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Facing to the constantly changing COVID-19, the traditional means of coping are somewhat not effective.
Professor Huang Bo and Qin Chuan team of CAMS(Chinese Academy of Medical Sciences) discovered that targeted alveolar macrophages were effective strategies for early control of COVID-19 infection, and found two commonly used drugs in the COVID-19 mouse model. Relevant research results are published online in the international academic journal, signal transduction and targeted therapy.
“This study not only provides a safe and effective treatment for COVID-19, but also a bold attempt to ‘use old drugs for new use’, providing a new way of thinking to choose drugs for COVID-19.” Huang Bo stressed in an interview with the reporter of science and technology daily On April 7th.
Like a balloon, an alveoli is the basic structural unit of the lung. The inner surface of the alveoli is called the pulmonary surfactant layer, which is composed of a thin layer of fat and protein to maintain the alveoli in an extended state. At the same time, this lipid membrane can isolate the outside from the inside of the body. Blood drug molecules, including antibodies, have no ability to pass through the alveolar surface active layer.
Although the alveolar surfactant layer isolates the outside from the inside of the body, our immune system has a class of specialized phagocytes, called macrophages. These macrophages penetrate the alveolar surfactant layer and can phagocytize the particles and microorganisms contained in the inhaled air, so as to maintain the cleanliness of the alveoli.
“Therefore, once COVID-19 enters the alveoli, alveolar macrophages wrap the virus particles on their surface cell membrane and swallow them into the cytoplasm, which encapsulate the vesicles of the virus, which are called endosomes.” Huang Bo said, “ endosomes can deliver virus particles to lysosomes, a waste disposal station in the cytoplasm, so as to decompose the virus into amino acids and nucleotides for cell reuse.”
However, COVID-19 can use the specific state of alveolar macrophages to escape from the endosomes, and in turn use macrophages to self duplication.
“Clinically, bisphosphonates such as alendronate (AlN) are used in the treatment of osteoporosis by targeting macrophages; the glucocorticoid drug as dexamethasone (DEX) is a commonly used anti-inflammatory drug.” Huang Bo said that we found that DEX and AlN can synergistically block the escape of virus from endocytosomes by targeting the expression of CTSL and the pH value of endosomes respectively.
As systemic administration is difficult to produce due to obstruction of the surface active layer of alveoli, Huang Bo said that the effect of such a combination therapy is achieved through nasal spray partly. At the same time, this combination can also play the role of hormone anti-inflammatory. This spray therapy is simple, safe, inexpensive and easy to promote. It is a new strategy for early control of COVID-19 infection.