Title : Effects of the natural compound on SARS-CoV-2 spike protein-mediated metabolic alteration in THP-1 cells explored by the 1H-NMR-based metabolomics approach

Abstract:

A change in metabolism is one of the hallmarks of coronavirus disease 2019 (COVID-19) that cause severity and mortality. The mechanism of SARS-CoV-2 spike protein-mediated perturbations of metabolic pathways and modulation of antcin A, a steroid-like compound isolated from Taiwanofungus camphoratus, are not studied. Here, we investigated the metabolic alteration by SARS-CoV-2 spike protein and the regulatory effect of antcin A on SARS-CoV-2 spike protein-induced metabolic changes in the Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) cells using proton nuclear magnetic resonance (¹H-NMR) and MetaboAnalyst 5.0 software.

The cytotoxic potential of SARS-CoV2 spike protein, antcin A, and dexamethasone was assessed by MTT assay. The metabolomic perturbations and their relation to human coronaviruses' receptors were evaluated by qPCR. This study indicated that the altered metabolites mediated by SARS-CoV-2 protein, such as methionine, phosphoenolpyruvic acid, canadine, glutamine, ethanolamine, and phenylalanine, were significantly reversed by antcin A. In addition, antcin A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors, while GRP78 inhibition was not statistically significant.

This is the first study to use ¹H-NMR to investigate SARS-CoV-2 spike protein-induced metabolomic changes in PMA-induced THP-1 cells. Antcin A significantly reversed metabolomic alters while dexamethasone failed to fix them. Therefore, antcin A could be a potential candidate for therapeutic agents for viral infections related to a metabolic abnormality.

KEYWORDS; SARS-CoV-2-spike, ¹H-NMR, Metabolomics, antcin-A, Taiwanofungus camphoratus

Audience Take Away

1. This study displayed that 1H-NMR is not only solving structure molecules, but it can apply for 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.
3. Natural compounds have more potential to rescue from metabolomic alteration via virus infection.
4. Metabolomic correction is a novel therapeutic approach to tackle virus-mediated metabolomic alteration.

Biography:

Mr. Gyaltsen Dakpa earned a bachelor's degree in biotechnology from Panjab University (2016), India, and a Master of Science in Biotechnology from Jawaharlal Nehru University  (JNU) in 2018. He spent a year teaching at Garden Jangtse Monastic University, India, collaborating with Emory University, USA. He enrolled as a Ph.D. student at National Chung Hsing and Academia Sinica in 2019 through the Taiwan International graduate program (TIGP). Currently, He is 4^th of Ph.D. Candidate and working on the effects of natural compounds on the SARS-CoV-2 Spike protein-mediated metabolomic alteration at the cellular level. Recently his paper has been accepted in Phytotherapy research. He also published a review article in 2022 at Progress in Molecular Biology and Translational Science.