Comprehensive in silico identification of impacts of ACE2 SNPs on COVID-19 susceptibility in different populations

Paniri, Alireza; Hosseini, Mohammad Mehdi; Moballegh-Eslam, Mojtaba; Akhavan‐Niaki, Haleh

doi:10.1016/j.genrep.2020.100979

Cited by 30 publications

(23 citation statements)

References 32 publications

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“…Finally, the comparison of rs233574 frequency between different populations revealed that all populations, except for South Asian, have a more prevalent C allele. According to the ability of the rs233574 sequence to bind to the ETR‐3 splicing factor, in the presence of the T allele, and the fact that distribution of rs233574 in Asians is significantly different compared with other populations (Paniri et al, 2021), it can be concluded that COVID‐19 susceptibility may increase in South Asian population (WHO.int, 2020). In conclusion, regarding the results from two in silico servers, 3 out of 14 selected SNPs estimated to be able to alter the RNA secondary structure of ACE2 .…”

Section: Discussionmentioning

confidence: 99%

Investigating the ACE2 polymorphisms in COVID‐19 susceptibility: An in silico analysis

Pouladi

Abdolahi

2021

Molec Gen & Gen Med

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The severe acute respiratory syndrome coronavirus (SARS-CoV) was first emerged 17 years ago (Drosten et al., 2003). Later in December 2019 in Wuhan, China, a novel coronavirus (SARS-CoV-2) appeared and was found that it is able to infect humans (Gorbalenya et al., 2020) and lead to a pneumonia outbreak (Jiang et al., 2020). This virus causes coronavirus disease-19 (COVID-19) with mild to severe lung injury and multi-organ failure symptoms, eventually leading to death, especially in older patients with other comorbidities. However, genetic or environmental factors increasing the susceptibility to SARS-CoV-2 remained unclear.Angiotensin-converting enzyme 2 (ACE2; OMIM accession number = 300335) was identified as the functional SARS-CoV receptor in vitro and in vivo (Imai et al., 2005;

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Section: Discussionmentioning

confidence: 99%

Investigating the ACE2 polymorphisms in COVID‐19 susceptibility: An in silico analysis

Pouladi

Abdolahi

2021

Molec Gen & Gen Med

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“…The effect of ACE2 variants on SARS-CoV-2 entrance may influence individuals' susceptibility to COVID-19 and impact final clinical outcomes [142] . ACE2 SNPs might cause different responses to ACE2 blockers used in COVID-19 patients because they strongly influence the function and stability of the ACE2 protein [143] .…”

Section: Susceptibility Of People With Dm To Develop Severe Covid-19mentioning

confidence: 99%

The underlying mechanisms for severe COVID-19 progression in people with diabetes mellitus: a critical review

Figueroa-Pizano¹,

Campa-Mada²,

Carvajal-Millan³

et al. 2021

AIMSPH

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<abstract> <p>Diabetes mellitus (DM) has a high incidence of comorbidities among patients with severe coronavirus disease 2019 (COVID-19). The elevated prevalence of DM in the world population makes it a significant risk factor because diabetic individuals appear to be prone to clinical complications and have increased mortality rates. Here, we review the possible underlying mechanisms involved in DM that led to worse outcomes in COVID-19. The impacts of hyperglycemia side effects, secondary comorbidities, weakened innate and adaptive immunity, chronic inflammation, and poor nutritional status, commonly present in DM, are discussed. The role of the SARS-CoV-2 receptor and its polymorphic variations on higher binding affinity to facilitate viral uptake in people with DM were also considered. Clinical differences between individuals with type 1 DM and type 2 DM affected by COVID-19 and the potential diabetogenic effect of SARS-CoV-2 infection were addressed.</p> </abstract>

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“…The latter has been also shown in a study by Guo et al where different missense mutations were shown to affect ACE2 secondary structure and weaken its activity [79]. A recently published study that investigates the impact of ACE2 mutants on COVID-19 susceptibility shows that ACE2 SNPs could greatly influence its folding, its expression, and its interacting miRNA and consequently affecting the viral susceptibility [80]. Compared to ACE2, a point mutation on the 1069 residue of ACE, located in the C-terminal domain, is reported to be responsible for autosomal renal tubular dysgenesis (RTD) disease.…”

Section: Discussionmentioning

confidence: 62%

ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

Badawi

Ali

2021

Hum Genomics

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With the emergence of the novel coronavirus SARS-CoV-2 since December 2019, more than 65 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases, leading to over 1.5 million deaths globally. Despite the collaborative and concerted research efforts that have been made, no effective medication for COVID-19 (coronavirus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in the human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to tackle the virus through the use of angiotensin-converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2, which does not directly aim to reduce its membrane availability. However, through this review, we present a different perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, and shedding and cellular trafficking pathways including the internalization are not well elucidated in literature. Therefore, we hereby present an overview of the fate of newly synthesized ACE2, its post translational modifications, and what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Moreover, an extensive understanding of these processes is necessarily required to evaluate the potential use of ACE2 as a credible therapeutic target.

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Comprehensive in silico identification of impacts of ACE2 SNPs on COVID-19 susceptibility in different populations

Cited by 30 publications

References 32 publications

Investigating the ACE2 polymorphisms in COVID‐19 susceptibility: An in silico analysis

Investigating the ACE2 polymorphisms in COVID‐19 susceptibility: An in silico analysis

The underlying mechanisms for severe COVID-19 progression in people with diabetes mellitus: a critical review

ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

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