AniFaceDrawing: Delivering generative AI-powered high-quality anime portraits for beginners

Researchers use a generative artificial intelligence framework to create high-quality anime portraits from incomplete freehand sketches to remove creative barriers for general users

Reports and Proceedings

JAPAN ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

 

IMAGE: IMAGE GENERATIVE AI FACES INHERENT DIFFICULTIES IN GENERATING IMAGES FROM INCOMPLETE LINE DRAWING WITH SMALL AREAS MISSING AND SOMETIMES EVEN FROM COMPLETE SKETCHES. THE PROPOSED ANIFACEDRAWING SYSTEM CAN GENERATE HIGH-QUALITY RESULTS THAT CONSISTENTLY MATCH THE INPUT SKETCH THROUGHOUT THE SKETCHING PROCESS. THE IMAGE DEPICTS (A) THE FINAL USER SKETCHES, (B) THE GUIDANCE IN DETAIL MODE (COLOR LINES REPRESENT THE SEMANTIC SEGMENTED PARTS), AND (C) THE GENERATED COLOR DRAWINGS FROM (A) AFTER THE FINAL REFERENCE IMAGE SELECTION. view more 

CREDIT: HAORAN XIE FROM JAIST.

Ishikawa, Japan -- Anime, the Japanese art of animation, comprises hand-drawn sketches in an abstract form with unique characteristics and exaggerations of real-life subjects. While generative artificial intelligence (AI) has found use in the content creation such as anime portraits, its use to augment human creativity, and guide freehand drawings proves challenging. The primary challenge lies with the generation of suitable reference images corresponding with the incomplete and abstract strokes made during the freehand drawing process. This is particularly true when the strokes created during the drawing process are incomplete and offer insufficient information for generative AI to predict the final shape of the drawing.

To tackle this problem, a research team from Japan Advanced Institute of Science and Technology (JAIST) and Waseda University in Japan, sought to develop a novel generative AI tool that offers progressive drawing assistance and helps generate anime portraits from freehand sketches. The tool is based on a sketch-to-image (S2I) deep learning framework that matches raw sketches with latent vectors of the generative model. It employs a two-stage training strategy through the pre-trained Style Generative Adversarial Network (StyleGAN)—a state-of-the-art generative model that uses adversarial networks to generate new images.

The team, led by Dr. Zhengyu Huang from JAIST, including Associate Professor Haoran Xie and Professor Kazunori Miyata, and Lecturer Tsukasa Fukusato from Waseda University proposed a novel "stroke-level disentanglement”, a strategy that associates input strokes of a freehand sketch with edge-related attributes, in the latent structural code of StyleGAN. This approach allows users to manipulate the attribute parameters, thereby having greater autonomy over the properties of generated images. Dr. Huang says, “We introduced an unsupervised training strategy for stroke-level disentanglement in StyleGAN, which enables the automatic matching of rough sketches with sparse strokes to the corresponding local parts in anime portraits, all without the need for semantic labels.”

This study will be presented at ACM SIGGRAPH 2023, the premier conference for computer graphics and interactive techniques and the only CORE ranking A* conference in the research fields worldwide.

Regarding the development of the tool, Prof. Xie adds, “We first trained an image encoder using a pre-trained StyleGAN model as a teacher encoder. In the second stage, we simulated the drawing process of generated images without additional data to train the sketch encoder for incomplete progressive sketches. This helped us generate high-quality portrait images that align with the disentangled representations of teacher encoder.”

To further highlight the effectiveness and usability of AniFaceDrawing in aiding users with anime portrait creation, the team conducted a user study. They invited 15 graduate students to draw digital freehand anime-style portraits using the AniFaceDrawing tool, with the option to switch between rough and detailed guidance modes for line art. While the former provided prompts for specific facial parts, the latter provided prompts for the full-face portrait based on the user’s drawing progress. Participants could pin the generated guidance once it matched their expectations, and further refine their input sketch. This tool also allowed participants to select a reference image to generate a color portrait of their input sketch. Next, they evaluated the tool for user satisfaction and guidance matching through a survey.

The team noted that the system consistently provided high-quality facial guidance and effectively supported the creation of anime-style portraits, by not only enhancing user sketches, but also by generating desirable corresponding colored images. Prof. Fukusato remarks, “Our system could successfully transform the user’s rough sketches into high-quality anime portraits. The user study indicated that even novices could make reasonable sketches with the help of the system and end up with high-quality color art drawings”. 

