Although many vaccines have been put into use in the effort to combat the COVID-19 pandemic, our resistance to different virus variants is still low. An overlooked study may offer us an avenue to improve that situation.
A study by Taiwan China Medical University (which is in the democratic country of Taiwan) found that peimine, extracted from the herb Fritillaria, can block SARS-CoV-2, the virus that causes COVID-19, from infecting human cells through its spike protein. The extract shows a significant preventive effect and has the potential to be developed as a drug or health food. The research results were published in the Journal of Food Biochemistry in July, 2022.
Wang Weijan, assistant professor of the Department of Biotechnology of Taiwan China Medical University, who participated in the research, said that there are two ways that the COVID-19 coronavirus can infect the human body.
One is that the virus uses the spike protein on its surface to bind to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human cells to invade cells. Another occurs when the ability of the spike protein to bind the ACE-2 is weak. When that happens, two proteases (TMPRSS2 and furin) on the cell membrane will edit and modify the fragments above the spike protein to enhance the binding force of the spike protein to ACE2, thus allowing the virus to invade human cells.
Peimine Inhibits Multiple Variants of SARS-CoV-2 from Invading Cells
Wang Weijan said that the research team conducted individual cellular experiments on 126 single compounds contained in the natural compound drug library and found that peimine extracted from Fritillaria cirrhosa or Fritillaria thunbergii, sciadopitysin extracted from ginkgo biloba, and many other plants contain compounds that have inhibitory effects on the invasion of SARS-CoV-2. Vanillic acid from the vanilla plant was also found to have this effect.
Since the COVID-19 can infect different cells via different mechanisms, the team did further research and found that peimine exhibits multiple effects in preventing a variety of cells from being infected by SARS-CoV-2.
The results of the study found that peimine has the potential to bind to the spike protein and ACE2, and can thus act as a blocker between the spike protein and ACE2, preventing the two from combining. Then the virus can find no way to enter the cell.
Facing rapidly changing mutant viruses, the research team conducted research on different virus strains, specifically Alpha, Beta, Delta, Gamma, Omicron, and their variants BA.4 and BA.5. It was found that peimine can bind to the spike proteins of different variants of viruses, blocking their binding to ACE2, and inhibiting viral invasion.
Because of these results, Wang believes that peimine has a high potential to prevent viral infection for re-mutant viruses that may appear in the future.
In addition, although furin can promote viral infection, studies have found that peimine also has an inhibitory effect on furin, and it is believed that peimine is a potential antiviral drug or health food in the future.
Application of Fritillaria in TCM
Peimine is extracted from the Liliaceae family plant Fritillaria. The more well-known species of Fritillaria include Fritillaria cirrhosa and Fritillaria thunbergia. The bulb of Fritillaria is usually used as a component in traditional Chinese medicine (TCM). It has the functions of moistening the lung, resolving phlegm, and relieving cough, and has anti-inflammatory, anti-cancer, and anti-pulmonary fibrosis properties.
Fritillaria cirrhosa is also one of the ingredients in the traditional cough remedy known as chuanbei loquat paste.
Wang said that this study also used the decoction of Fritillaria cirrhosa and Fritillaria thunbergia, as well as the diluted chuanbei loquat paste for experiments. He found these remedies also inhibited the virus.
However, since chuanbei loquat paste also contains other ingredients of TCM, further research is needed to determine whether the efficacy comes from Fritillaria.
Wang added that compared with vaccines, which allow people to first generate antibodies inside the body to block the virus, the research team hopes to use these small molecule drugs to block the invasion of the virus so that people can use common medicinal materials to prevent the virus from infecting them in daily life.
With the threats posed by long COVID and the ability of the parasitic SARS-CoV-2 virus to quickly replicate in the body, Wang and others hope Fritillaria can be used to prevent more people from catching the virus. And for the infected, it also appears it can help uninfected cells better ward off the virus, thereby preventing the virus from spreading to other cells.
Wang Weijan hopes that in the future, Fritillaria can be used to prevent and treat the upper respiratory tract, where viruses are most likely to invade. One potential treatment would be nose sprays.
The experiments were conducted in human cell lines using pseudotyped lentiviral particles that contain the SARS-CoV-2 spike protein. Since these lab conditions are far from a perfect replication of an actual infection, Wang Weijan said that the effect of the treatments on a real infection should be observed first, and only with proof of success can it be further used in clinical trials.