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MCM Utilized at Residential Treatment Center in Gyeonggi
The Mobile Clinic Module (MCM) developed by the KAIST Action for Respiratory Epidemics was installed at special residential treatment center in Gyeonggi Province on September 13.
The MCM is an isolate negative pressure unit fitted with high-quality medical equipment, developed by Professor Taek-Jin Nam of the Department of Industrial Design under the KAIST New Deal R&D Initiative. This is also a part of the Korean Disease Control Package Development Project from last July.
In January, a ward with four beds for critical care was installed at the Korea Institute for Radiological & Medical Sciences in Seoul for a trial operation, and two mild cases were treated there. It was also implemented as an isolated negative pressure unit in the Daejeon Konyang University Hospital emergency room in June, and has treated 138 cases since.
The special residential treatment center installed in the Gyeonggi Provincial Academy gymnasium, which consists of 28 beds in 14 rooms (double occupancy) and a multipurpose room (for X-rays and treatment), is to remain open through October 10. Unlike existing treatment centers that have quarantined COVID-19 patients for two weeks, the Gyeonggi MCM will act as a self-treatment-associated short-term treatment center. While in self-treatment, patients showing symptoms requiring special attention will be moved to the MCM, followed by short-term hospitalization of 1-3 days for observation before further measures are taken.
Patients can be treated using the MCM’s own treatment capacities, including in-person and oxygen treatment, X-rays, and IVs. There are individual bathrooms in each room, and the pressure, ventilation, and the automatic opening and closing of the entrance can be centrally monitored and controlled. Patients showing symptoms during treatment will be moved to a specially designated hospital for critical care, and will return to the self-treatment center if no further abnormalities are reported.
The Gyeonggi Provincial Medical Center’s Ansung Hospital will take charge of operating the special treatment center. Each day, one or two doctors, three nurses, two nursing assistants, one administrative staff member, two or three disinfection specialists, and a medical imaging engineer will work in three shifts. There will also be about 20 additional specially designated staff members including KAIST researchers, firefighters, and police officers.
The MCM was internationally recognized as an excellent medical facility not only for its functionality, economic feasibility, and utility, but also for its unique design and aesthetics. It received two Best of Best awards at the Red Dot Award in product design and Communication Design in user interface.
By running this special treatment center, KAIST will conduct research on how to build an optimized model for efficient negative pressure medical units. This research is expected to lead to advances in waste water treatment systems, mobile bathrooms optimized for infectious cases, and MCM user interfaces for electronic devices, etc.
Professor Taek-Jin Nam, the general director of the project and design, said “if there is a gymnasium available, we can convert it into a special treatment center fitted with a waste water treatment system, and pressure equipment in two weeks even without additional infrastructure.”
The head of the KAIST New Deal R&D Initiative Choongsik Bae said, “our MCM research started in July of last year, and in just over a year, it has become a successful and innovative case that has undergone trials and become commercialized in a short period of time.” He added, “In response to COVID-19, KAIST is conducting research and empirical studies, not just in relation to the MCM, but in other areas of disease control as well.”
Based on the excellent disease control technologies developed by KAIST research teams, the KAIST Action for Respiratory Epidemics is conducting technology transfers and industrialization, and is developing a Korean disease control package model
2021.09.15 View 9843 -
How Stingrays Became the Most Efficient Swimmers in Nature
Study shows the hydrodynamic benefits of protruding eyes and mouth in a self-propelled flexible stingray
With their compressed bodies and flexible pectoral fins, stingrays have evolved to become one of nature’s most efficient swimmers. Scientists have long wondered about the role played by their protruding eyes and mouths, which one might expect to be hydrodynamic disadvantages.
Professor Hyung Jin Sung and his colleagues have discovered how such features on simulated stingrays affect a range of forces involved in propulsion, such as pressure and vorticity. Despite what one might expect, their research team found these protruding features actually help streamline the stingrays.