“Our generative AI framework enables users, regardless of their skill level and experience, to create professional anime portraits even from incomplete drawings. Our approach consistently produces high-quality image generation results throughout the creation process, regardless of the drawing order or how poor the initial sketches are,” summarizes Prof. Miyata.

In the long run, these findings can help democratize AI technology and assist users with creative tasks, thereby augmenting their creative capacity without technological barriers.

###

 

Reference

Title of original paper:	AniFaceDrawing: Anime Portrait Exploration during Your Sketching
Authors:	Zhengyu Huang, Haoran Xie, Tsukasa Fukusato, Kazunori Miyata
Conference:	ACM SIGGRAPH 2023
Project:	http://www.jaist.ac.jp/~xie/AniFaceDrawing.html
Video:	https://youtu.be/GcL67h8QEOY
DOI:	https://doi.org/10.1145/3588432.3591548

                                   

About Japan Advanced Institute of Science and Technology, Japan

Founded in 1990 in Ishikawa prefecture, the Japan Advanced Institute of Science and Technology (JAIST) was the first independent national graduate school in Japan. After 30 years of steady progress, JAIST has become one of Japan’s top-ranking universities. JAIST counts with multiple satellite campuses and strives to foster capable leaders with a state-of-the-art education system where diversity is key; about 40% of its alumni are international students. The university has a unique style of graduate education based on a carefully designed coursework-oriented curriculum to ensure that its students have a solid foundation to conduct cutting-edge research. JAIST also works closely both with local and overseas communities by promoting industry–academia collaborative research.

 

About Associate Professor Haoran Xie from Japan Advanced Institute of Science and Technology, Japan

Dr. Haoran Xie is an Associate Professor at the Japan Advanced Institute of Science and Technology (JAIST), Japan. With a research career spanning over a decade, Dr. Xie has over 100 publications to his credit and holds a Ph.D. in Computer Graphics from JAIST. His research interests focus on User Interfaces for Augmented Intelligence—especially for content creation, machine learning, human augmentation, and other artificial intelligence (AI)-related applications. Prof. Xie’s work has garnered him many academic awards, including several Best Paper Awards in international conferences, and FUNAI Research Award for Young Scientists. His work has been reported by various medias include Tech Xplore, China Science Daily, Nikkan Kogyo Shimbun and ITmedia NEWS.

 

Funding information

This research was supported by the JAIST Research Fund, Kayamori Foundation of Informational Science Advancement, JSPS KAKENHI JP20K19845, and JP19K20316.

---

DOI

10.1145/3588432.3591548 

ARTICLE TITLE

AniFaceDrawing: Anime Portrait Exploration during Your Sketching

 

NUS scientists develop a new class of artificial water channels for more efficient industrial water purification

These self-assembling, precise and complex nanostructures can help to purify water more efficiently

Peer-Reviewed Publication

NATIONAL UNIVERSITY OF SINGAPORE

 

IMAGE: A TEAM OF SCIENTISTS FROM THE NATIONAL UNIVERSITY OF SINGAPORE COMPRISING (LEFT TO RIGHT) PROFESSOR PRAKASH KUMAR, PROFESSOR MANJUNATHA KINI, DR LI JIANWEI AND DR PANNAGA KRISHNAMURTHY, HAS DEVELOPED A NEW CLASS OF ARTIFICIAL WATER CHANNELS FOR MORE EFFICIENT INDUSTRIAL WATER PURIFICATION. view more 

CREDIT: NATIONAL UNIVERSITY OF SINGAPORE

Singapore, 02 Aug 2023 -- A team led by scientists from the National University of Singapore's (NUS) Department of Biological Sciences in collaboration with the French Centre for Scientific Research (CNRS) has successfully synthesised a special protein-mimic that can self-assemble into a pore structure. When incorporated into a lipid membrane, the pores permit selective transport of water across the membrane while rejecting salt (ions). These protein-mimics, known as ‘oligourea foldamers’, represent an entirely new class of artificial water channels (AWC) that can be used to improve the energy-efficiency of current methods of industrial water purification.

