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Covid Research: Why Delta Variant Of SARS-CoV-2 Spreads Easily And Infects People So Quickly

Delta's outstanding capacity to catalyse membrane fusion causes it to be transmitted much faster, US scientists have explained in a study published in Science journal.

New Delhi: The Delta variant of SARS-CoV-2 has wreaked havoc across the globe, and has been the dominant strain for several months now. The variant spreads easily and infects people quickly. In a new study, published in the Science journal, scientists from Boston Children's Hospital have explained the reason why the Delta variant is so contagious. 

Last year, Bing Chen, the lead author of the new study, showed how other SARS-CoV-2 variants (Alpha, Beta, G614) became more infectious than the original virus. Chen found that a genetic change caused the spike protein on the virus' surface to be stabilised, according to the study conducted last year.

Soon after the study, the Delta variant emerged, and became the most infectious variant known to date.

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What Makes Delta Variant More Infectious

The spike protein of the SARS-CoV-2 needs to attach itself to a receptor called ACE2 to infect host cells. After attaching itself to the receptor, the spike changes its shape, and folds in on itself. As a result, the virus's outer membrane fuses with the membrane of the cell, thus allowing the virus to gain entry.

A statement issued by Boston Children's Hospital said Chen and his colleagues used two kinds of cell-based assays to demonstrate that Delta's spike protein is very good at membrane fusion. The researchers created a simulated delta virus, which was observed to infect human cells more quickly and efficiently than the other five SARS-CoV-2 variants, the study states. When cells had low amounts of the ACE2 receptor, the Delta variant found it easier to infect the cells, according to the peer-reviewed study.

Chen explained that membrane fusion requires a lot of energy, and needs a catalyst, and that delta stood out in its ability to catalyse membrane fusion, mentions a statement by the Boston Children's Hospital. He added that Delta's outstanding capacity to catalyse membrane fusion causes it to be transmitted much faster. This is also the reason why the Delta variant can infect more cells and produce high viral loads in the body, he said.

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How Mutations Affect Spike Protein's Structure

The researchers also investigated the effect of mutations on the spike protein's structure. They used cryo-electron microscopy to image spike protein's from the Delta, Kappa, and Gamma variants, and compared them to spikes of G614, Alpha, and Beta variants.

The researchers observed that the immune system recognises some changes in two key parts of the spike protein. There were changes in the receptor-binding domain (RBD), which binds to the ACE2 receptor, and the N-terminal domain (NTD) (first part of the protein that exits the ribosome during protein biosynthesis) in all six variants. 

The ability of neutralising antibodies to bind to the spike and contain the virus decreases due to mutations in either domain, the study said.

Chen said in the statement the large change in the NTD is responsible for the resistance of the Delta variant to neutralising antibodies. However, the RBD change led to little change in antibody resistance, he added.

Suggesting a more targeted strategy for developing next-generation Covid-19 vaccines and treatments, Chen said vaccines must not target the NTD, because the virus can quickly mutate and change its structure. He said it might be most effective to target the RBD, and to focus the immune system on that critical domain, rather than the whole spike protein.

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