COVID-19 susceptibility: potential of ACE2 polymorphisms

Chaudhary, Mayank

doi:10.1186/s43042-020-00099-9

Cited by 29 publications

(27 citation statements)

References 57 publications

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“…Notably, ACE2 level of expression, which differs among people, could correlate with susceptibility to the infection ( Devaux et al, 2020 ). Polymorphisms of regulatory and non-coding regions such as promoters or 3’-UTR in ACE2 can have a role in the different expression levels of ACE2 among individuals ( Chaudhary, 2020 ; Lippi et al, 2020b ). Association between some mutation of ACE2 (affecting its expression) with the SARS-CoV intake was also strengthened the possible effect of ACE2 variant on SARS-CoV-2 entrance ( Lippi et al, 2020a ).…”

Section: The Role Of Ace2 Variants In Sars-cov-2 Infection and Severimentioning

confidence: 99%

Variants in ACE2; potential influences on virus infection and COVID-19 severity

Bakhshandeh

Sorboni

Javanmard

et al. 2021

Infection, Genetics and Evolution

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The third pandemic of coronavirus infection, called COVID-19 disease, was first detected in November 2019th. Various determinants of disease progression such as age, sex, virus mutations, comorbidity, lifestyle, host immune response, and genetic background variation have caused clinical variability of COVID-19. The causative agent of COVID-19 is an enveloped coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that invades host cells using an endocytic pathway. The SARS-CoV-2 spike protein is the main viral protein that contributes to the fusion of the virus particle to the host cell through angiotensin-converting enzyme 2 (ACE2). The highly conserved expression of ACE2 is found in various animals, which indicates its pivotal physiological function. The ACE2 has a crucial role in vascular, renal, and myocardial physiology. Genetic factors contributing to the outcome of SARS-CoV-2 infection are unknown; however, variants in the specific sites of ACE2 gene could be regarded as a main genetic risk factor for COVID-19. Given that ACE2 is the main site for virus landing on host cells, the effect of amino acid sequences of ACE2 on host susceptibility to COVID-19 seems reasonable. It would likely have a substantial role in the occurrence of a wide range of clinical symptoms. Several ACE2 variants can affect the protein stability, influencing the interaction between spike protein and ACE2 through imposing conformational changes while some other variants are known to cause a decrease or an increase in the ligand-receptor affinity. The other variations are located at the proteolytic cleavage site, which can influence virus infection; because soluble ACE2 can act as a decoy receptor for virus and decrease virus intake by cell surface ACE2. Notably, polymorphisms of regulatory and non-coding regions such as promoter in ACE2, can play crucial role in different expression levels of ACE2 among different individuals. Many studies should be performed to investigate the involvement of ACE2 polymorphism with susceptibility to COVID-19. Herein, we discuss some reported associations between variants of ACE2 and COVID-19 in details. In addition, the mode of action of ACE2 and its role in SARS-CoV-2 infection are highlighted which is followed by addressing the effects of several ACE2 variants on its protein stability, viral tropism or ligand-receptor affinity, secondary and tertiary structure or protein conformation, proteolytic cleavage site, and finally inter-individual clinical variability in COVID-19. The polymorphisms of regulatory regions of ACE2 and their effect on expression levels of ACE2 are also provided in this review. Such studies can improve the prediction of the affinity of mutant ACE2 variations with spike protein, and help the biopharmaceutical industry to design effective approaches for recombinant hACE2 therapy and vaccination of COVID-19 disease.

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Section: The Role Of Ace2 Variants In Sars-cov-2 Infection and Severimentioning

confidence: 99%

Variants in ACE2; potential influences on virus infection and COVID-19 severity

Bakhshandeh

Sorboni

Javanmard

et al. 2021

Infection, Genetics and Evolution

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“…Such response cytokine storm was showed in ACE2-positive cells. Thus, differences in response to COVID-19 associated with genetic polymorphism within the genes responsible for the synthesis of cytokines and pro-inflammatory mediators along with ACE2 [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic susceptibility of COVID-19: a systematic review of current evidence

et al. 2021

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Introduction While COVID-19 pandemic continues to spread worldwide, researchers have linked patterns of traits to poor disease outcomes. Risk factors for COVID-19 include asthma, elderly age, being pregnant, having any underlying diseases such as cardiovascular disease, diabetes, obesity, and experiencing lifelong systemic racism. Recently, connections to certain genes have also been found, although the susceptibility has not yet been established. We aimed to investigate the available evidence for the genetic susceptibility to COVID-19. Methods This study was a systematic review of current evidence to investigate the genetic susceptibility of COVID-19. By systematic search and utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct, we retrieved all the related papers and reports published in English from December 2019 to September 2020. Results According to the findings, COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. Previous studies have shown that people with ACE2 polymorphism who have type 2 transmembrane serine proteases (TMPRSS2) are at high risk of SARS-CoV-2 infection. Also, two studies have shown that males are more likely to become infected with SARS-CoV-2 than females. Besides, research has also shown that patients possessing HLA-B*15:03 genotype may become immune to the infection. Conclusion Combing through the genome, several genes related to immune system’s response were related to the severity and susceptibility to the COVID-19. In conclusion, a correlation was found between the ACE2 levels and the susceptibility to SARS-CoV-2 infection.

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“…Their study finds a moderate variation of ACE2 expression in different population [33] and remarkably, they revealed a positive correlation between the presence of higher allelic frequency and elevated tissue expression of ACE2 in East Asian population, but no ACE2 mutant was found to resist viral binding to host cell [33]. As various studies and reviews have not identified any specific relation between ACE2 SNP (Single Nucleotide Polymorphism) and severity of COVID 19 in various ethnic groups yet, so further screening is needed [34].…”

Section: Genetic Factorsmentioning

confidence: 94%

An Insight into ACE2 Expression Associated Complexities of COVID-19 and the Possible Vaccine Strategies to Control Viral Entry into Host Cells

Fariha¹,

Syfuddin²,

Ahmed³

2021

AJIM

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The first detected COVID-19 virus in China in late December 2019, has now spread to over 200 countries and territories across the globe. As it is a novel virus, in course of time, new symptoms and new complexities in patients have arisen, which demand immediate attention. This ambiguous, fast mutating nature and strain variations of SARS CoV2 have hindered the way of vaccine development. However, recognizing this new virus as a member of coronavidae family and its similarity with previously prevailed SARS-Cov virus has advantages in order for its further characterization and identification of the route of entry. Hence, this review aims at providing an overview of the viral entry pathway and explaining the reasons behind the vulnerability of an individual based on his/her age, sex, weight, other existing diseases and genetic make-up. It will also try to explicate various newly emerged symptoms of COVID-19 from the perspective of cytokinin storm theory. Furthermore, it summarizes all the therapeutic strategies based on preventing virus entry, some of which are already developed or under trial or yet confined in theory using currently published literature, scientific reports and research articles about SARS-CoV2. This review will help better understand the COVID-19 complicacies with latest concepts on therapeutic strategies against SARS-CoV2.

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COVID-19 susceptibility: potential of ACE2 polymorphisms

Cited by 29 publications

References 57 publications

Variants in ACE2; potential influences on virus infection and COVID-19 severity

Variants in ACE2; potential influences on virus infection and COVID-19 severity

Genetic susceptibility of COVID-19: a systematic review of current evidence

An Insight into ACE2 Expression Associated Complexities of COVID-19 and the Possible Vaccine Strategies to Control Viral Entry into Host Cells

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