Current methods of water purification involve the use of reverse osmosis and membrane distillation technologies. Reverse osmosis, however, is a highly energy-intensive process as high pressures are needed to pass seawater or wastewater through a series of semi-permeable membranes to remove salts and other pollutants. In light of climate change and the growing demand for fresh water, there is an impetus to develop more energy-efficient, water-selective membranes for large-scale desalination purposes. This invention represents an excellent contribution to these efforts. The relatively high water permeability of the pores formed by these oligourea foldamers suggests that overall energy requirement for water purification can potentially be reduced.

Addressing the limitations of conventional membrane technologies

Research in this field has largely focused on fabricating membranes with aquaporins, which are naturally-occurring proteins containing pores that allow water molecules to pass through in a single file. They are known as ‘water channels’ and can be found in the cell membranes of all living cells including microbes, plant and animal cells. Due to the complex structure of aquaporin, synthesising sufficient quantities of this bulky protein for use in water purification membranes remains an expensive and time-consuming process.

In a paper published in the scientific journal Chem on 8 May 2023, a team of NUS scientists led by Professor Prakash Kumar described a breakthrough in the development of a simpler molecular component that can self-assemble to generate transmembrane channel-like structures with a pore. These structures mimic the functions of aquaporin, allowing only water molecules to cross the membrane while salts and other pollutants are rejected. The individual oligourea foldamers are also much smaller in size at just 10 amino acid-residues long – which makes them easier to modify, synthesise, and purify compared to aquaporin or other classes of AWC.

How it works

The foldamers are amphiphilic in nature, which means that they possess different charges which allow them to assemble into more complex structures, similar to how magnets tend to clump together in a ball when they are in close proximity with each other. The resulting complex, or quaternary, structures contain pore-like water channels which are further stabilised by strong bonds known as hydrophobic and electrostatic interactions.

The hydrophobic components are clustered on the exterior that allows insertion into lipid membranes. The interior (lumen) of the pore is more hydrophilic, which allows water molecules to move across the membrane while rejecting ions from passing through. And this is responsible for the selective water permeability across lipid membranes observed in lab tests. The scientists discovered that the oligourea foldamers were similar in function to natural porin-like structures, which makes them viable potential candidates for the fabrication of AWC membranes for water purification.

Greater stability and resistance to degradation

The foldamers developed by the NUS researchers were also demonstrated to be more robust compared to other AWCs.

Normal proteins are made up of amino acids joined together by peptide bonds. These peptide bonds are vulnerable to be cut by microbial enzymes that digest proteins, and such microbes exist in unprocessed water. In their research, NUS scientists replaced the peptide bonds with urea bonds, which makes the oligourea foldamers less susceptible to enzymatic and microbial degradation.

First-of-its-kind protein-mimics that self-assemble into pores

The development of the oligourea foldamers marks the first published attempt to create AWCs using short molecular chains that can self-assemble into precise nanostructures with high porosity and selectivity for water molecules.

Prof Kumar, who has a joint appointment with the NUS Environment Research Institute, said, “The discovery of this new class of artificial water channels is significant because the individual foldamer molecules do not contain any pores, unlike other AWCs where the pores are found within their larger molecular structure. In our novel design, the water-selective pores only emerge when the individual units self-assemble. The high-water permeability coupled with resistance to proteolytic degradation makes these foldamers excellent candidates for industrial water purification applications.”

Next steps

In the initial phase, the team of scientists applied the foldamers to a test membrane to demonstrate the water purification capabilities of the self-assembling molecules. For the next phase of research, the team plans to optimise the production of the foldamers and apply them to a larger membrane, before trialling its efficiency in an industrial water purification facility.  

---

JOURNAL

Chem

DOI

10.1016/j.chempr.2023.04.007 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Nature-inspired synthetic oligourea foldamer channels allow water transport with high salt rejection

 

Solar-driven conversion of waste plastics into their building blocks

Peer-Reviewed Publication

DALIAN INSTITUTE OF CHEMICAL PHYSICS, CHINESE ACADEMY SCIENCES

 

