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OBJECTIVE: Rapid transmission and reproduction of RNA viruses prepare conducive conditions to have a high rate of mutations in their genetic sequence. The viral mutations make adapt the severe acute respiratory syndrome coronavirus 2 in the host environment and help the evolution of the virus then also caused a high mortality rate by the virus that threatens worldwide health. Mutations and adaptation help the virus to escape confrontations that are done against it. METHODS: In the present study, we analyzed 6,510,947 sequences of non-structural protein 1 as one of the conserved regions of the virus to find out frequent mutations and substitute amino acids in comparison with the wild type. NSP1 mutations rate divided into continents were different. RESULTS: Based on this continental categorization, E87D in global vision and also in Europe notably increased. The E87D mutation has signed up to January 2022 as the first frequent mutation observed. The remarkable mutations, H110Y and R24C have the second and third frequencies, respectively. CONCLUSION: According to the important role of non-structural protein 1 on the host mRNA translation, developing drug design against the protein could be so hopeful to find more effective ways the control and then treatment of the global pandemic coronavirus disease 2019.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unsegmented positivesense single-stranded RNA virus that belongs to the ß-coronavirus . This virus was the cause of a novel severe acute respiratory syndrome in 2019 (COVID-19) that emerged in Wuhan, China at the early stage of the pandemic and rapidly spread around the world. Rapid transmission and reproduction of SARS-CoV-2 threaten worldwide health with a high mortality rate from the virus. According to the significant role of non-structural protein 1 (NSP1) in inhibiting host mRNA translation, this study focuses on the link between amino acid sequences of NSP1 and alterations of them spreading around the world. The SARS-CoV-2 NSP1 protein sequences were analyzed and FASTA files were processed by Python language programming libraries. Reference sequences compared with each NSP1 sample to identify every mutation and categorize them were based on continents and frequencies. NSP1 mutations rate divided into continents were different. Based on continental studies, E87D in global vision and also in Europe notably increased. The E87D mutation has significantly risen especially in the last months of the study as the first frequent mutation observed. The remarkable mutations, H110Y and R24C, have the second and third frequencies, respectively. Based on this mutational information, despite NSP1 being a conserved sequence occurrence, these mutations change the rate of flexibility and stability of the NSP1 protein, which can eventually affect inhibiting the host translation. IMPORTANCE: In this study, we analyzed 6,510,947 sequences of non-structural protein 1 as a conserved region of SARS-CoV-2. According to the obtained results, 93.4819% of samples had no mutant regions on their amino acid sequences. Heat map data of mutational samples demonstrated high percentages of mutations that occurred in the region of 72 to 126 amino acids indicating a hot spot region of the protein. Increased rates of E87D, H110Y, and R24C mutations in the timeline of our study were reported as significant compared to available mutant samples. Analyzing the details of replacing amino acids in the most frequent E87D mutation reveals the role of this alteration in increasing molecule flexibility and destabilizing the structure of the protein.
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Senile ages of human life is mostly associated with developmental of several neurological complicated conditions including decreased cognition and reasoning, increased memory loss and impaired language performance. Alzheimer's disease (AD) is the most prevalent neural disorder associated with dementia, consisting of about 70% of dementia reported cases. Failure of currently approved chemical anti-AD therapeutic agents has once again brought up the idea of administering naturally occurring compounds as effective alternative and/or complementary regimens in AD treatment. Polyphenol structured neuroprotecting agents are group of biologically active compounds abundantly found in plants with significant protecting effects against neural injuries and degeneration. As a subclass of this family, Flavonoids are potent anti-oxidant, anti-inflammatory and signalling pathways modulatory agents. Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) pathways are both affected by Flavonoids. Regulation of pro-survival transcription factors and induction of specific genes expression in hippocampus are other important anti AD therapeutic activities of Flavonoids. These agents are also capable of inhibiting specific enzymes involved in phosphorylation of tau proteins including ß-secretases, cyclin dependent kinase 5 and glycogen synthase. Other significant anti AD effects of Flavonoids include neural rehabilitation and lost cognitive performance recovery. In this review, first we briefly describe the pathophysiology and important pathways involved in pathology of AD and then describe the most important mechanisms through which Flavonoids demonstrate their significant neuroprotective effects in AD therapy.
