Unprecedented research has shown how some proteins that form the surface of the coronavirus may be playing a key role in the high replication capacity of some of its variants.
The main protein involved in this function is non-structural 6 (NSP6), which, when mutated, ends up creating a better connection between structures involved in the multiplication process of Sars-CoV-2 and the host cell. Others involved are NSP3 and NSP4.
This more “refined” connection between the compartment containing the virus inside the cell and other cellular components also works by preventing the organism’s natural defense against the invader, so it guarantees greater replicative success.
Among the variants of concern (VOCs) that carry this mutation are alpha, gamma (which emerged in Manaus), lambda and the subvariant BA.2, of the omicron, which is already prevalent in Brazil.
The discovery was published in an article in the journal Nature, the most prestigious in the scientific world, on the 12th. The research is the result of a collaboration between scientists from the Instituto Oswaldo Cruz, at Fiocruz, in Rio de Janeiro, and the Instituto Telethon de Genética e Medicine (Tigem), in Naples, Italy.
To investigate the cellular mechanisms involved in the multiplication of the coronavirus within our body, the researchers sought to understand the relationship of NSP6 with structures present in all our cells that end up being sequestered for the process of synthesis of Sars-CoV-2.
Among them are the replicative double membrane vesicle, which is a kind of bag in which the virus will make the synthesis of its genetic material in the cell (protected from the cellular external environment), the endoplasmic reticulum, whose function is to produce various molecules such as lipids and proteins essential for cellular processes, and lipid corpuscles, which are lipid (fat) rich structures within cells.
Basically, NSP6 can act by organizing and creating more efficient communication channels between the replicative vesicle (where the viral genome is) and the two other structures.
“The virus, when it invades the cell, it uses the machinery present in the host cells to carry out its replication process, and the Sars-CoV-2 coronavirus, as well as other viruses, does this process in places that are the vesicles of As these vesicles need components to form, this is where the communication provided by NSP6 works, organizing this replicative process”, explains Patrícia Bozza, head of the Immunopharmacology Laboratory at the Oswaldo Cruz Institute and one of the authors of the study.
Furthermore, NSP6 manages to filter the passage of lipids from the endoplasmic reticulum to the cytoplasm, but prevents the passage of proteins that could recognize the invader and attack it inside the cell.
“This communication, therefore, is carried out in a way that favors the passage of lipids, which are necessary for replicative vesicles, but restricting some other proteins. This is one of the mechanisms that can act in this greater replication”, he said.
Also according to the researcher, the deletion of a final part of NSP6 (more specifically three amino acids, which are the units that form proteins), manages to offer a better arrangement, organizing the replicative organelles in clusters composed of 15 units. Without this deletion, the number of units per bunch dropped to three, in addition to having an irregular shape.
“The observation we made comparing the different variants that carry this mutation with the original form from Wuhan is that this mutation arose independently in the strains and was selected because it confers an advantage, or gain in function, for the virus,” he says.
The research developed by scientists is called basic, that is, it started from an investigation to understand the functioning of a certain process. However, Bozza explains that knowing such targets can help, in the future, to develop more effective therapies against Sars-CoV-2.
“The study sought to understand which are the important elements for the virus to establish and replicate in the cell, but this is also relevant to understand which targets act in replication both from the point of view of the virus and the host cell, being able to develop antivirals that act on these mechanisms”, he adds.