IMAGE: INSPIRED BY THE WARMING EARTH’S GREENHOUSE EFFECT, WE DESIGN A CATALYST ARCHITECTURE THAT ENABLES WAVES SELECTIVELY TO PASS THROUGH. THIS GREENHOUSE MIMIC IS COMPOSED OF A CARBONIZED MOF CORE WITH A MESOPOROUS SILICA SHEATH. WHEN BATHED IN SUNLIGHT, THE BLACK CORE GENERATES HEAT, WHICH IS TRAPPED THEREIN BY THE INFRARED SHIELDING EFFECTS OF THE MESOPORES, THUS BOOSTING THE RECYCLING EFFICIENCY OF WASTE PLASTICS. view more 

CREDIT: CHINESE JOURNAL OF CATALYSIS

Photothermal catalysis, fueled by clean solar energy, offers an efficient solution for converting waste plastic into valuable chemicals. This catalytic process harnesses the power of solar energy and converts it into chemical energy. However, the development of photothermal catalysts that exhibit high conversion efficiency and catalytic activity poses significant challenges.

A recent breakthrough comes from a research team led by Prof. Jinxing Chen from Soochow University, China. They have successfully developed an integrated photothermal catalyst comprising c-ZIF-8 coated with a SiO2 layer. This innovative approach focuses on enhancing catalytic activity by minimizing thermal radiation loss and maximizing the localized heating effect of the catalyst. The results were published in Chinese Journal of Catalysis (https://doi.org/10.1016/S1872-2067(23)64435-3).

This study introduces a novel catalyst design approach that involves the synthesis of ZIF-8 nanoparticles using a template method. To create an integrated photothermal catalyst (c-ZIF-8@SiO2), a layer of SiO2 is coated onto the surface of ZIF-8, followed by a high-temperature carbonization treatment. The internal carbon material within the catalyst absorbs solar energy and generates heat, while the outer SiO2 layer selectively allows penetration of solar light, which is then absorbed by the carbon core. This design effectively reduces thermal radiation loss from the internal carbon core and enhances the local thermal effect during the photothermal catalysis process. Furthermore, the SiO2 shell provides a protective effect, resulting in the catalyst's high stability. Overall, this catalyst design strategy offers a universal method for enhancing the local thermal effect in photothermal catalysis and holds potential applications in the development of efficient photothermal catalytic systems.

By irradiating sunlight, the c-ZIF-8@25SiO2 catalyst can efficiently upcycle PET into valuable monomers. The PET glycolysis experiment under outdoor sunlight and the selective recovery of PET from mixed plastics further demonstrate the promising applications in photothermal catalytic PET glycolysis. Photothermal catalysis not only contributes to energy conservation and emission reduction, promoting green and sustainable development but also provides new ideas and methods for efficient chemical recycling of plastics.

###

About the Journal

Chinese Journal of Catalysis is co-sponsored by Dalian Institute of Chemical Physics, Chinese Academy of Sciences and Chinese Chemical Society, and it is currently published by Elsevier group. This monthly journal publishes in English timely contributions of original and rigorously reviewed manuscripts covering all areas of catalysis. The journal publishes Reviews, Accounts, Communications, Articles, Highlights, Perspectives, and Viewpoints of highly scientific values that help understanding and defining of new concepts in both fundamental issues and practical applications of catalysis. Chinese Journal of Catalysis ranks at the top one journal in Applied Chemistry with a current SCI impact factor of 16.5. The Editors-in-Chief are Profs. Can Li and Tao Zhang.

At Elsevier http://www.journals.elsevier.com/chinese-journal-of-catalysis

Manuscript submission https://mc03.manuscriptcentral.com/cjcatal

---

JOURNAL

Chinese Journal of Catalysis

 

The 2022 Sichuan-Chongqing spatio-temporally compound extremes: a bitter taste of novel hazards

Peer-Reviewed Publication

SCIENCE CHINA PRESS

This study is led by Dr. Zengchao Hao (College of Water Sciences, Beijing Normal University) and Dr. Yang Chen (Chinese Academy of Meteorological Sciences). This article documents the unfolding process, reason and impact of compounding and cascading amongst multiple weather and climate extremes during the course of 2022 summer, across the Sichuan Chongqing region.