‘The influence of the 3D protruding eyes and mouth on a self-propelled flexible stingray and its underlying hydrodynamic mechanism are not yet fully understood,” said Professor Sung. “In the present study, the hydrodynamic benefit of protruding eyes and mouth was explored for the first time, revealing their hydrodynamic role.”
To illustrate the complex interplay between hydrodynamic forces, the researchers set to work creating a computer model of a self-propelled flexible plate. They clamped the front end of the model and then forced it to mimic the up-and-down harmonic oscillations stingrays use to propel themselves.
To re-create the effect of the eyes and mouth on the surrounding water, the team simulated multiple rigid plates on the model. They compared this model to one without eyes and a mouth using a technique called the penalty immersed boundary method.
“Managing random fish swimming and isolating the desired purpose of the measurements from numerous factors was difficult,” Sung said. “To overcome these limitations, the penalty immersed boundary method was adopted to find the hydrodynamic benefits of the protruding eyes and mouth.”
The team discovered that the eyes and mouth generated a vortex of flow in the forward-backward , which increased negative pressure at the simulated animal’s front, and a side-to-side vortex that increased the pressure difference above and below the stingray. The result was increased thrust and accelerated cruising.
Further analysis showed that the eyes and mouth increased overall propulsion efficiency by more than 20.5% and 10.6%, respectively.
Researchers hope their work, driven by curiosity, further stokes interest in exploring fluid phenomena in nature. They are hoping to find ways to adapt this for next-generation water vehicle designs based more closely on marine animals.
This study was supported by the National Research Foundation of Korea and the State Scholar Fund from the China Scholarship Council.
-ProfileProfessor Hyung Jin SungDepartment of Mechanical EngineeringKAIST
-PublicationHyung Jin Sung, Qian Mao, Ziazhen Zhao, Yingzheng Liu, “Hydrodynamic benefits of protruding eyes and mouth in a self-propelled flexible stingray,” Aug.31, 2021, Physics of Fluids
(https://doi.org/10.1063/5.0061287)
-News release from the American Institute of Physics, Aug.31, 2021
2021.09.06 View 6402 -
Genomic Data Reveals New Insights into Human Embryonic Development
KAIST researchers have used whole-genome sequencing to track the development from a single fertilized-egg to a human body
Genomic scientists at KAIST have revealed new insights into the process of human embryonic development using large-scale, whole-genome sequencing of cells and tissues from adult humans. The study, published in Nature on Aug.25, is the first to analyse somatic mutations in normal tissue across multiple organs within and between humans.
An adult human body comprises trillions of cells of more than 200 types. How a human develops from a single fertilized egg to a fully grown adult is a fundamental question in biomedical science. Due to the ethical challenges of performing studies on human embryos, however, the details of this process remain largely unknown.
To overcome these issues, the research team took a different approach. They analysed genetic mutations in cells taken from adult human post-mortem tissue. Specifically, they identified mutations that occur spontaneously in early developmental cell divisions. These mutations, also called genomic scars, act like unique genetic fingerprints that can be used to trace the embryonic development process.
The study, which looked at 334 single-cell colonies and 379 tissue samples from seven recently deceased human body donors, is the largest single-cell, whole-genome analysis carried out to date. The researchers examined the genomic scars of each individual in order to reconstruct their early embryonic cellular dynamics.
The result revealed several key characteristics of the human embryonic development process. Firstly, mutation rates are higher in the first cell division, but then decrease to approximately one mutation per cell during later cell division. Secondly, early cells contributed unequally to the development of the embryo in all informative donors, for example, at the two-cell stage, one of the cells always left more progeny cells than the other. The ratio of this was different from person to person, implying that the process varies between individuals and is not fully deterministic.
The researchers were also able to deduce the timing of when cells begin to differentiate into individual organ-specific cells. They found that within three days of fertilization, embryonic cells began to be distributed asymmetrically into tissues for the left and right sides of the body, followed by differentiation into three germ layers, and then differentiation into specific tissues and organs.
“It is an impressive scientific achievement that, within 20 years of the completion of human genome project, genomic technology has advanced to the extent that we are now able to accurately identify mutations in a single-cell genome,” said Professor Young Seok Ju from the Graduate School of Medical Science and Engineering at KAIST. “This technology will enable us to track human embryogenesis at even higher resolutions in the future.”
