In silico analysis of 14 ACE2 single-nucleotide polymorphisms revealed that 7 SNPs altered protein binding capabilities, suggesting these variants may affect COVID-19 susceptibility.
In silico analysis suggests that specific ACE2 gene polymorphisms may alter mRNA structure and protein binding, potentially influencing COVID-19 susceptibility.
BACKGROUND: Novel coronavirus (SARS-CoV-2) became an epidemic disease and lead to a pneumonia outbreak first in December 2019 in Wuhan, China. The symptoms related to coronavirus disease-19 (COVID-19) were different ranging from mild to severe lung injury and multi-organ failure symptoms, eventually leading to death, especially in older patients with other co-morbidities. The receptor of this virus in the human cell is angiotensin-converting enzyme 2 (ACE2). METHODS: In this paper, we aimed to perform an in silico analysis of the frequently studied variants of the ACE2 gene and determine the effects of the variants in mRNA secondary structure and binding affinity of cellular factors. Fourteen single-nucleotide polymorphisms were selected based on previous studies and investigated. RESULTS: All of the variants were analyzed in the RNAsnp database and three revealed a significant p-value. The spliceAid2 database prediction showed that 7 out of 14 SNPs caused an alteration in a way that only the wild or mutated form was able to bind to proteins. The latter database also reported that three SNPs produces a dual form in which different specific proteins can bind to the sequence in a specific form (either wild or mutated form). CONCLUSION: Altogether, these estimations revealed the potential of variants in manipulation of the final stable form of ACE2 that can lead to different COVID-19 susceptibility.
Pouladi et al. (Mon,) conducted a other in COVID-19 susceptibility. ACE2 gene polymorphisms vs. Wild-type ACE2 sequence was evaluated on Alteration in mRNA secondary structure and binding affinity of cellular factors. In silico analysis of 14 ACE2 single-nucleotide polymorphisms revealed that 7 SNPs altered protein binding capabilities, suggesting these variants may affect COVID-19 susceptibility.