An exceptionally severe and sustained hot—drought in afflicting the Sichuan Chongqing region increased the dryness of forests, creating flammable conditions and sparking the widespread wildfires near Chongqing. Subsequent extreme precipitation, as a part of southwest China autumn rainfall, coincidently fell on the overheated and burned grounds, and elevated the risk of geological hazards such as flash floods and mudslides as a result. The rapid sequence of these weather and climate extremes led to impacts cascading and multiplying across sectors, for instance human health, energy, agriculture, industry and emergency response. Both natural weather and climate variability and man-made climate change are at play in shaping the compound event. The team also pointed out underestimated socioeconomic and ecological vulnerability and therefore lack of preparedness to increasingly connected extremes.

Finally, the team proposed several key steps for addressing the imminent threat of compound and cascading hazards, including understanding and predicting extremes from a multivariate perspective, improving impact quantification and risk assessment through the compound event lens, and devising adaptation planning tailored to compound and cascading events.

See the article:

The 2022 Sichuan-Chongqing spatio-temporally compound extremes: a bitter taste of novel hazards

https://doi.org/10.1016/j.scib.2023.05.034

---

JOURNAL

Science Bulletin

DOI

10.1016/j.scib.2023.05.034 

 

Researchers discover the reason behind tans appearing only after we’ve left the beach

A scientific mystery solved

Peer-Reviewed Publication

TEL-AVIV UNIVERSITY

 

IMAGE: PROF. CARMIT LEVY view more 

CREDIT: TEL AVIV UNIVERSITY

Beachgoers are familiar with the experience of spending hours in the sun, going home, and noticing only hours later that their skin has changed color. A new Tel Aviv University study uncovers the science behind the mystery of why the body's tanning process does not occur immediately after sun exposure, but only after a few hours or even days. The research findings reveal the mechanism behind this phenomenon, according to which the body’s initial response is to prioritize repairing DNA damage in the skin cells, which inhibits the mechanism responsible for skin pigmentation, commonly known as tanning.

 

The study, published in the Nature Group’s Journal of Investigative Dermatology, was led by doctoral student Nadav Elkoshi and Prof. Carmit Levy of the Department of Human Molecular Genetics and Biochemistry at Tel Aviv University’s Faculty of Medicine, and in collaboration with a number of other researchers from Tel Aviv University, Wolfson Medical Center, the Weizmann Institute of Science, the University of California, and Paris-Saclay University.

 

Nadav Elkoshi explains: “We have two mechanisms designed to protect the skin from exposure to dangerous UV radiation. The first mechanism repairs the DNA in the skin cells damaged by the radiation, while the second mechanism involves increased production of melanin, which darkens the skin in order to protect it from future exposure to radiation. In our study, we discovered why the tanning phenomenon does not occur immediately when the body is exposed to the sun, but only following a delay. It turns out that the mechanism that repairs our DNA takes precedence over all other systems in the cell, temporarily inhibiting the pigmentation mechanism. Only after the cells repair the genetic information to the best of their ability do they begin to produce the increased melanin.”

 

To test their hypothesis, the Tel Aviv University researchers activated the DNA repair mechanism in both animal models and human skin tissues. In both, a tan developed even without any exposure to UV radiation, substantiating their findings.

 

Prof. Carmit Levy: “The genetic information must be protected from mutations, so this repair mechanism takes precedence inside the cell during exposure to ultraviolet radiation from the sun. The DNA repair mechanism essentially tells all the other mechanisms in the cell, ‘Stop everything, and let me work in peace.’ One system effectively paralyzes the other, until the DNA correction reaches its peak, which occurs a few hours after the UV exposure. Only then does the pigment production mechanism get to work. In our previous research, we showed that a protein called MITF, which is activated during exposure, is responsible for regulating these two mechanisms. In the current study we show that another protein, called ATM, which plays a key role in DNA repair, activates one mechanism while disabling the other. This process likely harnesses the pigmentation mechanism’s components to maximize the chances of the cell surviving without mutations following radiation exposure.”

 

Prof. Levy concludes: “This scientific discovery has revealed a molecular mechanism that could serve as a foundation for further research that may lead to innovative treatments that will provide maximum protection of the skin against radiation damage; in the long run, it may even contribute to the prevention of skin cancer.”

