Breakthrough in coronavirus fight: HKUMed develops powerful bispecific inhibitor to combat a wide range of coronaviruses

The University of Hong Kong

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A research team, led by Professor Chu Hin (right) and Dr Vivian Shuai Huiping (middle), has discovered a powerful bispecific inhibitor capable of combating a wide range of existing human-pathogenic coronaviruses. This promising inhibitor, named TMP1, offers hope for more effective and resilient treatments against future outbreaks.

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Credit: The University of Hong Kong

Researchers from the Department of Microbiology, School of Clinical Medicine, LKS Faculty of Medicine of the University of Hong Kong (HKUMed) and the InnoHK Centre for Virology, Vaccinology and Therapeutics (CVVT), in collaboration with Sichuan University, have discovered a powerful bispecific inhibitor capable of combating all existing human-pathogenic coronaviruses, including those resistant to existing treatments like Paxlovid. This promising inhibitor, named TMP1, offers hope for more effective and resilient treatments against future outbreaks. A patent has been filed for further exploration in clinical applications. The study’s findings were published in the peer-reviewed scientific journal Nature Communications [link to publication].

Potential high risk of future animal-to-human coronavirus outbreaks
Over the past two decades, coronaviruses have led to three major outbreaks, including COVID-19 pandemic. Recently, scientists have discovered new viruses transmitted from animals to humans, which means the risk of another outbreak remains significant. This ongoing threat highlights the urgent need for better ways to prevent and treat these dangerous viruses.

‘One promising target for developing anti-coronavirus treatments is TMPRSS2, a host enzyme that the virus uses to enter human cells. However, existing TMPRSS2 inhibitors used to treat infected patients, such as camostat, have limitations. They are not easily absorbed when taken orally and are quickly broken down in the body, which reduces their effectiveness,’ explained Professor Chu Hin, Gallant Ho Outstanding Young Professor and Associate Professor in the Department of Microbiology, School of Clinical Medicine at HKUMed.

Another appealing antiviral target is Coronavirus Mpro, which is essential for the virus to replicate. Paxlovid, a drug developed to target SARS-CoV-2 Mpro, has shown strong antiviral potency. But Professor Chu remarked, ‘The virus can mutate rapidly, leading to variants that are resistant to current drugs, making treatment more challenging.’

A novel bispecific inhibitor to target multiple coronaviruses
To overcome these challenges, the research team aimed to develop an orally available inhibitor that can simultaneously target the coronavirus Mpro and the host TMPRSS2, providing bispecific protection to coronavirus infections with high potency.

Using a new chemical synthesis approach, the research team screened for potent small molecules capable of suppressing the enzymatic activity of SARS-CoV-2 Mpro and TMPRSS2. The most promising candidates from the primary screening were chemically optimised to produce a new bispecific inhibitor, TMP1, which was further tested to assess its stability in the body, antiviral effectiveness and sensitivity to drug-resistant mutants.

Professor Chu elaborated, ‘Our results showed that TMP1, the new bispecific inhibitor, has broad-spectrum antiviral efficacy against all known human-pathogenic coronaviruses, including the highly pathogenic SARS-CoV-2, SARS-CoV-1 and MERS-CoV. Additionally, TMP1 was able to protect hamsters from SARS-CoV-2 transmission. TMP1 binds to the enzymatic pocket of Mpro at distinct mechanisms when compared with existing drugs like Nirmatrelvir. This suggests that it can potentially overcome some forms of drug resistance. In fact, TMP1 demonstrated robust protection against Paxlovid-resistant SARS-CoV-2 mutants in infected cells and animals.’

Dual-target drug offers more effective protection against coronaviruses
This study is the first to demonstrate that potent, broad-spectrum protection against coronavirus infections can be achieved by simultaneous targeting of both Mpro and TMPRSS2. ‘Unlike conventional mono-target antiviral drugs, the bispecific approach opens new avenues for therapeutic design,’ said Professor Chu. ‘It paves the way for the development of next-generation antivirals that are not only more effective but also less prone to resistance.’

