What is it about?

COVID-19 is among the top 10 worst and deadliest pandemics in human history. It has killed over 6 million, equivalent to Tibet’s population, and infected over 600 million, including me. One of the leading causes of death in COVID-19 patients is the production of cytokines through hyper-inflammation-based interaction between host cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein as the spike (S) protein which plays a vital role in the receptor recognition and cell membrane fusion process for the infection and inflammation. Recently, some studies have shown metabolomic alteration could be another one of the hallmarks of (COVID-19) that cause severity and mortality. However, the mechanism of SARS-CoV-2 spike protein-mediated perturbations of metabolic pathways is still not fully understood. We have used nuclear magnetic resonance (NMR), which is generally used to detect tumor metabolism by taking blood and urine samples from hospital patients. We applied NMR to understand the metabolomic alteration mediated by the SARS-CoV-2 spike protein in the cells. It revealed that metabolomic pathways such as glycolysis, glutamine metabolism and fatty acid metabolism were changed due to spike protein infection in the cells. This is the first study that uses 1H-NMR to show the alteration of the cellular metabolic pathway by the spike protein. Besides, understanding the mechanism is enough to eradicate this infectious disease. We have used herbal medicine like antcin, which has been used for thousands of years as a folk remedy for various human illnesses. Herbal medicine has been playing in disease prevention and treatment. We investigated the effect of the antcin-A on the altered metabolomic pathway by spike protein using NMR as a technology. It is isolated from the fruiting bodies o Taiwanofungus camphoratus, which mainly grow in a different range of mountains in Taiwan. We found that the most altered metabolites mediated by the spike protein were significantly reversed by antcin A. In contrast, dexamethasone has failed to do it even though it has been used to treat COVID-19. Thus, natural compounds like antcin A could be potential candidates for therapeutic agents for viral infections related to metabolic abnormalities such as COVID-19.

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Why is it important?

Importance of our finding 1) This study displayed that 1H-NMR not only solves structure molecules and detects blood or urine sample metabolism but can also apply to diagnosis based on metabolomic biomarkers. 2) Only the SARS-CoV-2 spike altered the metabolomic pathway at the cellular level. Thus, the regulation of metabolic pathways is another clinical therapeutic strategy. Natural compounds have more potential to rescue from metabolomic alteration via virus infection. 3) Metabolomic correction is a novel therapeutic approach to tackle virus-mediated metabolomic alteration.

Perspectives

It is so jubilant to see our work in the international journal and make a small contribution to the method to solve the current global pandemic. Everyone is responsible for eradicating this infection because ང་ཚོའི་བོད་ཀྱི་གཏམ་དཔེ་ལ། ཆུ་ཐིགས་བསགས་པའི་རྒྱ་མཚོ། We Tibetan say that little drops of water make the mighty ocean. Vaccination is not the only solution to eradicate this infectious disease because the global vaccination effort could be under control. However, it might predict that the susceptible individuals and waning immunity after infection or vaccination changes in the virus through an antigenic drift that diminishes protection and re-entries from the zoonotic reservoir, and new viral infection disease may occur. More importantly, this pandemic shows initiatives in individual countries and the interdependence of the world to fight against new emerging diseases. For instance, Structural biologists solve the virus's structure, and geneticists understand the sequence of the virus's genome. We used NMR to understand and contribute to a better understanding of the virus and a new approach to treating the COVID-19 infection in metabolomic alteration. We hope you will enjoy reading this discovery and share it with your colleagues and friends to make the world healthier.

Mr Gyaltsen Dakpa
Academia Sinica

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This page is a summary of: Antcin A, a phytosterol regulates SARS‐CoV ‐2 spike protein‐mediated metabolic alteration in THP ‐1 cells explored by the 1 H..., Phytotherapy Research, November 2022, Wiley,
DOI: 10.1002/ptr.7670.
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