The lack of a lung protective protein in the Caucasian population may have made Europe and North America more susceptible to the spread of a coronavirus variant compared to Asia. This is what a study by Indian scientists suggests, which also shows how mutant forms of the virus may find new ways to infect people.
The study, published in the journal Infection, Genetics and Evolution, looked at the global distribution of the coronavirus variant with the D614G mutation, the predominant lineage that infects North America and European populations.
This variant spread so quickly that in just 10 weeks between February and March 2020, over 64.11 percent of people infected worldwide were identified as carrying the mutated virus, starting with just 1.95 percent in January.
However, the researchers, including those at the National Institute for Biomedical Genomics (NIBMG) in Kalyani, West Bengal, said that it took this subtype significantly longer to reach a relative frequency of 50 percent – 5.5 months – compared to that in East Asia 2.15 months in Europe and the 2.83 months in North America.
According to the scientists, a deficiency of the alpha-anti-trypsin (AAT) protein in the populations of Europe and North America is one of the main factors that explain the rapid spread of this variant on the two continents compared to its transmission in Asia.
“In order for the coronavirus to enter cells, its spike protein binds to the ACE2 receptor in human cells, and the human enzyme TMPRSS2 cleaves at the junction of two subunits S1 and S2 of the protein, allowing the virus to fuse with the cell,” said he study corresponding author Nidhan K Biswas of NIBMG.
“Because of the D614G mutation in the spike protein, the virus received an additional cleavage site that enables it to fuse better with cells,” Biswas told PTI.
In lines of the coronavirus that carry the D614G mutation, the 614th molecule of the virus spike protein labeled D – aspartic acid – is replaced by the molecule labeled G, glycine.
“Instead of one cleavage site, the mutated virus has two such sites, and it can use this twice and enter cells more easily,” explained Biswas.
Based on the current study, he said this spot in the virus is cleaved by the host protein’s neutrophil elastase, which is normally involved in clearing bacterial infections in the lungs.
The levels of elastase molecules in the body are naturally kept under control by AAT, whose primary function is to protect the lungs from inflammation and tissue damage, according to the study.
“The problem is that when we have high neutrophil elastase, it also damages the lung cells more. So there is a balance mechanism via the AAT enzyme that is naturally present in every lung,” explained Biswas.
According to the study, AAT deficiency is widespread in European and North American populations, but much less common in East Asia.
According to Biswas, the AAT deficiency is very high in the general population in Italy and Spain.
He explained that the lack of this protein makes it much easier for the neutrophil elastase molecule to act on the virus spike subunits, resulting in a significantly faster spread of this mutant.
“The problem is that people who are AAT deficient have high levels of neutrophils. When infected with the SARS-CoV-2 virus with the D614G mutation, their cells can quickly take up the virus throughout the system,” the NIGMB explained -Scientist.
The researchers believe that this finding, along with other social factors, could explain the different geographic / ethnic distribution of 614G.
While the results provide evidence of the transmission of the virus variant, Biswas warned against any interpretations of the study about the severity of the disease and the mortality caused by the strain.
He said the research is also providing some evidence of the spread of other variants of the coronavirus, such as those first reported in the UK and South Africa, that are “built on the backbone of the D614G mutation.”
‘The British and South African variants also have this mutational backbone, so they may have a similar pattern of transferability and may have additional capabilities for scientists to figure out,’ added Biswas.
He said, however, that more experimental studies on cells cultured in the laboratory are needed to validate these conclusions.
The scientists believe that the results will open the possibility for consideration of AAT supplements in preventing infection with the SARS-CoV-2 virus subtype D614G.
(Except for the headline, this story was not edited by GossipMantri staff and published from a syndicated feed.)