key: cord-0748248-2fxqo4al authors: Sardar, Rahila; Satish, Deepshikha; Birla, Shweta; Gupta, Dinesh title: Integrative analyses of SARS-CoV-2 genomes from different geographical locations reveal unique features potentially consequential to host-virus interaction, pathogenesis and clues for novel therapies date: 2020-08-20 journal: Heliyon DOI: 10.1016/j.heliyon.2020.e04658 sha: 1b82e52085a606ea41d4b81e7825b9cb38b6280f doc_id: 748248 cord_uid: 2fxqo4al We have performed an integrative analysis of SARS-CoV-2 genome sequences from different countries. Apart from mutational analysis, we have predicted host antiviral miRNAs targeting virus genes, PTMs in the virus proteins and antiviral peptides. A comparison of the analyses with other coronavirus genomes has been performed, wherever possible. Our analysis confirms unique features in the SARS-CoV-2 genomes absent in other evolutionarily related coronavirus family genomes, which presumably confer unique infection, transmission and virulence capabilities to the virus. For understanding the crucial factors involved in host-virus interactions, we have performed Bioinformatics aided analysis integrated with experimental data related to other corona viruses. We have identified 42 conserved miRNAs that can potentially target SARS-CoV-2 genomes. Interestingly, out of these, 3 are previously reported to exhibit antiviral activity against other respiratory viruses. Gene expression analysis of known host antiviral factors reveals significant over-expression of IFITM3 and down regulation of cathepsins during SARS-CoV-2 infection, suggesting its active role in pathogenesis and delayed immune response. We also predicted antiviral peptides which can be used in designing peptide based drugs against SARS-CoV-2. Our analysis explores the functional impact of the virus mutations on its proteins and interaction of its genes with host antiviral mechanisms. The virus sequence mutation rate is one of the most fundamental aspects of its evolution in 120 response to selective pressures, which is governed by multiple processes such as polymerase The downloaded SARS-CoV-2 genomes were subjected to mutation analysis using Genome (Table S1 ). (Table S2) . Figure 1A ). These findings are in concordance with the previous findings, which 206 suggest S1 to be the highly variable region as compared to the S2 subunit. The mutation 207 D614G was conserved among various countries and was found to be located in S1, in a 208 linking region between S1 and S2. Table 237 S3). We also found 42 conserved antiviral miRNAs predicted to have targets in all the SARS- performed. There were less number of genes found to be differentially expressed in SARS- CoV-2 with respect to SARS-CoV, at 24 hr-post infection (Table S4) . 261 Interestingly, we observed interferon beta (IFN-B) , upregulated in SARS-CoV infection, is claimed that antiviral mechanism of these miRNAs will be definitely same in SARS-CoV-2. Simply put, prima facie the 12 artificial miRNA are predicted to have targets in the SARS- Table 1 : Predicted effects on the protein stability due to the mutations in the spike glycoproteins in 341 various SARS-CoV-2 genomes, using various prediction methods. 342 Table S1 : Genome variation between SARS-CoV and SARS-CoV-2. 343 Table S2 : Entropy for SARS-CoV-2 gene products and summary of mutation events in the SARS-344 CoV-2 genomes from different geographical locations. 345 Table S3 : The list of miRNAs identified in the study, using miRbase. The predicted miRNAs 346 targeting SARS-CoV, SARS-CoV-2 and MERS and the literature source of the antiviral 347 miRNAs. 348 Table S4 : Host gene expression in SARS-CoV and SARS-CoV-2 infection 349 Coronaviridae Study Group of the International Committee on Taxonomy of V. 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