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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313315

ABSTRACT

Coronavirus disease (COVID-19), caused by SARS-CoV-2, has a higher case fatality rate (CFR) in European ethnic groups than in others, especially East Asians. One explanation to this phenomenon might be TMPRSS2, a key processing enzyme essential for viral infection. Here, we analyzed the allele frequencies of two nonsynonymous variants rs12329760 (V197M) and rs75603675 (G8V) in the TMPRSS2 gene using over 200,000 present-day and ancient genomic samples. We found a significant association between the CFR of COVID-19 and the allele frequencies of the two variants. Interestingly, they had opposing effects on the CFR: inverse correlation by V197, proportional correlation by G8V. East Asians have higher V197M and lower G8V allele frequencies than Europeans, possibly endowing resistance against SARS-CoV-2. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly affecting its ACE2 and viral spike protein processing negatively, ultimately resulting in reduced SARS-CoV-2 infection efficiency and CFR in East Asian ethnic groups.

2.
Mol Cells ; 44(9): 680-687, 2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1444539

ABSTRACT

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing.


Subject(s)
COVID-19/genetics , COVID-19/mortality , Serine Endopeptidases/genetics , COVID-19/ethnology , Gene Frequency , Humans , Models, Molecular , Mortality , Polymorphism, Single Nucleotide , Republic of Korea , Serine Endopeptidases/chemistry
3.
Sci Total Environ ; 767: 145413, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1071914

ABSTRACT

Bats are the likely zoonotic origin of several coronaviruses (CoVs) that infect humans, including SARS-CoV-1 and SARS-CoV-2, both of which have caused large-scale epidemics. The number of CoVs present in an area is strongly correlated with local bat species richness, which in turn is affected by climatic conditions that drive the geographical distributions of species. Here we show that the southern Chinese Yunnan province and neighbouring regions in Myanmar and Laos form a global hotspot of climate change-driven increase in bat richness. This region coincides with the likely spatial origin of bat-borne ancestors of SARS-CoV-1 and SARS-CoV-2. Accounting for an estimated increase in the order of 100 bat-borne CoVs across the region, climate change may have played a key role in the evolution or transmission of the two SARS CoVs.


Subject(s)
COVID-19 , Chiroptera , Animals , China/epidemiology , Climate Change , Evolution, Molecular , Genome, Viral , Humans , Laos , Myanmar , Phylogeny , SARS-CoV-2
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