduates.“
Student Sang Yeon Cho has also said, “I was able to research on everything that I wanted under funding of the school and the guidance of renowned professors thanks to the URP program.”
To Seul Gi Lee, a graduate student for the electrical engineering department who has developed the wearable sleeping pattern analysis system, URP is an especially special program.
She said, “I successfully researched in the wearable health care field as my URP research material in 2006 when I was in my junior year. I made second place. After this, I have continued my research in this field on SoC(System on Chip) for wearable healthcare in graduate school and will be receiving my doctorate degree on the 24h.”
Doctor Seul Gi Lee has been recognized in the field of wearable healthcare for her research and has been hired as a researcher in the Holst Centre which is a national research center funded by the Netherlands’ government. She will continue to research on measuring and analyzing biological readings.
2012.04.04 View 9754