 

Link to the article:

https://www.sciencedirect.com/science/article/pii/S0022202X23021243

---

DOI

10.1016/j.jid.2023.03.1686 

Secondary school students have difficulty identifying bird species

According to a study by the University of the Basque Country (UPV/EHU), their knowledge of biosphere reserves, marshes and bird migration is limited

Peer-Reviewed Publication

UNIVERSITY OF THE BASQUE COUNTRY

 

IMAGE: THE STUDY CONCLUDES THAT ONE-DAY PROGRAMMES DO NOT AFFECT ENVIRONMENTAL EDUCATION; WHILE THEY SERVE TO PROMOTE ENVIRONMENTAL KNOWLEDGE AND ATTITUDES IN THE SHORT TERM, THEIR EFFECTIVENESS IS LIMITED view more 

CREDIT: TERE ORMAZABAL. UPV/EHU

In Western societies, the way nature and the environment are understood is very important, as knowledge of them can influence environmental attitudes. Environmental education is a key tool when it comes to increasing awareness, and a range of programmes are offered in both formal and informal settings.  The Urdaibai Bird Center (UBC), located in the heart of the Urdaibai Biosphere Reserve, has numerous habitats necessary for the observation and conservation of migratory birds and is also an ideal location for running environmental education programmes.

Although programmes to bring biodiversity closer to young people have been run for many years in these settings, their effectiveness has not been evaluated until now. Based on environmental education programmes of this type, researchers from the UPV/EHU's Department of Didactics of Mathematics, Experimental and Social Sciences analysed the extent to which 908 secondary school students taking part in the Urdaibai Bird Center's activities for a day assimilated what they had seen and learnt.

To do this, the students completed a written questionnaire to ascertain their perceptions about the Urdaibai Biosphere Reserve and the marshes, their interest in biodiversity, their ability to identify bird species, their knowledge of bird migration, and their attitude towards conservation.

The researcher Unai Ortega emphasised that the main aim of the research was, firstly, to diagnose the students’ knowledge and attitudes and, secondly, to evaluate these environmental education programmes. “They are very common, but their effectiveness has not been evaluated, so we need to know how well these programmes are achieving their objectives,” he explained.

 

The importance of environmental literacy 

The researchers found that secondary school students have scant knowledge of biosphere reserves, marshes and bird migration, especially when it comes to identifying bird species. However, despite the high scores in environmental attitudes, many students are of the opinion that conservation efforts in these environments are excessive and hinder economic development. The results also showed that students from rural areas and those living in or around the Urdaibai Biosphere Reserve know more about local biodiversity, and so do students who in primary school drew up a plan related to birds.

The study concludes that “one-day programmes do not affect environmental education”, said Ortega. “While useful in promoting environmental knowledge and attitudes in the short term, these programmes are of limited effectiveness.” So the researchers pointed out that it might be advisable to adapt the environmental education programme of the Urdaibai Bird Center so that it could be included in formal contexts through practical activities or projects, and so that the results could be systematically evaluated. They stressed the importance of continuing to develop “long-term strategies” for systematic evaluations of this type.

Ortega highlighted the importance of emotional attachment in environmental literacy. In his opinion, it is “essential to feel that it is worthwhile caring for what needs to be cared for”. In this respect, many of us “have participated in this type of programme, but the level of environmental literacy has not increased; on the contrary, the data show that this literacy is on the decline”, he pointed out.

 

Additional information 

This study was supported by a Basque Government grant awarded to the IKASGARAIA research group.
Unai Ortega is a lecturer in the Primary Education and Social Education undergraduate degree courses at the UPV/EHU.

---

JOURNAL

International Journal of Environmental Research and Public Health

DOI

10.3390/ijerph20105769 

ARTICLE TITLE

Secondary Students’ Knowledge on Birds and Attitudes towards Conservation: Evaluation of an Environmental Education Program

 

Novel molecules fight viruses by bursting their bubble-like membranes

Targeting the membrane of a virus, rather than its proteins, could lead to a new generation of antivirals

Peer-Reviewed Publication

NEW YORK UNIVERSITY

 

VIDEO: PEPTOIDS INACTIVATE ENVELOPED VIRUSES BY DISRUPTING THEIR MEMBRANES. view more 

CREDIT: DAVID SONG/NYU

Antiviral therapies are notoriously difficult to develop, as viruses can quickly mutate to become resistant to drugs. But what if a new generation of antivirals ignores the fast-mutating proteins on the surface of viruses and instead disrupts their protective layers?