The significance of the research has been recognised internationally. The research earned a Silver Prize in the 50th International Exhibition of Inventions of Geneva 2025. It also achieved success at the 10th International Invention Innovation Competition in Canada, iCAN 2025, and won a gold medal and two special awards.

About the research team
The research team was led by Professor Chu Hin, Gallant Ho Outstanding Young Professor and Associate Professor, and Dr Vivian Shuai Huiping, Research Assistant Professor, both from the Department of Microbiology, School of Clinical Medicine, HKUMed, in collaboration with the InnoHK Centre for Virology, Vaccinology and Therapeutics, and Professor Yang Shengyong and Professor Lei Jian from Sichuan University.

TMP1, the new bispecific inhibitor, has broad-spectrum antiviral efficacy against multiple human-pathogenic coronaviruses, including the highly pathogenic SARS-CoV-2, SARS-CoV-1 and MERS-CoV.

Credit

The University of Hong Kong

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Journal

Nature Communications

DOI

10.1038/s41467-025-60832-z 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

An orally available Mpro/TMPRSS2 bispecific inhibitor with potent anti-coronavirus efficacy in vivo

 

‘How drunk do you feel?’: Ozempic, Wegovy may help reduce alcohol use, Virginia Tech researchers find

Scientists report that people taking diabetes and weight-loss medications may experience delayed effects after drinking alcohol

Virginia Tech

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Fralin Biomedical Research Institute at VTC researchers found that after a cocktail, participants in a small, pilot study who were taking medications for diabetes and weight loss saw delayed effects from alcohol.

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Credit: CLAYTON METZ/Virginia Tech

There’s mounting evidence that popular drugs prescribed for diabetes management and weight loss — better known by trade names like Ozempic and Wegovy — could be effective in reducing alcohol use.

A study from the Fralin Biomedical Research Institute at VTC, released this month in Scientific Reports, found that these types of GLP-1 agonists slow the speed at which alcohol enters the bloodstream, which also slows the effects on the brain.

“People who drink know there’s a difference between nursing a glass of wine and downing a shot of whiskey,” said Alex DiFeliceantonio, assistant professor and interim co-director of the FBRI’s Center for Health Behaviors Research.

A standard serving of either has 0.6 ounces of alcohol, but the shot brings a rapid increase in blood-alcohol content. It feels different because of the way the body handles alcohol over time.

“Why would this matter? Faster-acting drugs have a higher abuse potential,” DiFeliceantonio said. “They have a different impact on the brain. So if GLP-1s slow alcohol entering the bloodstream, they could reduce the effects of alcohol and help people drink less.”

More than half of U.S. adults drink alcohol, and roughly one in 10 has alcohol use disorder. Long-term, chronic alcohol use is associated with health-related illnesses such as high blood pressure, cancer, and heart and liver disease. In January, U.S. Surgeon General Vivek Murthy released an advisory highlighting alcohol use as the third leading preventable cause of cancer, after tobacco use and obesity.

Despite consuming similar doses of alcohol calculated to increase breath alcohol concentration to approximately 0.08 percent, concentration increased more slowly in participants taking semaglutide, tirzepatide, or liraglutide. Participants in that group also reported feeling less intoxicated on subjective measures.

The research, supported by funding from Virginia Tech’s Fralin Biomedical Research Institute, sought to better understand the physical and subjective experience of alcohol traveling through the body of someone taking a GLP-1. The study provides important early data to guide the design of larger, more rigorous studies testing whether GLP-1 drugs can help reduce alcohol use.

Twenty participants with a BMI of 30 or greater, half on a maintenance dose of GLP-1s and half taking no medication, were recruited from Roanoke, Virginia, and surrounding areas. They fasted before arriving for the study, then they were given a snack bar to standardize caloric intake and stomach contents.

