Dental Tribune India

Two proteins can explain why East Asian countries suffered significantly less compared to EU & US

By Rajeev Chitguppi, Dental Tribune South Asia
February 09, 2021

While several European and western countries are still struggling with Covid-19 cases, enforcing restrictions on social gatherings, life seems to have returned almost to normal in much of Asia, including India. There has been a surge in the reports trying to explain the low numbers in Asia, but almost all of them lack a biological mechanism behind the fall in numbers. Now, a team of Indian scientists has described a plausible mechanism responsible for the contrast in the numbers seen worldwide.

Asia has been witnessing a steady decline in the number of cases, while the opposite happening in the western world. Many analysts have tried to explain The mystery behind India's declining Covid cases - not only Indian media but even the western media trying to find an answer for a dramatic drop in Covid-19 cases in India.

While everyone is speculating on the drastic variation seen between the eastern vs western world, a team of Indian scientists from the National Institute of Biomedical Genomics in Kalyani, West Bengal, seems to have identified the deficiency of a particular human protein as the main reason behind the slow spread of mutant SARS-CoV-2 in Asia compared to the West.

The biological mechanism seems to be as follows:

  1. Mutation D614G: The novel coronavirus evolved to 10 additional subtypes within three months of being reported first in China. Two of the ten evolved subtypes (A2 and A2a) carried a mutation (D614G) in the spike protein -resulting in two subtypes 614d and 614G.
  2.  614G  > spread > 614D: In July 2020, an analysis of over 70,000 SARS-CoV-2 coronaviruses worldwide, revealed that the mutant subtype (614G) had outcompeted the pre-existing type (614D), which happened significantly faster in Europe and North-America than in East Asia.
  3. Cleavage site and neutrophil elastase: The D614G mutation introduced an additional cleavage site on the Spike protein of the virus, which enabled the virus to gain faster entry into the cells - but only after opening the new cleavage site - a function easily performed by neutrophil elastase, an enzyme abundantly available in the lungs.

    Hence, D614G mutation opens up a larger number of cells in individuals with high levels of neutrophil elastase, thus allowing more cells to be infected. This would, in turn, help the mutant spread faster from one infected individual to another.

  4. Alpha1-antitrypsin (AAT): A protein called alpha1-antitrypsin (AAT) keeps the neutrophil elastase levels under check, otherwise higher levels can damage the lung tissue. In other words, AAT inhibits neutrophil elastase production. However, some naturally-occurring mutations in the AAT-producing gene can cause  AAT deficiency, which leads to a rise in the neutrophil elastase levels. Thus, indirectly, AAT deficiency leads to an enhanced ability of SARS-CoV-2 to infect human cells and spread among people.
  5. Global variation: A large proportion of Caucasians in European countries and North America suffer from AAT deficiency due to the natural mutations seen in their populations - a mutation not so prevalent in Asian countries. This is the reason why 614G variant spread so widely in Europe and North America but not in Asia.
  6. Numbers in different countries: Portugal has the highest (almost 75 out of 1,000 individuals) AAT deficiency. Spain has the second-highest AAT deficiency (67.3/ 1,000). France has 51.9/ 1,000, Canada has 32.1/ 1000, and Canada has 29 per 1,000 individuals with AAT deficiency. Poland has the least AAT deficiency with 18.7 per 1,000 individuals.

    Among the East Asian countries, by contrast, Thailand has the highest (Almost 20/ 1,000) ATT deficiency, while and Malaysia and South Korea have 8 and 5.4 per 1,000 individuals respectively. Singapore has just 2.5 per 1,000 individuals.

Read the study here: SARS-CoV-2 mutation 614G creates an elastase cleavage site enhancing its spread in high AAT-deficient regions

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