Studying viral proteins to identify potential targets for COVID-19 therapeutics

What is it about?

SARS-CoV-2, the virus causing the recent COVID-19 pandemic, continues to infect millions of people around the world. Till date, no drugs or vaccines exist to target this virus. As such, we need to look for viral targets that may be exploited to develop therapeutics against SARS-CoV-2. In structure, this virus resembles SARS-CoV-1, the causative agent of severe acute respiratory syndrome. The primary protease (Mpro) is an essential protein of SARS-CoV-2. Scientists suggest that inhibiting this protein could stop the virus from multiplying. The first step in this direction is to know more about the structure of the protein. Accordingly, in this study, researchers have compared the structure and composition of Mpro from SARS-CoV-1 and SARS-CoV-2. They found that the protein skeleton of SARS-CoV-2 Mpro is 1900% more sensitive than that of SARS-CoV-1 Mpro. Among the amino acids forming the backbone of SARS-CoV-2 Mpro, the cysteine at position 145 (Cys-145) is crucial for binding to Mpro inhibitors. This suggests the important role this singular amino acid may play in stopping SARS-CoV-2 from multiplying.

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Photo by CDC on Unsplash

Photo by CDC on Unsplash

Why is it important?

There are several ways to stop a virus from multiplying in a host. The most sought-after approach is to target and inhibit specific proteins of the virus. For this, such viral targets need to be first identified. Structural studies of viral proteins can help in this regard. The amino acids of SARS-CoV-2 Mpro are arranged in a network and interact with each other. Specific amino acids, like Cys-145, are sensitive to inhibitor drugs. They show altered response when exposed to these inhibitors. As such, these amino acids could act as suitable antiviral targets. KEY TAKEAWAY: Knowledge of the structure of SARS-CoV-2 Mpro can help us identify which parts of the virus body are the most sensitive. This can tell us how the virus will react to certain drugs or vaccines. By targeting its weak spots, we can make the virus less infective and reduce its transmission. This could help in controlling the COVID-19 pandemic.