Researchers gathered blood pressure, pulse, breath alcohol concentration, and blood glucose levels. Ninety minutes later, participants were served an alcoholic beverage that had to be consumed within 10 minutes. Researchers then measured breath alcohol and participants answered questions about cravings, appetite, alcohol effects, and taste. For example, they were asked to rate, on a scale of zero to 10, “How drunk do you feel right now?” This was repeated three times over 60 minutes.

The participants on GLP-1s consistently reported feeling less intoxicated.

Following the session, participants remained in a recovery room as the alcohol was metabolized. Breath alcohol was measured every 30 minutes, blood glucose was measured twice, and three hours after the session participants again answered subjective questions. After four hours, a breath alcohol content below .02 percent, and the study physician’s approval, the participant was OK’d to leave.

“Other medications designed to help reduce alcohol intake” — naltrexone and acamprosate — “act on the central nervous system,” said DiFeliceantonio, the study’s corresponding author. “Our preliminary data suggest that GLP-1s suppress intake through a different mechanism.”

The drugs slow gastric emptying, which can lead to a slower rise in blood alcohol.

The idea for the study initially bubbled up during a Fralin Biomedical Research Institute faculty retreat and was led by Warren Bickel, professor and director of the Addiction Recovery Research Center, who died in 2024.

It built on an analysis of social media posts on the community network Reddit, in which users reported reduced cravings for alcohol when taking drugs intended to treat type 2 diabetes and obesity. 

“His guidance shaped every stage of this research — from the initial idea to its final form — and his passion for scientific discovery continues to inspire me every day,” said Fatima Quddos, a graduate researcher in Bickel’s lab and the first author on both studies.

“Bickel’s work had long focused on what happens when you delay rewards, so we asked, ‘What if GLP-1s affect how the body handles alcohol?’” DiFeliceantonio said. “Ending this project was bittersweet, because it was my last collaboration with him.”

“He was always asking, ‘How do we help people the fastest?’ Using a drug that’s already shown to be safe to help people reduce drinking could be a way to get people help fast,” DiFeliceantonio said.

While this was a pilot study, researchers said the findings showed clear differences between groups and provide early data that support larger trials testing the drugs as a therapy for people who want to reduce their alcohol use.

“As a recent graduate, I’m deeply inspired by the potential this research holds — not only for advancing our scientific understanding, but also for paving the way toward future therapies,” said Quddos, who earned her doctorate from Virginia Tech’s Translational Biology, Medicine, and Health Graduate Program in May. “The possibility of offering new hope to individuals struggling with addiction is what makes this work so meaningful.”

 

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Journal

Scientific Reports

DOI

10.1038/s41598-025-17927-w 

Method of Research

Experimental study

Subject of Research

People

Article Title

Physiological and perceptual effects of GLP-1 receptor agonists during alcohol consumption in people with obesity: a pilot study

Article Publication Date

15-Oct-2025

 

Divine punishment as an ancient tool for modern sustainability

Fear of supernatural punishment could reduce environmental harm and promote sustainable relationships between human societies and nature

Peer-Reviewed Publication

Doshisha University

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In Japanese folklore, tengu are supernatural beings that inhabit mountains and deep forests. Traditionally seen as guardians of these sacred spaces, they punish those who show arrogance, disrespect nature, or defile holy sites. Tengu are both feared and revered, reminding people to live in harmony with the natural and spiritual worlds.

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Credit: Yoshikazu TAKADA from Openverse

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Throughout human history, many cultures have developed belief systems that tied nature to the supernatural, fostering practices that preserved and sustained their environments. Forest spirits, river gods, or deities were often seen as guardians of natural domains, and exploiting nature carried the risk of retaliation from these beings. Today, with mounting concerns over the overexploitation of the world’s natural resources, can bringing back some of these supernatural beliefs help deter such behaviors?

The underlying idea is that fear of retribution from a supernatural entity might deter people more effectively than modern penalties, which require costly state enforcement. To explore this possibility, researchers from Doshisha University and collaborating institutions turned to evolutionary game theory. This framework examines how behaviors and beliefs spread or fade within a population depending on the conditions and benefits they provide.

