Structure-Guided Discovery of Anti-Coronavirus Compounds
from Chinese Medicine Perspectives
Pathway and Biomarkers for COVID-19
Antiviral Evaluation Platform for Drug Discovery Against SARS-Cov-2
Structure-Guided Discovery of Anti-Coronavirus Compounds
Department of Physics
As a new laboratory, we are in some ways limited in our ability to organize a research program to study COVID-19. The opportunity perform research on COVID-19 came when my laboratory’s expertise in structural biology is called for in a joint effort to discover potential drugs to treat the disease. Knowing that we are doing our part in the laboratory helped us deal with the sense of helplessness while the virus ravages across the globe.
Visualising how drug molecules inactivate their target viral components is an important aspect of antiviral drug discovery for COVID-19. As part of a collaborative team with scientists from other universities in Hong Kong, we provide expertise in purifying viral components such as COVID-19 proteins and studying how drugs act on these targets. We are particularly interested in viral components that are essential in viral replication. These viral components allow the coronavirus to make more copies of themselves during infection. Our goal is to find drug molecules that will block the functions of these vital proteins. To visualize how the drugs work at the atomic level, we use protein X-ray crystallography to obtain 3-dimensional structures of protein-drug complexes. These 3D structural data give us insights into how potential drug molecules work on COVID-19 components and how we can improve the effectiveness of drug molecules.
Combating COVID-19 from Chinese Medicine Perspectives
The global pandemic of Coronavirus disease 2019 (COVID-19) has pressure on clinicians and scientists to find treatment or vaccine to handle the severe situation. The only therapeutic way currently is to symptom-based control, but not targeting on the virus. Existing treatment for the virus of COVID is non-effective. Chinese medicine are being explored for providing prevention, treatment and rehabilitative care to patients. In Chinese Medicine (CM), COVID-19 belongs to plague (疫病) with the etiology of epidemic factor exposure. CM treats different stages of mild, moderate, severe and critical cases based on clinical manifestation and individual symptoms. In Hong Kong, the pulmonary rehabilitation to improve lung function upon discharged patients has been proposed and supported by Chinese Medicine Department, Hospital Authority.
This is a multi-centered study that will be conducted in the government subsidized tri-partite CM out-patient clinics. The study includes two parts, one is the retrospective exploration of the body constitutions before the patients were diagnosed as COVID-19 and the identification of the clinical symptoms and syndrome diagnosis of COVID-19 patients, the other is the evaluation of individual-based Chinese herbal medicine effects on the clinical symptoms improvement, lung functions, and body constitution questionnaires. The pathway and biomarkers for COVID-19 from Prof. Cai Zongwei’s team and the establishment of Prof. Zhang Hongjie’s team also contributed to combat COVID-19. Future plan will focus on development of CM based new drugs for virus-based disease and the collaboration between CM and Western medicine.
Prof Zhongwei Cai
Dr Lin Zhu
Department of Chemistry
Faculty of Science
Collaborating with State Key Laboratory for Emerging Infectious Diseases in HKU, SKLEBA research team is investigating how cells respond to SARS-CoV-2 infection.
COVID-19 pandemic is caused by a virus named as SARS-CoV-2, which is the third coronavirus significantly threat human in the past two decades. However, before SARS broke out in 2002, coronavirus was generally considered as a harmless virus that only caused mild flu symptom. Consequently, little knowledge was available for this virus, particularly how the virus behaves once it enter the cells.
Collaborating with State Key Laboratory for Emerging Infectious Diseases in HKU, SKLEBA research team is investigating how cells respond to SARS-CoV-2 infection. Briefly, we examined cellular proteins and their abundance before and immediately after the infection of COVID-19, then screened the ones changed most. In this regard, it is hoped to identify novel proteins that affects by SARS-CoV-2. In theory, these proteins should be of vital importance to viral replication. If an appropriate medicine is available to specifically inhibit the protein activity, it could serve as a potential cue for COVID-19. Currently, we have identified a few candidate proteins that might be used by the virus immediately after infection. Experiments with some promising inhibitors are now on-going. SKLEBA has been awarded $1.2 million, by the Innovation and Technology Commission, to develop test kits based on biomarkers and COVID-19 antigens using nano-material. It is expected that the kit can directly assess the level of herd immunity and monitor the immune response that may help the vaccine development.
Prof Hongjie Zhang
School of Chinese Medicine
This project strives to establish an evaluation platform to discover novel antiviral agents against emerging and re-emerging viruses including the novel coronavirus SARS-CoV-2.
This project strives to establish an evaluation platform to discover novel antiviral agents against emerging and re-emerging viruses including the novel coronavirus SARS-CoV-2. Emerging and re-emerging viruses have constantly caused deadly diseases in human history. One of the deadliest viruses was the 1918 Spanish H1N1 influenza virus that killed approximately 40-80 million people. Over the past 40 years, there have been various of pandemic or epidemic diseases caused by emerging and re-emerging viruses such as HIV, SARS-CoV-2 and H1N1 influenza virus. HIV has killed approximately 32 million people since its discovery in 1981.
As of May 10, 2020, the current COVID-19 epidemic has already caused 280,594 deaths among over 4 million infected cases. Ebola virus outbreaks have occurred periodically since 1970s, their mortality rates have ranged among 40-90 %. These are just a few examples of the emerging and re-emerging viruses that have brought huge burdens on world economy and public health systems. Nonetheless, we human seem to be helpless as to their invasion. We have no curable drugs, nor vaccines to combat them. Fortunately, the nature has provided us a huge plant resource from where we may uncover therapeutic recipe to fight against the vicious viruses.
We are dedicated to discover novel antiviral agents from the medicinal and edible plants found in the regions of the Southeastern Asia. In the current project, we propose to establish a concise and safe evaluation system that is able to rapidly screen our plant sample library for discovery of novel antiviral agents that can be used as both preventative and therapeutic measurements for combating emerging and re-emerging viruses.