AI-Engineered "Nasal Spray Antiviral Platform" Developed to Block Flu and COVID-19
<(From Left) Professor Hyun Jung Chung, Professor Ho Min Kim, Professor Ji Eun Oh>
<(From Left) Dr. Seungju Yang, Dr. Jeongwon Yun, Ph.D candidate Jae Hyuk Kwon>
Respiratory viruses that have diverse strains and mutate rapidly, such as influenza and COVID-19, are difficult to block perfectly with vaccines alone. To solve this problem, KAIST's research team has successfully developed a nasal (intranasal) antiviral platform using AI technology to overcome the existing limitations of interferon-lambda treatments—namely, being "weak against heat and disappearing quickly from the nasal mucosa."
KAIST announced on December 15th that a joint research team—consisting of Professor Ho Min Ktim and Professor Hyun Jung Chung from the Department of Biological Sciences, and Professor Ji Eun Oh from the Graduate School of Medical Science and Engineering used AI to stably redesign the interferon-lambda protein and combined it with a delivery technology that ensures effective diffusion and long-term retention in the nasal mucosa, thereby implementing a universal prevention technology for various respiratory viruses.
Interferon-lambda is an innate immune protein produced by the body to block viral infections, playing a crucial role in stopping respiratory viruses like the common cold, flu, and COVID-19. However, when formulated as a treatment for nasal administration, its actual efficacy was limited by its vulnerability to heat, degrading enzymes, mucus, and ciliary motion.
The research team used AI protein design technology to precisely reinforce the structural weaknesses of interferon-lambda.
First, they significantly increased stability by changing the loose "loop" structures of the protein—which were prone to instability—into rigid "helix" structures that lock in place like a firm spring.
Additionally, to prevent "aggregation" (proteins sticking together to form lumps), they applied "surface engineering" to make the surface more water-compatible. They also introduced "glycoengineering," adding sugar chain (glycan) structures to the protein surface to make it even more robust and stable.
As a result, the newly produced interferon-lambda showed a massive improvement in stability, surviving for two weeks 50℃ and demonstrated the ability to diffuse rapidly even through thick nasal mucus.
The research team further protected the protein by encapsulating it in microscopic "nanoliposomes" and coated the surface with "low-molecular-weight chitosan." This significantly enhanced "mucoadhesion," allowing the treatment to stick to the nasal lining for an extended period.
When this delivery platform was applied to animal models infected with influenza, a powerful inhibitory effect was confirmed, with the virus level in the nasal cavity decreasing by more than 85%.
This technology is a mucosal immune platform that can block viral infections in their early stages simply by spraying it into the nose. It is expected to be a new therapeutic strategy that can respond quickly not only to seasonal flu but also to unexpected new or mutant viruses.
Professor Ho Min Kim stated, "Through AI-based protein design and mucosal delivery technology, we have simultaneously overcome the stability and retention time limitations of existing interferon-lambda treatments. This platform, which is stable at high temperatures and stays in the mucosa for a long time, is an innovative technology that can be used even in developing countries lacking strict cold-chain infrastructure. It also has great scalability for developing various treatments and vaccines." He added, "This is a meaningful achievement resulting from multidisciplinary convergence research, covering everything from AI protein design to drug delivery optimization and immune evaluation through infection models."
This research involved Dr. Jeongwon Yun from the KAIST InnoCORE (AI-Co-Research & Eudcation for innovative Drug Institute, AI-CRED Institute) Dr. Seungju Yang from the Department of Biological Sciences, and PhD student Jae Hyuk Kwon from the Graduate School of Medical Science and Engineering as co-first authors. The results were published consecutively in the renowned international journals Advanced Science (Nov 20) and Biomaterials Research (Nov 21).
Paper 1: Computational Design and Glycoengineering of Interferon-Lambda for Nasal Prophylaxis against Respiratory Viruses, Advanced Science, DOI: 10.1002/advs.202506764
Paper 2: Intranasal Nanoliposomes Delivering Interferon Lambda with Enhanced Mucosal Retention as an Antiviral, Biomaterials Research, DOI: 10.34133/bmr.0287
This research was conducted with support from the KAIST InnoCORE Program, Mid-Career Researcher Support Program and the Bio-Medical Technology Development Program through the National Research Foundation of Korea (NRF), Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the KAIST Convergence Research Institute Operation Program, and the Institute for Basic Science (IBS).
