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The SARS-COV-2 S-protein impacts cell survival via apoptosis, a programmed cell death pathway.

AJAS · 2022 Microbiology

Katherine Fang

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Overview

The current pandemic of novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) poses a severe global public health threat. Studying the molecular mechanisms of SARS-CoV-2 is critical to finding effective therapeutic strategies to battle this deadly disease. Previous studies have reported that SARS-CoV-encoded accessory proteins cleaved by cysteine protease played a role in inducing apoptosis, one of several types of programmed cell death. Clinically, gene expression levels of selected caspases were increased in in vitro SARS-CoV-2 infection models. Single cell RNA-Seq data of blood from COVID-19 patients showed distinct caspase expression in T-cells, neutrophils, and dendritic cells. Presently, the exact mechanisms of programmed cell death upon SARS-CoV-2 infection remain to be elucidated. This study first examines the impact of the SARS-CoV-2 spike protein on proliferation of lung/gut/brain cell lines using MTT assays. Next, LDH and caspase assays are used to investigate whether the S-protein can induce necrosis and/or apoptosis. T-tests and fold-change analyses are used to analyze the data. The experiments show insignificant necrosis for gut and brain cells, but significant elevated spike protein-induced apoptosis activities are present with caspase-9 and caapase-3. Caspase-3 experiments also show that caspase-3 inhibitors, curcumin and luteolin, display abilities to suppress caspase-3 apoptosis. These discoveries of apoptosis induction and inhibition may assist in the development of therapeutic strategies to treat COVID-19.

Video

My Story

I still remember having a successful regional band performance in March 2020 and then suddenly moving my life online due to COVID-19—and we haven’t returned back to our normal lives since. This pandemic was caused by a little virus called SARS-COV-2, and I was very intrigued to learn more about it. I read many papers to understand the structure of the virus and how it invades our cells. As much as I admired what scientists knew about this virus based on other coronaviruses, I was surprised at how confusing a lot of information was. I wished to learn more through my own, firsthand lab work! I was lucky that Dr. Zhu gave me the opportunity to carry out some experiments about a part of the virus known as the spike protein. I have learned about some brilliant biological processes that help us understand whether the S protein damages the cells and what process it uses to do that. These processes can be examined using well-designed experiments, and the measurements are taken by an instrument called a spectrophotometer. It’s great to be a member of the crew who worked together to combat the pandemic, and I’m very excited to share what I have found with you here!

Images (14)

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Awards (1)

  • AJAS Fellows Badge

Competition history

  • AJAS 2022 Microbiology

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Source: ProjectBoard / American Junior Academy of Science

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