The techniques used in this study could be used to improve our understanding of rare diseases caused by abnormalities in embryonic development, and to design new precision diagnostics and treatments for patients.
The research was completed in collaboration with Kyungpook National University Hospital, the Korea Institute of Science and Technology Information, Catholic University of Korea School of Medicine, Genome Insights Inc, and Immune Square Inc. This work was supported by the Suh Kyungbae Foundation, the Ministry of Health and Welfare of Korea, the National Research Foundastion of Korea.
-PublicationSeongyeol Park, Nanda Mali, Ryul Kim et al. ‘Clonal dynamics in early human embryogenesis inferred from somatic mutation’ Nature Online ahead of print, Aug. 25, 2021 (https://doi.org/10.1038/s41586-021-03786-8)
-ProfileProfessor Young Seok JuLab of Cancer Genomics (https://www.julab.kaist.ac.kr/)Graduate School of Medical Science and EngineeringKAIST
2021.08.31 View 7747 -
A Mechanism Underlying Most Common Cause of Epileptic Seizures Revealed
An interdisciplinary study shows that neurons carrying somatic mutations in MTOR can lead to focal epileptogenesis via non-cell-autonomous hyperexcitability of nearby nonmutated neurons
During fetal development, cells should migrate to the outer edge of the brain to form critical connections for information transfer and regulation in the body. When even a few cells fail to move to the correct location, the neurons become disorganized and this results in focal cortical dysplasia. This condition is the most common cause of seizures that cannot be controlled with medication in children and the second most common cause in adults.
Now, an interdisciplinary team studying neurogenetics, neural networks, and neurophysiology at KAIST has revealed how dysfunctions in even a small percentage of cells can cause disorder across the entire brain. They published their results on June 28 in Annals of Neurology.
The work builds on a previous finding, also by a KAIST scientists, who found that focal cortical dysplasia was caused by mutations in the cells involved in mTOR, a pathway that regulates signaling between neurons in the brain.
“Only 1 to 2% of neurons carrying mutations in the mTOR signaling pathway that regulates cell signaling in the brain have been found to include seizures in animal models of focal cortical dysplasia,” said Professor Jong-Woo Sohn from the Department of Biological Sciences. “The main challenge of this study was to explain how nearby non-mutated neurons are hyperexcitable.”
Initially, the researchers hypothesized that the mutated cells affected the number of excitatory and inhibitory synapses in all neurons, mutated or not. These neural gates can trigger or halt activity, respectively, in other neurons. Seizures are a result of extreme activity, called hyperexcitability. If the mutated cells upend the balance and result in more excitatory cells, the researchers thought, it made sense that the cells would be more susceptible to hyperexcitability and, as a result, seizures.
“Contrary to our expectations, the synaptic input balance was not changed in either the mutated or non-mutated neurons,” said Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering. “We turned our attention to a protein overproduced by mutated neurons.”
The protein is adenosine kinase, which lowers the concentration of adenosine. This naturally occurring compound is an anticonvulsant and works to relax vessels. In mice engineered to have focal cortical dysplasia, the researchers injected adenosine to replace the levels lowered by the protein. It worked and the neurons became less excitable.
“We demonstrated that augmentation of adenosine signaling could attenuate the excitability of non-mutated neurons,” said Professor Se-Bum Paik from the Department of Bio and Brain Engineering.
The effect on the non-mutated neurons was the surprising part, according to Paik. “The seizure-triggering hyperexcitability originated not in the mutation-carrying neurons, but instead in the nearby non-mutated neurons,” he said.
The mutated neurons excreted more adenosine kinase, reducing the adenosine levels in the local environment of all the cells. With less adenosine, the non-mutated neurons became hyperexcitable, leading to seizures.
“While we need further investigate into the relationship between the concentration of adenosine and the increased excitation of nearby neurons, our results support the medical use of drugs to activate adenosine signaling as a possible treatment pathway for focal cortical dysplasia,” Professor Lee said.