 

“We found an Achilles heel of many viruses: their bubble-like membranes. Exploiting this vulnerability and disrupting the membrane is a promising mechanism of action for developing new antivirals,” said Kent Kirshenbaum, professor of chemistry at NYU and the study’s senior author.

 

In a new study published Aug. 2 in the journal ACS Infectious Diseases, the researchers show how a group of novel molecules inspired by our own immune system inactivates several viruses, including Zika and chikungunya. Their approach may not only lead to drugs that can be used against many viruses, but could also help overcome antiviral resistance.

 

The urgent need for new antivirals

Viruses have different proteins on their surfaces that are often the targets of therapeutics like monoclonal antibodies and vaccines. But targeting these proteins has limitations, as viruses can quickly evolve, changing the properties of the proteins and making treatments less effective. These limitations were on display when new SARS-CoV-2 variants emerged that evaded both the drugs and the vaccines developed against the original virus.

 

“There is an urgent need for antiviral agents that act in new ways to inactivate viruses,” said Kirshenbaum. “Ideally, new antivirals won’t be specific to one virus or protein, so they will be ready to treat new viruses that emerge without delay and will be able to overcome the development of resistance.”

 

“We need to develop this next generation of drugs now and have them on the shelves in order to be ready for the next pandemic threat—and there will be another one, for sure,” added Kirshenbaum. 

 

Drawing inspiration from our immune systems

Our innate immune system combats pathogens by producing antimicrobial peptides, the body’s first line of defense against bacteria, fungi, and viruses. Most viruses that cause disease are encapsulated in membranes made of lipids, and antimicrobial peptides work by disrupting or even bursting these membranes.

 

While antimicrobial peptides can be synthesized in the lab, they are rarely used to treat infectious diseases in humans because they break down easily and can be toxic to healthy cells. Instead, scientists have developed synthetic materials called peptoids, which have similar chemical backbones to peptides but are better able to break through virus membranes and are less likely to degrade.

 

“We began to think about how to mimic natural peptides and create molecules with many of the same structural and functional features as peptides, but are composed of something that our bodies won't be able to rapidly degrade,” said Kirshenbaum.

 

The researchers investigated seven peptoids, many originally discovered in the lab of Annelise Barron at Stanford, a co-author of the study. The NYU team studied the antiviral effects of the peptoids against four viruses: three enveloped in membranes (Zika, Rift Valley fever, and chikungunya) and one without (coxsackievirus B3).   

 

“We were particularly interested in studying these viruses as they have no available treatment options,” said Patrick Tate, a chemistry PhD student at NYU and the study’s first author. 

 

How peptoids disrupt viral membranes and avoid other cells

The membranes surrounding viruses are made of different molecules than the virus itself, as lipids are acquired from the host to form membranes. One such lipid, phosphatidylserine, is present in the membrane on the outside of viruses, but is sequestered towards the interior of human cells under normal conditions.

 

“Because phosphatidylserine is found on the exterior of viruses, it can be a specific target for peptoids to recognize viruses, but not recognize—and therefore spare—our own cells,” said Tate. “Moreover, because viruses acquire lipids from the host rather than encoding from their own genomes, they have better potential to avoid antiviral resistance.”

 

The researchers tested seven peptoids against the four viruses. They found that the peptoids inactivated all three enveloped viruses—Zika, Rift Valley fever, and chikungunya—by disrupting the virus membrane, but did not disrupt coxsackievirus B3, the only virus without a membrane.

 

Moreover, chikungunya virus containing higher levels of phosphatidylserine in its membrane was more susceptible to the peptoids. In contrast, a membrane formed exclusively with a different lipid named phosphatidylcholine was not disrupted by the peptoids, suggesting that phosphatidylserine is crucial in order for peptoids to reduce viral activity. 

 

“We’re now starting to understand how peptoids actually exert their antiviral effect—specifically, through the recognition of phosphatidylserine,” said Tate. 

 

The researchers are continuing pre-clinical studies to evaluate the potential of these molecules in fighting viruses and to understand if they can overcome the development of resistance. Their peptoid-focused approach may hold promise for treating a wide range of viruses with membranes that can be difficult to treat, including Ebola, SARS-CoV-2, and herpes.