The study, published in Humanities and Social Sciences Communications on October 15, 2025, was led by Dr. Shota Shibasaki from the Faculty of Culture and Information Science at Doshisha University, Japan. It also included Dr. Yo Nakawake from Japan Advanced Institute of Science and Technology, Dr. Wakaba Tateishi from Hokkaido Musashi Women’s University, Dr. Shuhei Fujii from Kokugakuin University, and Dr. Ryosuke Nakadai from Yokohama National University and Research Institute for Humanity and Nature.

Dr. Shibasaki’s own cultural background inspired him to undertake research in this direction. As Dr. Shibasaki explains, “I am interested in how human culture, including supernatural beliefs, affects the natural environment and vice versa. Growing up in Japan, I am familiar with folklore that portrayed nature as sacred and spiritually guarded. These stories left a lasting impression on me and sparked my curiosity about their societal functions. As a researcher, I hoped to bridge the gap between the abstract mathematical model and my cultural experiences, ultimately contributing to a more holistic understanding of human–nature interactions.”

To investigate, the researchers developed a mathematical model that combines three closely linked elements: the degree to which people believe in supernatural punishment, the intensity with which they exploit natural resources, and the actual availability of those resources in the environment. These elements constantly influence one another. When people overexploit resources, the environment becomes depleted. As resources decline, the benefits of further exploitation diminish. Meanwhile, if people believe in supernatural punishment, they are less likely to overexploit in the first place, which allows resources to recover.

Analysis conducted using the model showed that supernatural punishments are effective under two conditions. First, the fear of supernatural punishment must be strong enough to outweigh the short-term gains of overusing resources, encouraging restraint. Second, the punishment should not be so extreme that people are unwilling to adopt the belief at all. When both conditions are met, the belief can spread through a community and act as an enforcement system, without requiring human policing.

But could such beliefs really take hold in modern societies? The researchers suggest that it is possible because human psychology naturally supports the spread of religious ideas. Stories of forest spirits or river gods tend to be memorable and widely shared. Additionally, people frequently imitate the beliefs of prestigious figures, so if respected leaders or religious authorities endorse such ideas, others may follow.

This has practical implications for conservation efforts. In communities where folklore and cultural traditions remain strong, stories of supernatural punishment could be used to encourage environmental protection. Policymakers might also work with existing traditions where formal laws or enforcement are limited. Overall, the study suggests that sustainability efforts in modern society can also be shaped by culture, belief, and human psychology.

“Ultimately, this work contributes to a broader understanding of how human societies can have more harmonious relationships with nature—not just through regulation or technology but also through supernatural belief and culture,” concludes Dr. Shibasaki.
 

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About Assistant Professor Shota Shibasaki from Doshisha University, Japan
Shota Shibasaki is an Assistant Professor at the Faculty of Culture and Information Science, Doshisha University. He earned his Ph.D. in Life Sciences from the University of Lausanne in 2022. His research explores the complex dynamics of ecology and evolution, focusing on how cooperation, species interactions, and cultural evolution shape biological and social systems. Using mathematical models, data analysis, and experiments, he has studied cooperation in microbes, biodiversity in changing environments, and the interplay between culture and nature.

Funding information
The study was supported by Research Institute for Humanity and Nature (RIHN: a constituent member of NIHU) Project No. RIHN14210183 to Ryosuke Nakadai, and partially by the Foundation for the Fusion of Science and Technology to Shota Shibasaki.

Media contact:
Organization for Research Initiatives & Development
Doshisha University
Kyotanabe, Kyoto 610-0394, JAPAN
E-mail：jt-ura@mail.doshisha.ac.jp

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Journal

Humanities and Social Sciences Communications

DOI

10.1057/s41599-025-05734-7 

Method of Research

Computational simulation/modeling

Subject of Research

Not applicable

Article Title

Fear of supernatural punishment can harmonize human societies with nature: an evolutionary game-theoretic approach

Article Publication Date

15-Oct-2025