Abstract
Human ACE2 and the serine protease TMPRSS2 of novel SARS-CoV-2 are primary entry receptors in host cells. Expression of these genes at the transcriptional level has not been much discussed in detail. The ISRE elements of the ACE2 promoter are a binding site for the ISGF3 complex of the JAK/STAT signaling pathway. TMPRSS2, including IFNβ, STAT1, and STAT2, has the PARP1 binding site near to TSS either up or downstream promoter region. It is well documented that PARP1 regulates gene expression at the transcription level. Therefore, to curb virus infection, both promoting type I IFN signaling to boost innate immunity and prevention of virus entry by inhibiting PARP1, ACE2 or TMPRSS2 are safe options. Most importantly, our aim is to attract the attention of the global scientific community towards the codon 72 Single Nucleotide Polymorphism (SNP) of p53 and its underneath role in the innate immune response against SARS-CoV-2. Here, we discuss codon 72 SNP of human p53′s role in the different innate immune response to restrict virus-mediated mortality rate only in specific parts of the world. In addition, we discuss potential targets and emerging therapies using bioengineered bacteriophage, anti-sense, or CRISPR strategies.
Highlights
In addition to intracellular Toll-Like Receptors (TLRs), one study reported the role of extracellular TLR4 signaling and oxidative stress subsequently reactive oxygen species (ROS) production is a key pathway of Acute Lung Injury (ALI) after SARS or H5N1 avian flu virus infection [12]
We describe and discuss the pathways that play a major role of type I IFN and JAK/STAT pathways in the regulation of angiotensin-converting enzyme 2 (ACE2) and possible DNA damage-dependent PARP1-regulated TMPRSS2 gene expression
It has been reported that transcriptional activation of the IFNβ in response to virus infection requires the assembly of an enhanceosome, which recruits the transcription factors and chromatin remodelers to slide the nucleosome over the core promoter region to a downstream position, required for transcriptional activation [45]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In addition to intracellular TLRs, one study reported the role of extracellular TLR4 signaling and oxidative stress subsequently ROS production is a key pathway of Acute Lung Injury (ALI) after SARS or H5N1 avian flu virus infection [12] Macrophages contribute to both viral control and tissue damage as well as DNA damage of virus and host cells. A conserved DNA sequence element was reported in type I ISG promoters and characterized as the IFN-stimulated response element (ISRE) [25] It is binding site of Interferon Stimulated Gene Factor 3 (ISGF3) complex, once it translocated in the nucleus after IFN pathway stimulation [26]. Gene Ontology (GO) analysis shows, majorly involves in the viral entry into the host cell, response to virus infection, virion attachment, and binding of a host cell receptor, regulation of inflammatory response, and cytokine production (Table 1). A low p value * (less than 0.05) for an ontological term indicates a low probability that so many hits to that term would have been observed if the results had been due to random effects, and such terms might be considered to be enriched in the results [35,36]
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