The Suh Kyungbae Foundation, the Korea Health Technology Research and Development Project, the Ministry of Health & Welfare, and the National Research Foundation in Korea funded this work.
-Publication:Koh, H.Y., Jang, J., Ju, S.H., Kim, R., Cho, G.-B., Kim, D.S., Sohn, J.-W., Paik, S.-B. and Lee, J.H. (2021), ‘Non–Cell Autonomous Epileptogenesis in Focal Cortical Dysplasia’ Annals of Neurology, 90: 285 299. (https://doi.org/10.1002/ana.26149)
-ProfileProfessor Jeong Ho Lee Translational Neurogenetics Labhttps://tnl.kaist.ac.kr/ Graduate School of Medical Science and Engineering KAIST
Professor Se-Bum Paik Visual System and Neural Network Laboratory http://vs.kaist.ac.kr/ Department of Bio and Brain EngineeringKAIST
Professor Jong-Woo Sohn Laboratory for Neurophysiology, https://sites.google.com/site/sohnlab2014/home Department of Biological SciencesKAIST
Dr. Hyun Yong Koh Translational Neurogenetics LabGraduate School of Medical Science and EngineeringKAIST
Dr. Jaeson Jang Ph.D.Visual System and Neural Network LaboratoryDepartment of Bio and Brain Engineering KAIST
Sang Hyeon Ju M.D.Laboratory for NeurophysiologyDepartment of Biological SciencesKAIST
2021.08.26 View 11284 -
KAIST KPC4IR Presents the AI Global Guide for Healthcare
The benchmark for the responsible usage of AI technology in the healthcare sector will promote clarity and high standards for technological applications
The KAIST Korea Policy Center for the Fourth Industrial Revolution (KPC4IR) published 'Using AI to Support Healthcare Decisions: A Guide for Society.' This global guide is designed to serve as a benchmark for the responsible usage of AI technologies, and will promote clarity and high standards for technological applications in the healthcare sector. The guide details what should be considered when making clinical decisions to help reduce the chances of the AI giving false or misleading results.
The KPC4IR presented the guide in collaboration with the Lloyd’s Register Foundation Institute for the Public Understanding of Risk at the National University of Singapore (NUS IPUR) and Sense about Science, a non-profit organization in the UK specialized in science communication, during the 2021 SIG-KDD (Special Interest Group on Knowledge Discovery and Data Mining) Conference on August 15.
AI technology is being widely used in the healthcare sector and has already proved its accuracy and efficiency in diagnosing and predicting diseases. Despite its huge impact on our daily lives in every sector of society, AI technology has some drawbacks and comes with risks, especially due to biased algorithms.
“We focused on the ‘reliability’ of AI applications in the healthcare sector to make all data well represented, in good quality. The technology will eventually innovate to better serve the people’s new demand, especially critical demands for safety and precision in healthcare services. This global guide will help both developers and people’s understanding of the appropriate technology applications,” says Director So Young Kim at the KPC4IR.
The guide, for instance, says that to scrutinize quality and reliability, the source of the data must be clearly known; the data must have been collected or selected for the purpose it’s being used for; the limitations and assumptions for that purpose have been clearly stated; the biases have been addressed; and it has been properly tested in the real world. It also reflects the importance of the representativeness of data that will affect the accuracy of the AI applications.
“By being transparent and demonstrating the steps taken to check that the AI is reliable, researchers and developers can help give people confidence about providing their data,” the guide states.
For this guide, the KPC4IR and its collaborators collected data after working with numerous experts from the Graduate School of AI at KAIST, the Science and Technology Policy Institute in Korea, Asan Medical Center in Seoul, Seoul National University Bundang Hospital, and AI solution companies.
2021.08.17 View 7107 -
A Study Reveals What Triggers Lung Damage during COVID-19
A longitudinal study of macrophages from SARS-CoV-2 infected lungs offers new insights into dynamic immunological changes
A KAIST immunology research team found that a specific subtype of macrophages that originated from blood monocytes plays a key role in the hyper-inflammatory response in SARS-CoV-2 infected lungs, by performing single-cell RNA sequencing of bronchoalveolar lavage fluid cells. This study provides new insights for understanding dynamic changes in immune responses to COVID-19.
