Virus research
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Role of the GTNGTKR motif in the N-terminal receptor-binding domain of the SARS-CoV-2 spike protein.
The 2019 novel coronavirus disease (COVID-19) that emerged in China has been declared as public health emergency of international concern by the World Health Organization and the causative pathogen was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, we analyzed the structural characteristics of the N-terminal domain of the S1 subunit (S1-NTD) of the SARS-CoV-2 spike protein in comparison to the SARS-CoV in particular, and to other viruses presenting similar characteristic in general. ⋯ In particular, motifs similar to the insertion 72GTNGTKR78 have been found in structural proteins of other viruses; and these motifs were located in putative regions involved in recognizing protein and sugar receptors, suggesting therefore that similar binding abilities could be displayed by the SARS-CoV-2 S1-NTD. Moreover, concerning the origin of these NTD insertions, our findings point towards an evolutionary acquisition rather than the hypothesis of an engineered virus.
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Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. ⋯ Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies.
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Although several miRNAs have been demonstrated to be involved in the influenza virus replication cycle, the identification of miRNAs and mRNAs that are expressed in A549 cells infected with influenza A viruses (IAVs) from different host species has remained poorly studied. To investigate the molecular mechanisms associated with the differential expression of miRNAs during influenza A virus infection, we performed global miRNA and mRNA expression profiling in A549 cells infected with human-origin seasonal influenza A virus H3N2 (Human_Br07), swine-origin influenza A virus H1N1 (SW_3861) or avian-origin influenza A virus H3N2 (AVI_9990). The miRNA and mRNA expression profiles were obtained by microarray and high-throughput sequencing analyses, respectively. ⋯ An integrated analysis of these expression profiles identified 79 miRNA-mRNA pairs associated with the influenza A reference pathway, and 107 miRNA-mRNA interactions were correlated with the defense of the virus. Additionally, the obtained results were supported by an RT-qPCR analysis of 8 differentially expressed miRNAs (hsa-miR-210-3p, hsa-miR-296-5p, hsa-miR-371a-5p, hsa-miR-762, hsa-miR-937-5p, hsa-miR-1915-3p, hsa-miR-3665, and hsa-miR-1290) and 13 differentially expressed mRNAs (IFNL1, CXCL10, RSAD2, MX1, OAS2, IFIT2, IFI44 L, MX2, XAF1, NDRG1, FGA, EGLN3, and TFRC). Our findings indicate that dysregulated miRNA expression plays a crucial role in infection caused by IAVs originating from different species and provide a foundation for further investigations of the molecular regulatory mechanisms of miRNAs involved in influenza A virus infection.
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Zika virus (ZIKV) is an Aedes mosquitoes-transmitted flavivirus, and its infection may cause severe neurological diseases. A genetically stable infectious clone is essential for ZIKV research, however the toxicity and instability of the viral cDNA in bacteria potentially due to its bacterial promoter activity are major challenges. Here, we constructed a full-length cDNA clone for isolate ZG01 by introducing non-coding changes T1865C/A1868G to reduce the bacterial promoter activity. ⋯ Notably, ZG01_4m plasmid was genetically stable after multiple rounds of transformation-purification in bacteria. Using ZG01_4m, we identified a potential RNA-RNA interaction between 5'UTR and 3'UTR and demonstrated that the nucleotides involved were essential for ZIKV production. The genetically stable ZG01 cDNA clone provides a reliable tool for the study of this important virus, and the strategy used here is feasible for the development of reverse genetics systems for other ZIKV isolates and related flaviviruses.