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.
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.