In the early phase of COVID-19, SARS-CoV-2 infected lung tissue and the immediate defense system is activated. This early and fast response is called ‘innate immunity,’ provided by immune cells residing in lungs. Macrophages are major cell types of the innate immune system of the lungs, and newly differentiated macrophages originating from the bloodstream also contribute to early defenses against viruses.
Professor Su-Hyung Park and his collaborators investigated the quantitative and qualitative evaluation of immune responses in the lungs of SARS-CoV-2 infected ferrets. To overcome the limitations of research using patient-originated specimens, the researchers used a ferret infection model to obtain SARS-CoV-2 infected lungs sequentially with a defined time interval.
The researchers analyzed the 10 subtypes of macrophages during the five-day course of SARS-CoV-2 infection, and found that infiltrating macrophages originating from activated monocytes in the blood were key players for viral clearance as well as damaged lung tissue. Moreover, they found that the differentiation process of these inflammatory macrophages resembled the immune responses in the lung tissue of severe COVID-19 patients.
Currently, the research team is conducting a follow-up study to identify the dynamic changes in immune responses during the use of immunosuppressive agents to control hyper-inflammatory response called ‘cytokine storm’ in patients with COVID-19.
Dr. Jeong Seok Lee, the chief medical officer at Genome Insight Inc., explained, “Our analysis will enhance the understanding of the early features of COVID-19 immunity and provide a scientific background for the more precise use of immunosuppressive agents targeting specific macrophage subtypes.”
“This study is the first longitudinal study using sequentially obtained immune cells originating from SARS-CoV-2 infected lungs. The research describes the innate immune response to COVID-19 using single cell transcriptome data and enhances our understanding of the two phases of inflammatory responses,” Professor Park said.
This work was supported by the Ministry of Health and Welfare and KAIST, and was published in Nature Communications on July 28.
-PublicationSu-Hyung Park, Jeong Seok Lee, Su-Hyung Park et al. “Single-cell transcriptome of bronchoalverolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets” Nature Communications (https://doi.org/10.1038/s41467-021-24807-0)
-ProfileProfessor Su-Hyung ParkLaboratory of Translational Immunology and Vaccinologyhttps://ltiv.kaist.ac.kr/
Graduate School of Medical Science and EngineeringKAIST
2021.08.04 View 11473 -
KPC4IR Helping to Create Global Standards for Virtual Transactions
KPC4IR will join the task force for the Global Implementation of Travel Rule Standards
The KAIST Policy Center for the Fourth Industrial Revolution (KPC4IR) will participate in a global initiative to create global standards for virtual asset transactions. As a member of the GI-TRUST (Global Implementation of Travel Rule Standards) task force, the KPC4IR will develop technical standards and relevant policies that support the global implementation of the travel rule for virtual assets in compliance with the recommendations of the Financial Action Task Force’s (FATF).
The FATF is an intergovernmental organization founded in 1989 by the G7 to develop policies to combat money laundering. In June 2019, the FATF extended its Recommendation 16, commonly known as the “travel rule,” to virtual asset services providers (VASPs), requiring both financial institutions and VASPs to aggregate information on the senders and recipients of wire transfers and exchange this information between parties to create a suitable audit trail.
According to the FATF’s recommendation and the G20’s support, jurisdictions, especially G20 member countries, have now applied the travel rule to their respective local laws. Korea also amended the Act on Reporting and Using Specified Financial Transaction Information in March 2020 to include virtual assets in their regulatory scope by March 2022.
The GI-TRUST task force will collaborate with global and local organizations developing travel rule technologies and offer a neutral assessment of proposed solutions. Their activities are aimed at standardizing related authentication protocols and security technologies that help VASPs comply with the travel rule.
