Chinese scientists discover new strategy for early control of new coronavirus infection
In the face of the constantly mutating new crown virus, traditional coping methods seem to be stretched.
Is there any simple and practical means to combat the current new crown epidemic?
After in-depth research, the team of Professor Huang Bo and Professor Qin Chuan of the Chinese Academy of Medical Sciences found that targeting alveolar macrophages is an effective strategy for early control of new coronavirus infection, and found two commonly used clinically old drugs through the new coronary pneumonia mouse model .
Relevant research results were published online in the international academic journal "Signal Transduction and Targeted Therapy".
"This research can not only provide a safe and effective treatment plan for new coronary pneumonia, but also a bold attempt to 'reuse old drugs' and provide a new idea for screening new coronary treatment drugs." On April 7, Huang Bo emphasized in an interview with a reporter from Science and Technology Daily.
Alveoli, like balloons, are the basic structural units of the lungs.
The inner surface of the alveoli is called the pulmonary surfactant layer, which consists of a thin layer of lipids and proteins that keep the alveoli in a stretched state.
At the same time, this lipid membrane can isolate the outside world from the inside of the body. Blood drug molecules, including antibodies, have no ability to pass through the alveolar surface active layer.
However, the initial invasion site of the new coronavirus is the alveoli, so how does it break through the "isolation" under the body's layers of defense?
In this regard, Huang Bo explained that although the alveolar surface active layer isolates the outside world from the inside of the body, our immune system has a class of professional phagocytes, called macrophages, which penetrate the alveolar surface active layer and can It engulfs the particles and microorganisms contained in the inhaled air, thereby maintaining the cleanliness of the alveoli.
"Therefore, once the new coronavirus enters the alveoli, the alveolar macrophages use the cell membrane on their surface to wrap the virus particles and swallow them into the cytoplasm. This virus-encapsulated vesicle is called endosome." Huang Bo said that endosomes can deliver viral particles to lysosomes, a waste disposal site in the cytoplasm, where they can be broken down into amino acids, nucleotides, etc. for reuse by cells.
However, the new coronavirus can take advantage of the specific state of alveolar macrophages to escape from endocytosis and in turn use macrophages for self-reproduction.
Huang Bo said that this process depends on a proteolytic enzyme (CTSL) in the endosome and the pH of the endosome cavity.
At acidic pH, CTSL is activated to hydrolyze the spike protein of the new coronavirus, so that the viral genetic material RNA is released into the cytoplasm to initiate virus replication and amplification.
Under normal physiological conditions, the pH of alveolar macrophage endosomes is alkaline, and the new coronavirus engulfed by it is sent to lysosomes for degradation, so that the body shows no symptoms or milder symptoms.
Based on this, through a drug screening experiment in mice with new coronary pneumonia, Huang Bo's team found two commonly used clinical drugs to block the escape of the new coronavirus from the endosomes of alveolar macrophages.
"Clinically, bisphosphonates such as alendronate (ALN) are used to treat osteoporosis by targeting macrophages; the glucocorticoid drug dexamethasone (Dex) is a commonly used anti-inflammatory drug. "We found that Dex and ALN can synergistically block viral escape from endosomes by targeting CTSL expression and endosome pH, respectively," said Bo Huang.
Huang Bo said that the effect of such a combined treatment is achieved through the local administration route of nasal spray, and systemic administration is difficult to produce an effect due to the obstruction of the alveolar surface active layer.
At the same time, this combination can also play a hormonal anti-inflammatory effect.
This spray therapy is simple, safe, low-cost, and easy to popularize and use. It is a new strategy for early control of 2019-nCoV infection worthy of further in-depth study.
Our reporter Lu Chengkuan