Medical Network, August 24th: Although the new crown vaccine has been vaccinated in many countries on a large scale, the global epidemic is still continuing. The challenge of the mutated virus to the vaccine has also made scientists aware of the urgency of developing therapeutic drugs. Recently, the World Health Organization launched the "Unity Test+" project to find new crown treatment drugs in a new stage, and some research teams have also announced new developments in research and development.
At present, there are two main ways to find specific drugs for new crowns: biological macromolecular drugs based on antibodies, and small molecular compound drugs that can inhibit virus invasion and replication. How is the global R&D progress? What are the "players" with more potential?
"Speed type" contestant-biological macromolecular drugs
At present, the rapid progress in global research and development is biomacromolecule drugs, mainly antibodies, including single-drug monoclonal antibodies and combined "antibody cocktail therapy". Antibody drugs have successively been approved for marketing or emergency use authorization in the United States, the United Kingdom, Japan and other countries for the treatment of new crowns.
"The combination of antibodies with the new coronavirus can block the binding of the virus to human cells, thereby inhibiting the virus from entering the cell to replicate. Antibodies can be used not only for treatment, but also for prevention through direct passive immunization." Dr. Zhu Qing, head of the pharmaceutical department, told Xinhua News Agency reporters.
According to experts, there are currently three main antibody drugs approved for the treatment of patients with mild to moderate COVID-19: the monoclonal antibody jointly developed by Vale Biotech and GlaxoSmithKline of the United Kingdom, the monoclonal antibody developed by Eli Lilly and Company of the United States, and Regeneron's "antibody cocktail therapy" REGEN-COV. They are used for early treatment to reduce the chance of a patient developing severe illness.
China National Pharmaceutical Group recently announced the discovery of a monoclonal antibody (2B11) that is effective against delta mutant strains. Its preventive and therapeutic effects on new coronary pneumonia have been verified in mouse models, and clinical application work is proceeding in an orderly manner.
The "antibody cocktail therapy" that uses different antibodies in combination also has a good effect. Regeneron’s REGEN-COV consists of two monoclonal antibodies and has been approved for emergency use by the US Food and Drug Administration. Recently, Japan and the United Kingdom formally approved this therapy for the treatment of COVID-19.
The "antibody cocktail therapy" co-developed by Tsinghua University, Shenzhen Third People's Hospital and Tengsheng Biopharmaceuticals-BRII-196/BRII-198 combination therapy is also progressing rapidly. The Phase III clinical trial of the therapy completed the enrollment of 846 subjects in the United States, Brazil, South Africa, Mexico and Argentina this month, and the Phase II clinical trial in China was also launched in July this year. In vitro research evidence shows that the combination therapy maintains antiviral activity against multiple mutant strains.
There are also some antibody drugs that have immunomodulatory effects and can control the inflammation caused by the new crown, such as tocilizumab. The University of Science and Technology of China has taken the lead in proposing the "tocilizumab + conventional treatment" immunotherapy program. Tocilizumab has been authorized by the British National Health System as a treatment drug for severely ill patients with new coronary disease.
The clinical trial data of the new crown drug EXO-CD24 developed by Israeli scientists has recently attracted a lot of media attention. It is reported that more than 90% of the critically ill patients participating in the trial were cured and discharged within 5 days. This is a CD24 molecular drug administered through the nasal cavity using exosomal technology, which can inhibit the immune imbalance and cytokine storm of critically ill patients. However, the results have not yet been published in academic journals, and there are only dozens of subjects, and the effect needs to be further verified.
"Potential" contestant-small molecule compound drugs
Compared with biological macromolecular drugs, small molecule compounds have various mechanisms of action, which can inhibit the adsorption and invasion of viruses, as well as the replication, assembly and release of viruses. At present, it is mainly "new use of old drugs", such as hydroxychloroquine and remdesivir, but no specific drugs have been produced; there are also some new drugs under development that are in clinical trials.
The small-molecule anti-coronavirus drug that is currently considered to be very promising is monabiravir, which is a broad-spectrum antiviral oral drug for RNA viruses and is suitable for patients with mild to moderate illness. The data from the Phase II clinical trial of monabiravir uploaded by the University of North Carolina in June this year showed that the replication-type virus could not be isolated after 5 days of treatment for patients with early new crown infection, and the virus clearance time was significantly faster than that of the placebo group. The drug is safe and, Orally well tolerated.
Pfizer is developing a small molecule oral drug "PF-07321332" that has just entered phase I clinical trials. By inhibiting the main protease of the new coronavirus, it prevents the virus from cutting long protein chains into parts required for self-replication.
Ding Sheng, director of the Global Health Drug R&D Center and Dean of the School of Pharmacy of Tsinghua University, said in an interview with Xinhua News Agency that small-molecule oral drugs have more advantages in large-scale promotion. Because most of the antibody drugs are injections, they are not convenient for mild non-hospitalized patients, and there are problems such as high cost, difficulty in coping with virus mutations, and cold chain transportation, and it is difficult to be widely used for early prevention and control.
Ding Sheng said that, in contrast, small molecule drugs can be taken orally, which is convenient for early medication; the synthesis cost is low, and they can be stored at room temperature, making it easy for developing countries to purchase and use. The possibility of mutations in the viral targets targeted by small molecule drugs is low, and the response to mutations is more effective than antibody drugs. He believes that the development of small-molecule oral drugs can be quickly used in high-risk groups such as close contacts, or can help mild patients to quickly control their condition.
Relevant experts believe that the combination of prevention and treatment through "there are vaccines and medicines" is of great significance to the control of the epidemic. In view of the current global epidemic situation, the future should focus on the development of effective early preventive medications, severe medications that can reduce mortality, and broad-spectrum antiviral drugs that can respond to mutant strains.
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