The task force will also aid in the pilot testing of travel rule solutions for certain VASPs in Korea. Afterwards, the task force will report on the performance and reliability of the tested travel rule solutions for actual virtual asset transactions, in compliance with the FATF’s guidance.
Besides the KPC4IR, the GI-TRUST task force includes the Global Blockchain Business Council (GBBC), International Digital Asset Exchange Association (IDAXA), and Korea Blockchain Association (KBCA).
Director of the KPC4IR Professor So Young Kim will co-chair the task force. Professor Kim said their approach should be prudential in dealing with the regulations that rely on secure real-name data on top of the opposing governance style of pseudonymization, distribution, and recombination.
She explained, “KAIST has designed the co-evolution of technologies and institutions in conjunction with the global leaders’ groups such as the World Economic Forum and the EC Joint Research Center.”
She expects KAIST’s interdisciplinary, global cooperation to untie the entangled problem between regulations and technologies that obstruct future pathways.
2021.07.30 View 7636 -
Prof. Changho Suh Named the 2021 James L. Massey Awardee
Professor Changho Suh from the School of Electrical Engineering was named the recipient of the 2021 James L.Massey Award. The award recognizes outstanding achievement in research and teaching by young scholars in the information theory community. The award is named in honor of James L. Massey, who was an internationally acclaimed pioneer in digital communications and revered teacher and mentor to communications engineers.
Professor Suh is a recipient of numerous awards, including the 2021 James L. Massey Research & Teaching Award for Young Scholars from the IEEE Information Theory Society, the 2019 AFOSR Grant, the 2019 Google Education Grant, the 2018 IEIE/IEEE Joint Award, the 2015 IEIE Haedong Young Engineer Award, the 2013 IEEE Communications Society Stephen O. Rice Prize, the 2011 David J. Sakrison Memorial Prize (the best dissertation award in UC Berkeley EECS), the 2009 IEEE ISIT Best Student Paper Award, the 2020 LINKGENESIS Best Teacher Award (the campus-wide Grand Prize in Teaching), and the four Departmental Teaching Awards (2013, 2019, 2020, 2021).
Dr. Suh is an IEEE Information Theory Society Distinguished Lecturer, the General Chair of the Inaugural IEEE East Asian School of Information Theory, and a Member of the Young Korean Academy of Science and Technology. He is also an Associate Editor of Machine Learning for the IEEE Transactions on Information Theory, the Editor for the IEEE Information Theory Newsletter, a Column Editor for IEEE BITS the Information Theory Magazine, an Area Chair of NeurIPS 2021, and on the Senior Program Committee of IJCAI 2019–2021.
2021.07.27 View 7070 -
Jungheung to Donate 30B KRW for Semiconductor Research and Education
Jungheung Group, a construction company in Korea, made a pledge to donate 30 billion KRW for semiconductor research and education at KAIST. Junghueng will spend 20 billion KRW to construct the semiconductor education and research facilities that will be established in Pyeongtaek City in collaboration with Samsung Electronics, and 10 billion will go for supporting the educational training program. The pledge ceremony was held at the Daejeon campus with Jungheung Group Chairman Chang-Sun Jung, KAIST President Kwang Hyung Lee, and Pyeongtaek City Mayor Jang-Seon Jung in attendance.
Chairman said, “The only way to earn a competitive edge in this era of technology hegemony is to invest in young talents in the science and technology fields. They will grow up to be excellent experts who will feed tens of thousands of people.” He added, “Donating to nurture future talents is the most rewarding investment we can make for the future.”
President Lee said, “Jungheung’s donation is an investment in the semiconductor industry in Korea, which will be the growth engine for the nation. We will make every effort to foster the world’s best workforce in the semiconductor sector.”
Mayor Jung also expressed high hopes for the advancement of KAIST into ‘Brain City,’ a complex designated with Samsung Electronics for the semiconductor industry.
“The city government will fully support the semiconductor industry and KAIST. In doing so, we look forward to becoming the center of the semiconductor industry in the nation,” announced Mayor Jung.