Electrosprayed Micro Droplets Help Kill Bacteria and Viruses
With COVID-19 raging around the globe, researchers are doubling down on methods for developing diverse antimicrobial technologies that could be effective in killing a virus, but harmless to humans and the environment.
A recent study by a KAIST research team will be one of the responses to such efforts. Professor Seung Seob Lee and Dr. Ji-hun Jeong from the Department of Mechanical Engineering developed a harmless air sterilization prototype featuring electrosprayed water from a polymer micro-nozzle array. This study is one of the projects being supported by the KAIST New Deal R&D Initiative in response to COVID-19. Their study was reported in Polymer.
The electrosprayed microdroplets encapsulate reactive oxygen species such as hydroxyl radicals, superoxides that are known to have an antimicrobial function. The encapsulation prolongs the life of reactive oxygen species, which enable the droplets to perform their antimicrobial function effectively. Prior research has already proven the antimicrobial and encapsulation effects of electrosprayed droplets.
Despite its potential for antimicrobial applications, electrosprayed water generally operates under an electrical discharge condition, which can generate ozone. The inhalation of ozone is known to cause damage to the respiratory system of humans. Another technical barrier for electrospraying is the low flow rate problem. Since electrospraying exhibits the dependence of droplet size on the flow rate, there is a limit for the amount of water microdroplets a single nozzle can produce.
With this in mind, the research team developed a dielectric polymer micro-nozzle array to perform the multiplexed electrospraying of water without electrical discharge. The polymer micro-nozzle array was fabricated using the MEMS (Micro Electro-Mechanical System) process. According to the research team, the nozzle can carry five to 19 micro-nozzles depending on the required application.
The high aspect ratio of the micro-nozzle and an in-plane extractor were proposed to concentrate the electric field at the tip of the micro-nozzle, which prevents the electrical discharge caused by the high surface tension of water. A micro-pillar array with a hydrophobic coating around the micro-nozzle was also proposed to prevent the wetting of the micro-nozzle array.
The polymer micro-nozzle array performed in steady cone jet mode without electrical discharge as confirmed by high-speed imaging and nanosecond pulsed imaging. The water microdroplets were measured to be in the range of six to 10 μm and displayed an antimicrobial effect on Escherichia coli and Staphylococcus aureus.
Professor Lee said, “We believe that this research can be applied to air conditioning products in areas that require antimicrobial and humidifying functions.”
Publication:
Jeong, J. H., et al. (2020) Polymer micro-atomizer for water electrospray in the cone jet mode. Polymer. Vol. No. 194, 122405. Available online at https://doi.org/10.1016/j.polymer.2020.122405
Profile: Seung Seob Lee, Ph.D.
sslee97@kaist.ac.kr
http://mmst.kaist.ac.kr/
Professor
Department of Mechanical Engineering (ME)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Ji-hun Jeong, Ph.D.
jiuni6022@kaist.ac.kr
Postdoctoral researcher
Department of Mechanical Engineering (ME)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
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Material-Independent Nanocoating Antimicrobial Spray Significantly Extends the Shelf Life of Produce
The edible coating on produce has drawn a great deal of attention in the food and agricultural industry. It could not only prolong postharvest shelf life of produce against external changes in the environment but also provide additional nutrients to be useful for human health. However, most versions of the coating have had intrinsic limitations in their practical application. First, highly specific interactions between coating materials and target surfaces are required for a stable and durable coating. Even further, the coating of bulk substrates, such as fruits, is time consuming or is not achievable in the conventional solution-based coating. In this respect, material-independent and rapid coating strategies are highly demanded.
The research team led by Professor Insung Choi of the Department of Chemistry developed a sprayable nanocoating technique using plant-derived polyphenol that can be applied to any surface. This new nanocoating process can be completed in seconds to form nanometer-thick films, allowing for the coating of commodity goods, such as shoe insoles and fruits, in a controlled fashion. For example, spray-coated mandarin oranges and strawberries show significantly-prolonged postharvest shelf life, suggesting the practical potential in edible coatings of perishable produce.
