Introduction: Coronavirus infectious disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenassociated molecular patterns (PAMPs) can be detected by host pattern-recognition receptors (PRRs) expressed in inherent immune cells. The polymorphisms in PRRs leads to different recognizing and immune responses against viral infections. Methods: Single-nucleotide polymorphisms of PRRs, minor allele frequency (MAF), and their geographical distribution were obtained from the Ensembl genome database. Interaction between the common polymorphic forms of PRRs (including TLR3, TLR7, RIG-1, and MDA-5) and SARS-CoV-2 virus genome (dsRNA) were predicted using the hybrid protein-RNA docking algorithm HDOCK server. Also, the global distribution of common SNPs and their MAFs were statistically analyzed using SPSS, ver.16. Results: The wild-type TLR3 and TLR3 SNP rs73873710 had the same docking energy score (-330.48 kcal/mol), and had lower docking energy scores compared to the other two SNPs, rs3775290 and rs3775291 (-301.42 and-295.81 kcal/mol, respectively). TLR7 SNP rs179008 had a higher docking energy score (-423.03 kcal/mol), comparing to the wild-type TLR7 (-445.46 kcal/mol). Also, there was a statistically significant direct relationship between MAF of TLR3 SNP rs3775290 and rs3775291 with SARS-CoV-2 prevalence (P=0.021 and P=0.023, respectively) and prevalence/population ratio of COVID-19 (P=0.026 and P<0.001, respectably). Conclusion: Wild-type TLR3 and TLR3 SNP rs73873710 can recognize the SARS-CoV-2 dsRNA genome through a better performance compared to TLR3 SNP rs3775290 and TLR3 SNP rs3775291. Therefore, our in-silico study established that PRRs SNPs are associated with antiviral responses against SARS-CoV-2.
In the last 2 decades, a wide variety of studies have been conducted on epigenetics and its role in various cancers. A major mechanism of epigenetic regulation is DNA methylation, including aberrant DNA methylation variations such as hypermethylation and hypomethylation in the promoters of critical genes, which are commonly detected in tumors and mark the early stages of cancer development. Therefore, epigenetic therapy has been of special importance in the last decade for cancer treatment. In epigenetic therapy, all efforts are made to modulate gene expression to the normal status. Importantly, recent studies have shown that epigenetic therapy is focusing on the new gene editing technology, CRISPR-Cas9. This tool was found to be able to effectively modulate gene expression and alter almost any sequence in the genome of cells, resulting in events such as a change in acetylation, methylation, or histone modifications. Of note, the CRISPR-Cas9 system can be used for the treatment of cancers caused by epigenetic alterations. The CRISPR-Cas9 system has greater advantages than other available methods, including potent activity, easy design and high velocity as well as the ability to target any DNA or RNA site. In this review, we described epigenetic modulators, which can be used in the CRISPR-Cas9 system, as well as their functions in gene expression alterations that lead to cancer initiation and progression. In addition, we surveyed various species of CRISPR-dead Cas9 (dCas9) systems, a mutant version of Cas9 with no endonuclease activity. Such systems are applicable in epigenetic therapy for gene expression modulation through chemical group editing on nucleosomes and chromatin remodeling, which finally return the cell to the normal status and prevent cancer progression.
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