2021.07.20 View 5119 -
VP Sang Yup Lee Honored with the Pony Chung Innovation Award
Vice President for Research Sang Yup Lee became the recipient of the Innovation Award by the Pony Chung Foundation that was established to honor the late Se-yung Chung, the former chairman of Hyundai Development Company. He will receive 200 million KRW in prize money. Chairman Chung developed Korea’s first domestically manufactured automobile, ‘Pony,’ in the mid-1970s that became the cornerstone of Korea’s auto industry today.
Distinguished Professor Lee, from the Department of Chemical and Biomolecular Engineering, is a pioneering scholar in the field of systems metabolic engineering who developed various micro-organisms for producing a wide range of fuels, chemicals, materials, and natural compounds.
He recently was elected as a foreign member of the Royal Society in the UK and is the first Korean ever elected into the National Academy of Inventors (NAI) in the US as well as one of 13 scholars elected as an International Member of both the National Academy of Sciences (NAS) and the National Academy of Engineering (NAE) in the US.
2021.07.13 View 8537 -
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 11774 -
Study of T Cells from COVID-19 Convalescents Guides Vaccine Strategies
Researchers confirm that most COVID-19 patients in their convalescent stage carry stem cell-like memory T cells for months
A KAIST immunology research team found that most convalescent patients of COVID-19 develop and maintain T cell memory for over 10 months regardless of the severity of their symptoms. In addition, memory T cells proliferate rapidly after encountering their cognate antigen and accomplish their multifunctional roles. This study provides new insights for effective vaccine strategies against COVID-19, considering the self-renewal capacity and multipotency of memory T cells.
COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. When patients recover from COVID-19, SARS-CoV-2-specific adaptive immune memory is developed. The adaptive immune system consists of two principal components: B cells that produce antibodies and T cells that eliminate infected cells. The current results suggest that the protective immune function of memory T cells will be implemented upon re-exposure to SARS-CoV-2.
Recently, the role of memory T cells against SARS-CoV-2 has been gaining attention as neutralizing antibodies wane after recovery. Although memory T cells cannot prevent the infection itself, they play a central role in preventing the severe progression of COVID-19. However, the longevity and functional maintenance of SARS-CoV-2-specific memory T cells remain unknown.
Professor Eui-Cheol Shin and his collaborators investigated the characteristics and functions of stem cell-like memory T cells, which are expected to play a crucial role in long-term immunity. Researchers analyzed the generation of stem cell-like memory T cells and multi-cytokine producing polyfunctional memory T cells, using cutting-edge immunological techniques.
This research is significant in that revealing the long-term immunity of COVID-19 convalescent patients provides an indicator regarding the long-term persistence of T cell immunity, one of the main goals of future vaccine development, as well as evaluating the long-term efficacy of currently available COVID-19 vaccines.
The research team is presently conducting a follow-up study to identify the memory T cell formation and functional characteristics of those who received COVID-19 vaccines, and to understand the immunological effect of COVID-19 vaccines by comparing the characteristics of memory T cells from vaccinated individuals with those of COVID-19 convalescent patients.
PhD candidate Jae Hyung Jung and Dr. Min-Seok Rha, a clinical fellow at Yonsei Severance Hospital, who led the study together explained, “Our analysis will enhance the understanding of COVID-19 immunity and establish an index for COVID-19 vaccine-induced memory T cells.”
“This study is the world’s longest longitudinal study on differentiation and functions of memory T cells among COVID-19 convalescent patients. The research on the temporal dynamics of immune responses has laid the groundwork for building a strategy for next-generation vaccine development,” Professor Shin added. This work was supported by the Samsung Science and Technology Foundation and KAIST, and was published in Nature Communications on June 30.
-Publication:
Jung, J.H., Rha, MS., Sa, M. et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Communications 12, 4043 (2021). https://doi.org/10.1038/s41467-021-24377-1
-Profile:
Professor Eui-Cheol Shin
Laboratory of Immunology & Infectious Diseases (http://liid.kaist.ac.kr/)
Graduate School of Medical Science and Engineering
KAIST
2021.07.05 View 11358