key: cord-0979031-xirt6efg
authors: Abouelhoda, M.; Zekri, A.-R. N.; Hafez, M. M.
title: SARS-CoV-2 receptor mutation in Egyptian population
date: 2020-05-02
journal: nan
DOI: 10.1101/2020.04.27.20082206
sha: 5b5450c5d68119b32e494ef2c7a681d081c2ac6b
doc_id: 979031
cord_uid: xirt6efg

The Coronavirus disease 2019 (COVID-19) is a respiratory tract infectious disease caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 triggers severe pneumonia leading to acute respiratory distress syndrome and death in severe cases. According to WHO reported, Egypt is among the countries with low confirmed SARS CoV2 infected symptomatic cases and death. We postulate that one of the reasons for this may be due mutations in the viral receptor. Therefore this study was conducted to confirm or reject this postulation.

bioinformatics analyses were done. The ACE2 and BACE2 Alp 56 sequences were analyzed using bioinformatics software to detect the difference mutations among Egyptian population in comparison to international population databases. Our data concluded that no SNPs or mutations were detected in ACE2 or BACE2 Alp 56 receptor among Egyptian population, hence no correlation with the low symptomatic incidence/death of SARS-Cov-2 viruses in the Egyptian populations.

The SARS-CoV-2 causes a new type of pneumonia that forms a global public health problem. As of April 21, 2020, more than 2,300,000 confirmed COVID-19 cases were reported worldwide with 162 956 confirmed deaths. Angiotensin-converting enzyme 2 (ACE2) and Beta-site amyloid beta A4 precursor protein-cleaving enzyme 2 (BACE2 Alp 56) have been identified as the main receptor for SARS-CoV-2. ACE2 is normally expressed in cardiovascular, lung type II alveolar epithelial cells and kidneys with tissue-specific activity patterns [1, 2] and also in the placenta [3] .

The serine protease for virus Spike (S) protein priming, TMPRSS2, was also reported to be necessary for SARS-CoV-2 cell entry [4] . ACE2 is a Renin-angiotensin system (RAS) component and controls blood pressure [5] . The angiotensin-converting enzyme-2, which is encoded by ACE2 gene, is the receptor for SARS-CoV-2 [7, 8] . Some reports showed a positive correlation between SARS-CoV infection level and ACE2 expression levels in vitro [9, 10] . The susceptibility to infection with SARS-CoV-2 may depend on ACE2 expression level and pattern in different tissues and also may be among different populations, in which the ACE2 gene sequence or expression levels need further studies.

This experiment was performed to investigate the co-relationship between the low incidence of SARS-CoV-2 and ACE2 receptor among Egyptian population. The current study was done in accordance with The Code of Ethics of the World Medical Association of Helsinki Declaration [6] and was approved by the Ethics Committee of National Cancer Institute, Cairo University. All participants signed a written informed consent. Genomic DNA was extracted from 70 peripheral blood samples from normal Egyptian participants using a QIAamp DNA Mini kit (Qiagen GmbH) according to manufacturer's instructors. In order to construct a library, exome capture was performed using an Agilent SureSelect Human All ExonV5 kit (Agilent Technologies, Inc.) according to manufacturer's protocol. In brief, a total of 0.5 µg DNA was used for DNA library preparations followed by fragmentation via sonication to ~350 bp size. Then, DNA fragments were . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted May 2, 2020. Each of the two frameshift deletions has seen only once in our population and their quality is not strong enough to support structural changes in the protein (All data are available as supplement file).

We also compared our findings to the reported variants of the Italian population. The most relevant variants in the Italian population were p.Asn720Asp, p.Lys26Arg, p.Gly211Arg, and p.Trp69Cys.

The first three variants are rare in world population in general (ExAC All 0.016, 0.001, 0.005, respectively) but the frequency in African, Middle East, and East Asian populations is much less than that of European population. Their structural damaging scores are not above the accepted threshold (CADD less than 15, and Benign PolyPhen and Sift predictions). The fourth variant is the most important and it is specific to the Italian population with high structural damaging score (CADD =23). All these four variants do not exist in our exome set of the Egyptian population.

In conclusion and as per available data, mutations in the SARS-CoV-2 receptor were not the reason for the low symptomatic incidence/death rate of the Covid-19 in Egypt. We recommend a large sample size study on the host and viral genome sequences, including potential functional coding variants in ACE2 and the gene expression levels, among Egyptian populations for further epidemiological investigations of SARS-CoV-2.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted May 2, 2020. . https://doi.org/10.1101/2020.04.27.20082206 doi: medRxiv preprint

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