Science and Technology Daily: COVID-19 drug research and development: strengthening China’s power in new drug creation
In the research and development of new coronavirus drugs, my country's new drug research and development capabilities have been strengthened and its strength has gradually emerged. More than 50 COVID-19 drugs have been approved to enter the clinical trial stage, new anti-epidemic "three-party" traditional Chinese medicine has been approved for marketing, and my country's first anti-COVID-19 drug has been approved for marketing... After more than two years of hard research and development, China's original COVID-19 drugs are or will soon participate in the battle to end the COVID-19 pandemic.
The latest statistics from the State Food and Drug Administration show that as of the end of February 2022, more than 50 COVID-19 drugs in my country have been approved to enter the clinical trial stage, a neutralizing antibody COVID-19 drug has been approved for marketing, and new anti-epidemic "tripartite" traditional Chinese medicines have been approved for marketing...
After more than two years of research and development by top scientific research teams around the clock, China's original new coronavirus drugs are or will soon participate in the battle to end the new coronavirus pandemic by blocking virus replication, blocking virus invasion, and adjusting the body's immunity.
Use scientific methods to explain the efficacy of traditional Chinese medicine
On March 2, 2021, the "three prescriptions" of traditional Chinese medicine, Qingfei Paidu Granules, Huashibaidu Granules, and Xuanfei Baidu Granules, which play an important role in the fight against the new coronavirus epidemic, were approved for marketing.
"These three prescriptions are all prescriptions that have been explored in practice and have been evaluated during use. They are indeed clinically effective." Zhang Boli, a representative of the National People's Congress, an academician of the Chinese Academy of Engineering, and the honorary president of Tianjin University of Traditional Chinese Medicine, said that traditional Chinese medicine believes that "good medicines come out of great epidemics", and on the basis of clinical practice By optimizing and combining classic prescriptions and adding experimentally effective traditional Chinese medicine components, we can develop new traditional Chinese medicines that can significantly improve symptoms, reduce the weight conversion rate, promote nucleic acid negative conversion and reduce sequelae. This is also a way to quickly screen, evaluate and develop new drugs.
Take Xuanfei Baidu Granules as an example. It is composed of five classic prescriptions, including Maxing Shigan Decoction and Qianjin Weijian Decoction. "At the same time, traditional Chinese medicine components selected through experiments are added to treat the new coronavirus symptomatically." Zhang Boli explained that for example, components of Polygonum cuspidatum have a significant effect on inhibiting the replication of coronavirus, while a certain component of Verbena has a very clear effect on inflammation of small airways, and adding it can enhance the efficacy.
In order to further use modern means to evaluate the efficacy of traditional Chinese medicine, Zhang Boli's team carried out network pharmacology research on Xuanfei Baidu Recipe, sorted out the effective compounds and target action pathways, analyzed and obtained functional relationships and mechanism predictions, and explained the mechanism of action of innovative traditional Chinese medicine in the treatment of COVID-19.
"Through experiments, we found that Xuanfeibaidu prescription has a certain effect in inhibiting the replication of coronavirus, but more importantly, it regulates the body's immune function so that the immune response caused by virus invasion is not over-activated and triggers a storm of inflammatory mediators." Zhang Boli said that for more than a year, the team has used modern means to answer a series of questions about the effective components of traditional Chinese medicine, action targets, and pharmacodynamic mechanisms, and used experimental data to answer a series of questions such as how traditional Chinese medicine can improve symptoms and control the rate of weight loss.
"After comprehensive analysis of drugs, targets and mechanisms of action, we found that the targets and mechanisms of the 'Three Medicines and Three Prescriptions' are different in different stages of COVID-19, such as mild, common and severe cases. This also explains why traditional Chinese medicine can play a role in fighting the new coronavirus at all stages." Zhang Boli said that using modern evaluation methods to clearly explain the mechanism of traditional Chinese medicine will be more conducive to conveying the efficacy of traditional Chinese medicine through the international discourse system and assisting global epidemic prevention and control.
