Covid-19 is affecting everyone around the globe. Read this article to find out how inhibitors enter our bodies!
Figure 1: An artists depiction of the COVID-19 virus
Introduction
Covid-19 has been the biggest health crisis in our world for the past three years. We have dealt with widespread cases, hospitalizations, and deaths because of it. In response to the Covid-19 threat, we have developed vaccines; however, vaccines may not be as effective in the elderly and those with a weakened immune system. One way to prevent Covid-19 in those for whom the vaccine is not as successful is to target the entryway process of Covid-19, or the method by which the virus enters into the cells.
How does COVID-19 Enter the Body?
The entryway process of Covid-19, also known as Sars-CoV-2, starts with the virus’s Spike protein. The Spike protein (S protein) is required for Sars-CoV-2 to enter a cell. The Spike protein can be broken up into two subunits (a smaller part of the S protein): S1 and S2. In the entry process, the S1 protein will bind to a receptor of the cell the virus wants to enter. Then, the S2 protein will be broken down by a protein in the cell. The breaking down of the S2 protein will allow the cell and the virus to fuse faster, which then allows Sars-CoV-2 to get into the cell.
Figure 2: shown in purple, the S1 protein of Covid-19 binding to a receptor in the cell. Shown in green, the S2 protein of Covid-19 breaks down (being cleaved), allowing the cell and the virus to fuse together.
Researchers want to target the entryway process described and specifically stop either the S1 protein from binding to a receptor in the cell or stop the S2 protein from breaking down. By stopping either of these two processes, Covid-19 will not be able to enter the cells and the virus will not infect our bodies. The research paper “Identification of potent small molecule inhibitors of SARS-CoV-2 entry," published online on October 2021, discovers a small molecule that blocks the S2 protein from breaking down, or being cleaved.
In the paper, the researchers decided to use High Throughput Screening to find an established small molecule drug (small molecule being a compound with a low molecular weight) that would block the S2 protein from being cleaved. High Throughput Screening is used to automatically test large amounts of compounds to see their effect on a biological target. In this case, the researchers tested 2,000 drugs to see how they would inhibit the S2 protein in cells in a controlled laboratory environment. The researchers also tested for the toxicity of the cells, meaning how much of the compound is needed to decrease the healthy cells in the sample.
From this process, the researchers were able to identify the small molecule “calpeptin” as an inhibitor of the Covid-19 entryway process. Calpeptin stops the S2 protein of the virus from being cleaved, or breaking down, which will then stop the virus and the cell from fusing together, which will then stop the virus from ever entering the cell.
Finding small molecules to inhibit the Covid-19 entry process is an important field as it offers another method of blocking the Covid-19 virus. Effective small molecules will allow us to fully inhibit the virus from ever entering our cells and entirely stop the virus’s negative consequences on our bodies. Researchers are continuing to develop and test small molecules in search of the most effective and least toxic drug to block the Covid-19 entry process into cells. Future plans in this research also include trying to discover what part of the S2 protein cleavage process these small molecules are inhibiting. As of right now, the specific part of this process the drugs are stopping is unknown. Discovering what exact part the small molecules are inhibiting in the breakage process would open up many new and exciting paths to identify even more small molecules that inhibit Covid-19 from entering our cells.
Citations:
“Identification of potent small molecule inhibitors of SARS-CoV-2 entry" research paper: https://doi.org/10.1016/j.slasd.2021.10.012
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