 

In addition to Kirshenbaum, Tate, and Barron, study authors include Vincent Mastrodomenico, Christina Cunha, and Bryan C. Mounce of Loyola University Chicago Medical Center; Joshua McClure of Maxwell Biosciences; and Gill Diamond of the University of Louisville School of Dentistry. 

 

The research was supported in part by the National Science Foundation (CHE-2002890 and NSF GRFP) and the National Institutes of Health (R35GM138199 and 1DP1 OD029517-01). Kirshenbaum is the Chief Scientific Officer for Maxwell Biosciences, a biotech company that has licensed patents originating from his lab at NYU. The company is seeking to commercialize these compounds and bring them to the clinic to advance human health.

 

---

JOURNAL

ACS Infectious Diseases

DOI

10.1021/acsinfecdis.3c00063 

SUBJECT OF RESEARCH

Cells

ARTICLE PUBLICATION DATE

2-Aug-2023

Mimicking the body’s own defenses to destroy enveloped viruses

Peer-Reviewed Publication

AMERICAN CHEMICAL SOCIETY

Just as bacteria can develop antibiotic resistance, viruses can also evade drug treatments. Developing therapies against these microbes is difficult because viruses often mutate or hide themselves within cells. But by mimicking the way the immune system naturally deals with invaders, researchers reporting in ACS Infectious Diseases have developed a “peptoid” antiviral therapy that effectively inactivates three viruses in lab tests. The approach disrupts the microbes by targeting certain lipids in their membranes.

Viruses are almost like biological “zombies.” They are not quite living or nonliving, and are only able to multiply within a host, such as our body’s cells. Oftentimes, the immune system naturally destroys the pathogens with special molecules such as antibodies.

Less-well-known members of the immune system’s defense force are small protein-like molecules called antimicrobial peptides. These peptides aren’t good drug candidates, though, as they’re expensive to make, are quickly eliminated from the body and can cause side effects. Instead, some researchers have mimicked their function with lab-made molecules called peptoids that aren’t easily degraded by the body and are more economical to produce. Previously, Annelise Barron’s team showed that certain peptoids could pierce and destroy the SARS-CoV-2 and herpes viruses. This time, joined by Kent Kirshenbaum and colleagues, the group wanted to see if the peptoids could inactivate three other “enveloped” viruses enclosed within membranes — Zika, Rift Valley fever and chikungunya virus — as well as one that lacks a membrane envelope, coxsackie B3. No treatments currently exist for infections caused by these microbes.

The peptoids used in these experiments included three of the linear peptoids previously studied by Barron’s team, as well as four new circularized versions with increased antiviral activity. The researchers created model virus membranes using common lipids, including phosphatidylserine (PS). Membranes were disrupted most effectively when PS was present in higher concentrations, suggesting that the peptoids target it specifically. Though both human and viral membranes contain the lipid, it’s distributed differently in each instance, allowing an antiviral to preferentially attack the invader instead of the host. Next, the team incubated the peptoids with whole, infectious virus particles. Again, each worked to a different extent on the three enveloped viruses: some disrupted all three, some only one. However, none of the peptoids could inactivate the non-enveloped coxsackie B3 virus, showing that the mechanism of action hinges on the presence of the viral envelope. The team says that understanding this mechanism could inform the design of future peptoid-based antiviral treatments, and could be used to create drugs already armed against the next emerging viral threat.

The authors acknowledge funding from the National Science Foundation, the National Institutes of Health, Stanford University’s Discovery Innovation Fund, the Cisco University Research Program Fund, the Silicon Valley Community Foundation, and Dr. James Truchard and the Truchard Foundation. Kirshenbaum is the Chief Scientific Officer for and has material financial interests in Maxwell Biosciences, which is working to commercialize peptoid oligomers as anti-infective agents.

The paper’s abstract will be available on Aug. 2 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acsinfecdis.3c00063

For more of the latest research news, register for our upcoming meeting, ACS Fall 2023. Journalists and public information officers are encouraged to apply for complimentary press registration by completing this form.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

Follow us: Twitter | Facebook | LinkedIn | Instagram

---

JOURNAL

ACS Infectious Diseases

DOI

10.1021/acsinfecdis.3c00063 

ARTICLE TITLE

Peptidomimetic Oligomers Targeting Membrane Phosphatidylserine Exhibit Broad Antiviral Activity

ARTICLE PUBLICATION DATE

2-Aug-2023