New Delhi:
Deficiency of a lung-guarding protein in the Caucasian population may possibly have created Europe and North America more susceptible to the spread of a coronavirus variant as compared to Asia, suggests a study by Indian scientists which also reveals how mutant types of the virus may possibly locate new approaches to infect individuals.
The study, published in the journal Infection, Genetics and Evolution, assessed the international spread of the coronavirus variant with the D614G mutation, which is the predominant lineage infecting North America and European populations.
This variant spread so quickly that in just 10 weeks among February and March 2020 more than 64.11 per cent of globally infected people have been identified to carry the mutant virus beginning from only 1.95 per cent in January.
However, the researchers, such as these from the National Institute of Biomedical Genomics (NIBMG) in Kalyani, West Bengal, stated this subtype took a considerably longer time to attain a 50 per cent relative frequency in East Asia — 5.5 months — compared to the 2.15 months it took in Europe, and the 2.83 months it took in North-America.
According to the scientists, a deficiency of the protein Alpha-anti-trypsin (AAT) across the populations of Europe and North-America is one of the major variables that clarify the speedy spread of this variant in the two continents compared to its transmission in Asia.
“For the coronavirus to enter cells, its spike protein binds with the ACE2 receptor in human cells, and the human enzyme TMPRSS2 cleaves at the junction of two subunits S1 and S2 of the protein, enabling the virus to fuse with the cell,” stated study corresponding author Nidhan K Biswas from NIBMG.
“But due to the D614G mutation in the spike protein, the virus gained an additional cleavage site which enables it to fuse better with cells,” Biswas told PTI.
In lineages of the coronavirus carrying the D614G mutation, the 614th molecule of the virus spike protein — aspartic acid — denoted by D is replaced by the molecule glycine, noted as G.
“Instead of one cleavage site, the mutated virus has two such sites, and it can take dual advantage of this and enter cells more easily,” Biswas explained.
Based on the existing study, he stated this web-site in the virus is cleaved by the host protein neutrophil elastase which is generally involved in clearing up bacterial infections in the lungs.
The levels of the elastase molecules in the body are naturally kept in verify by AAT whose major function is to defend the lungs from inflammation and tissue harm, the study noted.
“The issue is that if we have high neutrophil elastase then it also creates more damage to the lung cells. So there is a balance mechanism via the AAT enzyme that already exists by nature in everyone’s lungs,” Biswas explained.
According to the study, AAT deficiency is extremely prevalent in European and North-American populations, but considerably significantly less in East Asia.
Specifically, Biswas stated AAT deficiency in the common population is incredibly higher in Italy and Spain.
He explained that the lack of this protein tends to make it considerably less difficult for the neutrophil elastase molecule to act on the virus spike subunits, resulting in a considerably more quickly spread of this mutant.
“The issue is that individuals with AAT deficiencies have high neutrophil levels and if they are infected with the SARS-CoV-2 virus with the D614G mutation, their cells can quickly take the virus up and into the whole system,” the NIGMB scientist explained.
The researchers think this discovering, along with other social variables may possibly clarify the differential geographical/ethnic spread of 614G.
While the findings supply clues about the transmission of the virus variant, Biswas cautioned against any interpretations of the study on illness severity and mortality triggered by the strain.
He stated the analysis also supplies some clues on the spread of other variants of the coronavirus such as the ones very first reported in the UK and South Africa which are “built on the backbone of the D614G mutation.”
“The UK and South African variants also have this mutation backbone so they may have a similar transmissibility pattern, and probably they may have additional capabilities that scientists need to find out,” Biswas added.
However, he stated additional experimental research on lab-cultured cells are required to validate these conclusions.
The scientists think the findings open up the possibility for considerations of AAT supplements in the prevention of infection with the D614G subtype SARS-CoV-2 virus.
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