Starting from clinical needs
The R&D and creation of new drugs are closely related to people's lives and health and directly meet people's life and health needs. "New drug research and development must be oriented to clinical problems, and only by identifying the starting point can we grasp the innovative direction of new drug creation." Academician Wang Chen, member of the National Committee of the Chinese People's Political Consultative Conference, vice president of the Chinese Academy of Engineering, and president of the Chinese Academy of Medical Sciences, said that the international new drug research and development path is generally based on clinical needs, the laboratory (through mechanism research) finds the target, and the company follows up (transformation) research. However, the source of my country's new drug research and development involves problems such as finding targets from foreign literature and conducting secondary innovations based on foreign original drugs.
"China has abundant clinical research resources, and many problems will be encountered clinically. These problems are the source of medical innovation." Wang Chen gave an example. A small molecule reagent drug required for respiratory diagnosis has not been developed in China, and industrial preparations have been used instead. It was not until clinicians and pharmaceutical experts cooperated in research and development that this problem was solved recently.
A large number of clinical needs are the "question bank" for medical innovation and development. There are still two problems in how to make good use of this "question bank".
On the one hand, clinicians lack the atmosphere to invest in scientific research. Wang Chen believes that doctors’ involvement in clinical research and taking on the responsibility of knowledge creation will promote original innovation in medicine and pharmacy in my country. On the other hand, my country's clinical resources have not been fully utilized. Wang Chen said that for example, among the global registered clinical studies, the number of registered studies in my country only accounts for about 3%. Medical innovation and research and development must adhere to the "four aspects", fully stimulate the willingness of clinicians to explore clinical needs, and be more deeply integrated into the entire ecological chain of medical research and development.
Embrace revolutionary changes in the pharmaceutical industry
"Life science is no longer just a matter for biologists. It includes the integrated development of physics, chemistry, mathematics, information science, materials science, engineering science and other disciplines, so that we can jointly promote the development of life science." said Chen Kaixian, an academician of the Chinese Academy of Sciences.
To welcome the revolutionary changes in the pharmaceutical industry, the entrepreneurial capabilities of our country's enterprises have gradually increased; the national science and technology plan has successively set up major special projects and key research and development plans related to new drug research and development in the layout. According to the latest data released by McKinsey in 2020, my country's new drug research and development accounts for 13.9% of the world's total, ranking in the second echelon.
In the research and development of new coronavirus drugs, my country's new drug research and development capabilities have been strengthened and its strength has gradually emerged. On December 8, 2021, my country’s first anti-COVID-19 drug, the novel coronavirus monoclonal neutralizing antibody ambavirumab and romisevirumab combination therapy, was approved for marketing. The combination drug was jointly developed by Tsinghua University, Shenzhen Third People's Hospital and Tengsheng Biopharmaceuticals.
Zhang Linqi, leader of the R&D team and professor at Tsinghua University School of Medicine, previously said that each laboratory has its own bright ideas and will select partners to join in the creation of new drugs based on the technology platform and accumulation previously owned by each laboratory.
Being prepared is one of the common features of my country's new coronavirus drug discovery and development teams, and the teams that finally withstood rounds of screening challenges have another characteristic: collaborative research and development. For example, the research and development of Azivudine, a domestically produced small molecule COVID-19 drug, has gathered the R&D strength of dozens of teams from real pharmaceutical companies, Chinese Academy of Medical Sciences and other companies, research institutes, and hospitals to carry out R&D cooperation across disciplines and fields, and jointly promote work including clinical trials, mechanism verification, etc.
It has become an industry consensus to further integrate innovation resources and strengthen the research and development transformation of new drug creation. To successfully fight the battle of R&D in core technologies, we need to further promote the strong alliances among Chinese enterprises, colleges and universities, and scientific research institutes.