Could SARS-CoV-2 accessory protein be responsible for some COVID-19 signals?

Some people with coronavirus 2019 (COVID-19) develop symptoms, but others do not. In high-risk populations, such as the elderly and those with underlying health problems, they may have more severe symptoms.

A new study by researchers at the Université de Lyon, France, noted that some symptoms of COVID-19 such as cardiac arrhythmias, loss of smell, gastrointestinal distress, and difficulty taking oxygen can be explained by intermittent potential release of ORF7b, which is a protein accessory. found in the true acute coronavirus 2 (SARS-CoV-2) respiratory syndrome, the virus that causes COVID-19.

The study, published in the pre-print journal medRxiv *, clarifies the possible causes of some COVID-19 symptoms. Early in the pandemic, the marked symptoms of COVID-19 include cough, fever, and shortness of breath. As the pandemic has progressed, more symptoms have emerged, such as loss of smell and taste, headache, intestinal issues, and abdominal pain.

Structure of SARS-CoV-2

SARS-CoV-2 contains a spike protein (S) that binds to the host cell’s angiotensin-converting enzyme receptor 2 (ACE2), which acts as the cell’s gateway to capture the cell.

Coronaviridae is infected with single-stranded RNA viruses that affect birds and mammals, including humans. Routine pandemic is one of the largest events in history, with more than 106.61 million people worldwide and causing 2.33 million deaths.

Coronavirus reproduction is enabled by many highly conserved viral proteins. The viruses also encode accessory genes, a group believed to play an important role in virus reproduction and pathogenesis.

SARS-CoV-2 contains accessory proteins, which are essential for viral reproduction and can trigger a host response to the virus, affecting pathogenicity and virulence.

The ORF7b is an accessory protein of SARS-CoV-2, showing more than 93 percent order homology with bat virus virus 7b. This protein is a putative viral accessory protein encoded on subgenomic RNA 7. Previous studies have shown that ORF7b is not only an accessory protein but a structural component of the SARS-CoV-2 virus.

The study

In the present study, the researchers used cell-free synthesized ORF7b and revealed that ORF7b accumulates into stable multimers. Also, the ORF7b series shows a transmembrane segment. Therefore, the team believes that this accessory protein has the ability to inhibit important cellular processes involving leucine-zipper formation.

Leucine zippers work by regulating heart rhythm through the proliferation of phospholambans in cardiomyocytes. Next, cell-cell epithelial adhesion is dependent on E-cadherins.

The team noted that the most common symptoms of SARS-CoV-2 disease, such as cardiac arrhythmias, loss of smell, intestinal problems, and impaired oxygen intake, can be explained by a possible intervention from ORF7b.

ORF7b has the ability to inhibit cellular activity. a) In the heart muscle, SERCA catalyzes Ca2 + transport across the membrane. PLN is a protector of SERCA, thereby regulating Ca2 + transport, and ultimately shortening of heart muscle and heart rhythm. PLN binds to SERCA as a monomer, that is formed in a way that is dependent on phosphorylation. ORF7b has the ability to interact, through its leucine zipper, with PLN monomers. b) Decorative neurons give cilia to the mucus. They are supported by sustentacular cells in the epithelium. Only these support cells can enter the virus. Cell-cell adhesion between the same type and different cell types is mediated by E-cadherin. For E-cadherin to be adhesive, it must shrink, penetrating through the leucine zipper transmembrane. ORF7b has the ability to interact with adhesion by interacting its leucine zipper with the one from the E-cadherin transmembrane domain. Cartoon of olfactory endothelium modified from (56).

The team said ORF7b creates robust multimers, which are stabilized with a leucine zipper. They believe that the strong relationship between the ORF7b and the leucine zipper causes the viral protein to interact with transmembrane leucine zipper proteins, making ORF7b a major suspect or culprit for interfere with cell functions commonly seen in SARS-CoV-2 disease.

More specifically, we suggest that ORF7b is suspected as a causative agent for cardiac arrhythmia and odor loss, and the promotion of potential molecular centers, ”the team concluded.

Drugs that act on ORF7b by controlling their own interactions with cell proteins can be an important tool or tool in the battle against COVID-19.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical / behavioral practice, or be treated as information established.