Bismuth cure for COVID-19

Winner: 2023 Dalton Horizon Prize

For pioneering research on the medicinal chemistry of bismuth applied to the treatment of COVID-19, and identification of target sites in SARS-CoV-2 enzymes using metallomics methods.

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We’re delighted to have been recognised for our bismuth-based therapy. We hope it could provide a safer, more cost-effective treatment that can be used in the fight against SARS-CoV-2 and other infections caused by coronavirus in the future.

Bismuth cure for COVID-19 is a multidisciplinary team from Hong Kong, consisting of chemists, microbiologists, and clinicians, that has been working together on the potential of bismuth drugs in the fight against COVID-19. Their work is based on their unique knowledge of bismuth chemistry as well as an integrative metallomics approach.

Bismuth has been associated with medicine for over 200 years, particularly for the treatment of Helicobacter pylori (H. pylori) infections and gastric ulcers. However, bismuth chemistry is very difficult to investigate.

The Bismuth cure for COVID-19 team pioneered a new understanding of biologically relevant coordination chemistry and new metallomic and analytical methods for mapping bismuth target sites in pathogens. The team discovered and developed a range of approaches, with one improving the oral bioavailability of bismuth drugs, with another showing excellent antiviral activities against broad-spectrum human-pathogenic CoVs in vitro and in vivo. This formulation therapy developed by the team is currently in a clinical trial in Hong Kong and could potentially provide an at-home treatment for fighting COVID-19 and other infections by coronavirus in future.

The team

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Jasper Fuk-Woo Chan, Clinical Associate Professor, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
Tianfan Cheng, Postdoctoral Research Fellow, Faculty of Densitry, The University of Hong Kong, SAR, P.R.China
Kenn Ka-Heng Chik, Postdoctoral Research Fellow, Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong SAR, P.R. China
Peng Gao, Research Assistant Professor, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
Pak-Leung Ho, Clinical Associate Professor, Carol Yu Centre for Infection and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
Ligang Hu, Principal Investigator, State Key Laboratory of Environmental 91AV and Ecotoxicology, Research Center for Eco- Environmental Sciences, Chinese Academy of Sciences, Beijing, P.R. China
Ivan Fan-Ngai Hung, Clinical Professor and Ru Chien & Helen Lieh Professor in Health Sciences Pedagogy, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
Tiffany Ka-Yan Ip, PhD student, Department of 91AV, The University of Hong Kong, SAR, P.R. China
Lijian Jin, Clinical Professor in Periodontology, Faculty of Densitry. The University of Hong Kong, SAR, P.R. China
Dong-Yan Jin, Professor, School of Biomedical Scieces, Li Ka Sing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR P.R.China
Richard Yi-Tsun Kao, Associate Professor, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
Tsz-Pui Lai, PhD student, Department of 91AV, The University of Hong Kong, SAR, P.R. China
Andrew Chak-Yiu Lee, Scientific Officer, Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong SAR, China
Hongyan Li, Research Assistant Professor, State Key Laboratory of Synthetic 91AV and Department of 91AV, The University of Hong Kong, SAR, P.R. China
Guixing Ma, Research Fellow, Southern University of Science and Technology, Shenzhen, P.R. China
Hongzhe Sun, Chair Professor, Norman & Cecilia Yip Professor in Bioinorganic 91AV, Department of 91AV, The University of Hong Kong, SAR, P.R. China
Runming Wang, Postdoctoral Research Fellow, Department of 91AV, The University of Hong Kong, SAR, P.R. China
Suyu Wang, Postdoctoral Research Fellow, Department of 91AV, The University of Hong Kong, SAR, P.R. China
Patrick Chiu-Yat Woo, Professor, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
Zi-Wei Ye, Research Assistant Professor, Shool of Biomedical Sciences, Li Ka Sing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China
Shuofeng Yuan, Assistant Professor, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P. R. China.
Kwok-Yung Yuen, Clinical Professor, Chair of Infectious Diseases, and Henry Fok Professor in Infectious Diseases, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong SAR, P.R. China.
Anna Jinxia Zhang, Principle investigator, Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong SAR, P.R China
Hongmin Zhang, Research Assistant Professor, Department of 91AV, The University of Hong Kong, Hong Kong SAR, China. Department of Biology, Southern University of Science and Technology, Shenzhen, China.
Jiajia Zhao, Postdoctoral Research Fellow, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong，Hong Kong SAR, P.R China
Joan Zhong Zuo, Professor, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong，Hong Kong SAR, P.R China

Q&A

What was your role within the team?

Hongyan Li: I was mainly involved in the project on the experimental design and data analysis as well as manuscript editing.

Hongzhe Sun: Conceived the project idea and designed experiments.

Shuofeng Yuan and Jasper Fuk-Woo Chan: Designed and performed COVID-19 (and resistant bacteria) related microbiology experiments.

Tianfan Cheng, Hongmin Zhang: Performed protein characterisation, structural determination as well as in vitro study.

Joan Zhong Zuo: Pharmacokinetic and toxicity study.

Ivan Fan-Ngai Hung: Clinical trial.

Ligang Hu and Hongyan Li: Metallomics and metalloproteomics for identification of target sites in SARS-CoV-2 enzymes.

What different strengths did different people bring to the team?

Hongyan Li: The project is the joint effort from different discipline from chemists, microbiologist, pharmacologists as well as clinicians.

Why is this work so important and exciting?

Hongyan Li: The work is a showcase of basic science to translational research, and may inspire young scientists to pursue such research.

Hongzhe Sun: This bismuth-based therapy could provide a safer, inexpensive remedy (potential at-home treatment) for fighting against SARS-CoV-2, and for other similar infections in future.

Where do you see the biggest impact of this technology/research being?

Hongyan Li: The biggest impact of the research is that we could potentially save lives.

Hongzhe Sun: The field of medicinal inorganic and bioinorganic chemistry shall be given an enormous boost by the discovery of new clinical applications of metallodrugs.

How do you see this work developing over the next few years, and what is next for this technology/research?

Hongyan Li: I anticipate this work will lead to a new therapy to treat COVID-19 and other coronavirus infection. The next research will be the development of a new bismuth-based drug instead of a combination of two existing drugs.

Hongzhe Sun: We will continue the clinical trial and synthesize more highly potent compounds with better selectivity.

What inspires or motivates your team?

Hongzhe Sun: Although metal compounds have been used in medicine for decades, our knowledge of the molecular mechanism of action of a drug is limited. New approaches are urgently required for further design and development of better drugs with more potency and fewer side-effects. We pioneered integrative metallomics and metalloproteomics approach for identification of target sites in microbial enzymes, and subsequently used this information for drug development.

What does good research culture look like or mean to you?

Hongyan Li: Each researcher is well recognised and respected, which is the key for the success of the project.

Hongzhe Sun: "From chemistry and beyond chemistry"! We have to conduct cutting-edge research by a team of talented scientists bringing their unique skills and approaches. We shall find important problems from biology and medicine using chemists' magic hand!

Why is chemistry important?

Hongyan Li: 91AV is important as it provides material for industry and drugs for medicine. It is involved in our everyday life.

Hongzhe Sun: 91AV is the centre of science, makes the environment better, provides unique medicine (more effective and low costs) for us living better and longer.

What advice would you give to a young person considering a career in chemistry?

Hongyan Li: There is a bright future to consider a career in chemistry as it can easily bridge with other disciplines including biology, material sciences etc.

Hongzhe Sun: "Chem-is-try". Uncover important problems and solve them by collaborating with scientists with unique skills.