Protein synthesis in COVID-19: Here’s how SARS-CoV-2 disrupts protein production in healthy cells
The study suggests that the Nsp1 protein-ribosome binding could be a possible target for drug therapies against the coronavirus.
In recent research, a group of scientists at the University of Munich have found that Nsp1, a protein present in the COVID-19 causing virus SARS-COV-2, takes over the protein production in cells and suppresses immunity, making the body unable to properly fight the infection.
Nsp1 is a non-structural protein, which means that the virus produces this protein inside the host cells, and it is not really a part of the viral structure. The findings of the study are published in the peer-reviewed journal Science.
Protein synthesis and viral diseases
Viruses are intracellular parasites. They need a living host to survive. Once inside a host cell, a virus uses the machinery of the host which is involved in protein production, to make multiple copies of itself which then leave the original cell and infect the surrounding cells.
This process of protein synthesis in the body is called translation. The mRNAs (messenger RNAs) in our body cells hold the code for the various proteins we need. The machinery needed for translation is present inside ribosomes, a small organelle present inside the cytoplasm (everything apart from the nucleus inside the cell). The ribosome has two parts - a small 40S subunit and a larger 60S subunit. The smaller subunit binds to the mRNA first and then the larger subunit binds to the whole.
Protein synthesis or translation occurs in three steps: initiation, elongation and termination.
Before the RNA binds to the 40S subunit, the latter binds with various proteins (initiation factors) to prepare itself for the translation process. The binding of the mRNA to the ribosome is very specific. Every mRNA has a special ‘cap’ on one end that determines from which end of the RNA molecule the protein production would begin (mRNA as a chain of nucleotides just like DNA). Nucleotides are a complex of sugars and bases. Once the ribosome scans and finds the beginning site of the protein synthesis, the 60S subunit binds and protein synthesis initiates.
In elongation, various amino acids are formed from the mRNA. Amino acids are the building blocks of proteins. Termination occurs once the desired protein is formed. A special code on the mRNA signals the termination process. Viruses interfere with the process of translation at various levels to stop protein synthesis in host cells.
The new study
Previous studies with the SARS virus have shown that Nsp1 binds with the 40S subunit and makes changes in the cap region of the mRNA, which stops protein synthesis in the host cell. Also, this protein cleaves the host mRNA, which completely stops protein synthesis in the host cell. However, the viral mRNA remains intact in this process. Nsp1 protein shows a similar function in all coronaviruses.
The shut down of protein synthesis also keeps the host cell from mounting an antiviral response through the production of type-1 interferons - in the absence of which, the virus thrives in the host body. Type-1 interferon is a protein that regulates the innate immune system - the immune system we are born with. However, Nsp1 does not affect all the types of immune cells even in the innate immune system.
Possible drug therapy
The study suggests that the Nsp1 protein-ribosome binding could be a possible target for drug therapies against the coronavirus. Since the binding site of the Nsp1 is not important for ribosome function, a drug masking this site and thus preventing the binding of the Nsp1 protein with the ribosome may be effective in reducing the damage caused by the SARS-CoV-2 virus.
Also, it may be helpful to understand how the virus protects its own RNA from being damaged when it cleaves the host RNA.
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