key: cord-0789776-olq6abpl authors: Komurcu, Selen Zeliha Mart; Artik, Yakup; Cesur, Nevra Pelin; Tanriverdi, Arzu; Erdogan, Derya Cakir; Celik, Sule; Gulec, Elif Yilmaz title: The evaluation of potential global impact of the N501Y mutation in SARS‐COV‐2 positive patients date: 2021-11-01 journal: J Med Virol DOI: 10.1002/jmv.27413 sha: aec41c1e26921976e6a987a11305b1d05d708548 doc_id: 789776 cord_uid: olq6abpl Rapid and reliable detection of severe acute respiratory syndrome coronavirus 2 mutations are significant to control the contagion and spread rate of the virus. We aimed to evaluate the N501Y mutation rate in randomly chosen positive patients with the polymerase chain reaction (PCR). The evaluation and analysis of the data with a retrospective approach in cases with mutations, in terms of public health, will contribute to the literature on the global pandemic that affects our society. Public health authorities will take the necessary precautions and evaluate the current situation. The N501Y mutation was detected in patients with positive Covid‐19 PCR test results. The positive samples were examined based on the 6‐carboxy‐fluorescein (FAM) channel in reverse transcription PCR (RT‐PCR) quantitation cycle (Cq) values as low Cq (<25), medium Cq (25–32), and high Cq (32–38) groups. In the study, 2757 (19.7%) of 13 972 cases were detected as mutation suspects and 159 (5.8%) of them were found to have mutations. The ages of the cases with mutations ranged from 1 to 88 years (mean age of 40.99 ± 17.55). 49.7% (n = 79) of the cases with mutations were male, and 50.3% (n = 80) were female. When the RT‐PCR‐Cq results were examined, it was seen that it varied between 11.3 and 35.03, with an average of 20.75 ± 3.32. Three types of coronavirus have plagued humans since the early 21st century; severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and finally severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 1 December 2019, has caused a pandemic all over the world, which infected more than 146 billion and killed more than 3 billion people. 2 The disease of the SARS-CoV-2 is called COVID-19. Globally, there have been 192 284 207 confirmed cases of COVID-19 including 4 136 518 deaths reported by the World Health Organization (WHO). As of July 19, 2021, a total of 3 568 861 733 vaccine doses have been administered. 3 The SARS-CoV-2 transmits from person to person through droplets, contaminated objects, and also direct contact. The symptoms of COVID-19 are described as fever, throat, tiredness, cough, and sore. 4 The average incubation time was detected as 5.2 days and this information was updated as 6.4 days with new studies. 5 The coronavirus family are positively stranded enveloped RNA viruses. They can be mainly classified into four genera such as beta, observed in these regions. places globally such as South Africa, 11 Brazil, 12 and the United States. 13 For both variants, the mutation in the RBD region of SARS-CoV-2 is described by the N501Y mutation. On the other hand, in B. 1.351 lineage, the K417N, and E484K mutations are found in the RBD region. 14 Three mutations in the S protein of the novel variant (N501Y, HV69-70del, and P681H) have potential biological implications. P681H is adjacent to the furin cleavage site, a location known to be of biological importance. HV69-70del located in the N-terminal domain (NTD) has been identified in variants associated with immune escape in immunocompromised patients. 15 The N501Y is located in the receptor binding motif (RBM) of the C-terminal domain (CTD) and has been found to increase its binding affinity to human ACE2 receptor as shown in Figure 1 . The gene target is 500 copies/ml, while that of the N501, Y501 targets are 5000 copies/ml. Additionally, for the N501Y mutation test interpretation, various situations were obtained as summarized in Table 2 . Number Cruncher Statistical System Statistical Software program was used for statistical analysis. When evaluating the study data, Mann-Whitney U test was used for the comparisons between groups of nonnormally distributed parameters. Spearman's correlation analysis was used to evaluate the relationships between age and test results. Significance was evaluated at the p < 0.05 level. Domain architecture of the SARS-CoV-2 spike monomer is showed in Table 3 . The N501Y is located in the RBM of the CTD and has been found to increase its binding affinity to human ACE2; as mutations in the CTD of the S protein (aa 333-527) are most likely to alter the receptor recognition properties of SARS-CoV-2. As shown in Figure 2 , 10 exact amino acid changes were described for N501Y mutation. Additionally, the difference between general SARS-CoV-2 and N501Y mutation sequence is determined by sequence alignment with NGS technology as shown in Figure 3 . 21 Therefore, we aimed that these mutations are within the RBD region, understanding the new variants' binding mechanism to ACE2 receptor is of great value. With this study, the data of mutation type of SARS-CoV-2 and statistically informative preliminary study, and risk management studies can be carried out for another variant in the light of these data. In this study, special thanks to Bioeksen R&D Technologies, also Prof. Dr. Gülay Korukluoğlu and Bio. Dr. Fatma Bayraktar whose helped in NGS studies. The authors declare that there are no conflict of interests. The research was conducted ethically in accordance with the World Effect of different storage conditions on covid-19 RT-PCR results COVID-19 infection: origin, transmission, and characteristics of human coronaviruses CoV-2: an emerging coronavirus that causes a global threat The epidemiology, diagnosis and treatment of COVID-19 Coronaviruses -drug discovery and therapeutic options GISAID global initiative on sharing all influenza data. Phylogeny of SARS-like betacoronaviruses including novel coronavirus (NCoV) Structure of the SARS-CoV-2 spike receptorbinding domain bound to the ACE2 receptor Structure, function, and evolution of coronavirus spike proteins Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction Introduction of the South African SARS-CoV-2 variant 501Y. V2 into the UK Transmission of SARS-CoV-2 lineage B. 1.1. 7, Brazil Emergence of SARS-CoV-2 b. 1.1. 7 lineage-United States Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom Two-Step Strategy for the Identification of SARS-CoV-2 Variant of Concern 202012/01 and Other Variants with Spike Deletion H69-V70, France Investigation of Novel SARS-CoV-2 Variant Variant of Concern Disparities in detection of antibodies against Hepatitis E virus in US blood donor samples using commercial assays Structural and functional basis of SARS-CoV-2 entry by using human ACE2 Distinct Patterns of Emergence of SARS-CoV-2 Spike Variants Including N501Y in Clinical Samples in Columbus Ohio