The three-dimensional atomic map of the major enzyme in the corona...

In order to better understand how the new corona virus behaves and how to inhibit its spread, scientists were able to obtain the three-dimensional map that reveals the position of each atom and atom in the enzyme molecule essential for replication of the SARS-CoV-2 virus.

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Researchers at the US Department of Energy’s Oak Ridge Laboratory have used the neutron scattering method to identify important information that could improve the effectiveness of drugs that inhibit the virus while blocking the virus’ self-replication mechanism. The new study’s findings have long been published. In the scientific journal Journal of Biological Chemistry.

The SARS-CoV-2 virus, the virus responsible for Covid-19 disease, contains long chains of proteins composed of about 1900 residues of amino acids. In order for the virus to multiply, these chains need to be broken down and cut into shorter sections by an enzyme called a major protease. The active protease enzyme is formed from two identical protein molecules held together by hydrogen bonds. The development of a drug that inhibits or blocks the activity of this enzyme will prevent the virus from replicating and spreading to other cells in the body. “This new information is exactly what is needed to design inhibitors with a higher level of selectivity, a fact that ensures that inhibitor molecules will bind very tightly to targets while breaking down the enzyme,” explains the lead author of the study, Andrey Kovalevsky.

Mapping the location of each hydrogen atom

Neutron beam experiments initially revealed that the site containing the amino acids where the protein chains are cut exists in a negatively charged active state and not in a neutral state, contrary to previous hypotheses. In the second step, the researchers mapped the location of each hydrogen atom at the same points that the inhibitors are supposed to bind to in the protease enzyme, and also measured the electrical charges of the amino acids present there. In the experiments it was also possible to map the entire network of hydrogen bonds between the protein molecules that hold together the enzyme that allows to initiate the chemical process of cutting the protein chains. “Half of the atoms in each protein are mostly hydrogen atoms. These atoms are major players in the activity of the enzyme and are essential for the way drugs bind to enzymes,” the researcher explains. “If we do not know the locations of these hydrogens and how the electric charge is dispersed within the protein, we will not be able to effectively design inhibitors for that enzyme.”

The neutron study of the research team is based on a previous study published in the scientific journalNature Communications, While creating a complete atomic structure of the protease enzyme. The researchers also allowed the data obtained to be available (the data available) to the general public and the scientific community even before the publication of the two articles, in order to accelerate the development of solutions to the global epidemic.

Neutrons are an effective means of examining biological structures because they are not destructive and are particularly sensitive to light elements such as hydrogen atoms. “This may be the fastest protein structure ever obtained using a neutron scattering method. We started our neutron experiments in May, and within five months we were able to get the final structure and publish it. Usually such results are obtained within a few years rather than within a few months.” Now, the research team, and other researchers around the world in the field, will be able to use the newly obtained information to investigate the linking properties between molecules that are candidates for drugs in order to develop improved healing methods in the fight against the Cubid-19 virus.

Abstract Article Knowledge of the study

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