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Coronavirus fusion peptide plays more invasive role in infection than previously thought

Although the COVID-19 pandemic was the first time most of humanity learned of the now infamous disease, the family of coronaviruses was first identified in the mid-1960s. In a new study, molecular biologist Steven Van Doren, a scientist in the University of Mi

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Although the COVID-19 pandemic was the first time most of humanity learned of the now infamous disease, the family of coronaviruses was first identified in the mid-1960s. In a new study, molecular biologist Steven Van Doren, a scientist in the University of Missouri College of Agriculture, Food and Natural Resources, has uncovered unexpected actions of a key player in how the coronavirus infects its target - a discovery that could guide further vaccine development.

Funded by a National Science Foundation (NSF) grant, Van Doren and his team studied the fusion peptide, an important feature of the spike protein that serves to bind the virus with the human cell, an essential step in the course of infection. In this study, they found that the fusion peptide plays a more invasive role in fusing the virus to the cell than previously thought, which is significant in understanding how infection occurs.

The fusion peptide is the most preserved part of the whole viral spike. Throughout the evolution of this virus, the fusion peptide endured despite all the mutations and variants that we kept on hearing about in the news. The fusion peptide never changed much and stayed a constant feature on the virus spike because it's too critically important for infection for it to be modified." Van Doren, professor of biochemistry

The fusion peptide on the SARS-CoV-2 spike (pictured here) plays a key role in virus/cell attachment.

This research is interesting to compare to a recent study that surveyed asymptomatic patients who were infected by the coronavirus because they had developed a defense mechanism known as broadly neutralizing antibodies. Van Doren's research on the functionality of the fusion peptide's ability to puncture a cell membrane could further inform why the fusion peptide may be an important target for vaccine development capable of fighting all types of coronavirus infections.

Another potential application of this research could be to create a novel strategy to penetrate cells.

"There may be many strategies for crossing membranes, but it's conceivable that the fusion peptide work could help further development of more ways to cross cellular membranes, which could be useful to deliver therapeutics through cell membranes," Van Doren said.

Further, this research broadens understanding of protein insertion in membranes, which has broader relevance to the scientific community.

"I love what protein molecules look like and what they can do," Van Doren said. "I got fascinated by the science when I was still a teenager, and it's intriguing to me the things they can do, so studying how proteins work has been something that has stuck with me for decades now - I'd say going on almost 40 years."

The study "SARS-CoV-2 Fusion Peptide Sculpting of a Membrane with Insertion of Charged and Polar Groups" was published in Structure. Co-investigators include Benjamin S. Scott and Rama K. Koppisetti.

Van Doren, S.R., et al. (2023) SARS-CoV-2 fusion peptide sculpting of a membrane with insertion of charged and polar groups. Structure. doi.org/10.1016/j.str.2023.07.015.

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Related questions

01How does vitamin D strengthen the immune system?

More specifically, the study showed that the female patient produced very few cathelicidins, which is a natural toxin found in the immune cells of the lungs needed to fight tuberculosis. In most people infected by tuberculosis, tuberculosis bacteria attack the immune cells of the lungs. The immune cells fight the bacteria by eating them. But the tuberculosis bacterium has developed various evasive mechanisms that reduce the immune cells’ ability to digest and thus to kill the Mtb. “You could say that the tuberculosis bacterium has developed a way to lull the immune cells to sleep. This enables the disease the hide inside the immune cells, making it invisible to other parts of the immune system,” Martin Kongsbak-Wismann explains. This is where vitamin D enters the picture. Because vitamin D is able to counteract the soporific effect of the tuberculosis bacteria by making the immune cells produce more of the cathelicidin toxin. “Cathelicidin is like a microscopic needle that is able to pierce the tuberculosis bacteria. And when it does, it weakens the bacteria’s soporific effect on the immune cells. This restores the immune cells’ ability to kill tuberculosis bacteria,” says Martin Kongsbak-Wismann and adds: “We were amazed by the effect of vitamin D. In immune cells from healthy control subjects, vitamin D improved the cells’ ability to fight Mtb, whereas in the female patient’s immune cells we saw no response to vitamin D. This shows that vitamin D is key to the immune system’s ability to fight Mtb and prevent tuberculosis.” Al-Jaberi, F.A.H., et al. (2022) Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report. Frontiers in Immunology. doi.org/10.3389/fimmu.2022.1038960.

Source: www.news-medical.net ↗
02What is the relationship between the pH and pKa of an amino acid?

The pKa for an amino acid is an acid dissociation constant that refers to the equilibrium between the protonated and deprotonated forms of the backbone amino group, backbone carboxyl group, and any potential acid/base component of the variable group. The net charge of the protein is determined by summing the charge of individual amino acids across the protein. pKa relates to the equilibrium constant and defines the transition between two structural forms of an amino acid–protonated and deprotonated. Amino acids possess distinct pKas for the carbonyl group, amino group, and any functional groups on the side chain that may be protonated or deprotonated. There is always one more structure than the number of pKa values for amino acids. For example, if there were two pKa values, three structures can be discerned. This is illustrated below using glycine, which has two pKa values – pKa 1 represents the (de)protonation of the carboxyl group and pKa2 represents the (de)protonation of the amine group: When the pH< pKa protonation of the amino and carboxyl groups occurs, resulting in a net +1 positive charge for glycine. When the pH is increased to a value between the two pKas(pKa2>pH> pKa1), the carboxyl group is deprotonated while the amino group remains protonated. This represents the zwitterionic form of the amino acid as it simultaneously possesses a positive and negative charge. When the pH> pKa2, the amino group is deprotonated and loses its charge. The amino acid now carries a net negative charge of -1. The zwitterionic form of the amino acid can exist at any pH value between pKa1 and pKa2.

Source: www.news-medical.net ↗
03What is CAR structure?

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Source: www.news-medical.net ↗
04What are BCAAs?

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Source: www.news-medical.net ↗
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Source: www.news-medical.net ↗
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