The technology has been patented and is currently being commercialized for widespread use as a means of preserving produce. The research results have recently been published in Scientific Reports on Aug 1.
Polyphenols, a metabolite of photosynthesis, possess several hydroxyl groups and are found in a large number of plants showing excellent antioxidant properties. They have been widely used as a nontoxic food additive and are known to exhibit antibacterial, as well as potential anti-carcinogenic capabilities. Polyphenols can also be used with iron ions, which are naturally found in the body, to form an adhesive complex, which has been used in leather tanning, ink, etc.
The research team combined these chemical properties of polyphenol-iron complexes with spray techniques to develop their nanocoating technology. Compared to conventional immersion coating methods, which dip substrates in specialized coating solutions, this spray technique can coat the select areas more quickly. The spray also prevents cross contamination, which is a big concern for immersion methods. The research team has showcased the spray’s ability to coat a variety of different materials, including metals, plastics, glass, as well as textile fabrics. The polyphenol complex has been used to form antifogging films on corrective lenses, as well as antifungal treatments for shoe soles, demonstrating the versatility of their technique.
Furthermore, the spray has been used to coat produce with a naturally antibacterial, edible film. The coatings significantly improved the shelf life of tangerines and strawberries, preserving freshness beyond 28 days and 58 hours, respectively. (Uncoated fruit decomposed and became moldy under the same conditions). See the image below.
a –I, II: Uncoated and coated tangerines incubated for 14 and 28 days in daily-life settings
b –I: Uncoated and coated strawberries incubated for 58 hours in daily-life settings
b –II: Statistical investigation of the resulting edibility.
Professor Choi said, “Nanocoating technologies are still in their infancy, but they have untapped potential for exciting applications. As we have shown, nanocoatings can be easily adapted for several different uses, and the creative combination of existing nanomaterials and coating methods can synergize to unlock this potential.”
Professor Bae Sang Min Wins Multiple Prestigious Design Awards
Summer is perfect for many outdoor activities, but it is also the season for mosquitoes, an annoying pest that makes outdoor experiences unpleasant and sometimes even dangerous. An easy-to-use and environmentally-friendly spray, “Sound Spray” (http://idsa.org/soundspray-self-generating-non-toxic-ultrasonic-anti-mosquito-spray), which repels mosquitoes by setting off ultrasonic waves, has been developed by a research team at KAIST. The spray produces sounds similar to those of mosquitoes’ natural predators.
Sound Spray made the list of finalists in the category of "Social Impact Design" from the 2012 International Design Excellence Awards (IDEA). The IDEA is one of the most renowned design competitions in the world, which has been held annually by the Industrial Designers Society of America (IDSA).
Inside Sound Spray is a battery that generates electricity when a user shakes the spray bottle. Electrical energy produced by the battery creates an ultrasonic sound that mosquitoes dislike, thereby discouraging their contact with human skin. Professor Sangmin Bae from the Department of Industrial Design at KAIST explains,
“In regions such as Africa or Southeast Asia, mosquitoes are still posing a big threat to public health. Unlike Freon-based, disposable insect repellents on the market, Sound Spray is eco-friendly, easy to carry around, reusable, and affordable. I plan to commercialize and distribute it to nations in Africa or Southeast Asia to help them combat against malaria, an infectious disease that patients contract through mosquito bites.”
Professor Bae also received another award from the 2012 IDEA in the area of Commercial and Industrial Products: a bronze medal for a milling machine, the Namsun Milling Machine (http://www.idsa.org/namsunnew-innovative-milling-machine-design). The machine has large windows on each side of its main body that display a transparent workflow so that users easily understand the machine’s operation status. Curved lines are actively used for the exterior design of the machine to create a more friendly work environment.
In addition to the 2012 IDEA, Professor Bae has participated in other major international design awards, including the Red Dot Award, the If Design Award Japan, and the Good Design Award, from which his research team has received a total of 41 prizes.
Professor Bae initiated a campaign in 2005 called “Philanthropy Design,” through which he has donated many of his designs to help people in need. For more on his research, please visit http://www.coroflot.com/frame29/Portfolio1.