TY - JOUR T1 - Multi-Omics and Integrated Network Approach to Unveil Evolutionary Patterns, Mutational Hotspots, Functional Crosstalk and Regulatory Interactions in SARS-CoV-2 JF - bioRxiv DO - 10.1101/2020.06.20.162560 SP - 2020.06.20.162560 AU - Vipin Gupta AU - Shaiza Haider AU - Mansi Verma AU - Kalaiarasan Ponnusamy AU - Md. Zubbair Malik AU - Nirjara Singhvi AU - Helianthous Verma AU - Roshan Kumar AU - Utkarsh Sood AU - Princy Hira AU - Shiva Satija AU - Rup Lal Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/20/2020.06.20.162560.abstract N2 - SARS-CoV-2 responsible for the pandemic of the Severe Acute Respiratory Syndrome resulting in infections and death of millions worldwide with maximum cases and mortality in USA. The current study focuses on understanding the population specific variations attributing its high rate of infections in specific geographical regions which may help in developing appropriate treatment strategies for COVID-19 pandemic. Rigorous phylogenetic network analysis of 245 complete SARS-CoV-2 genomes inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2) showing both divergent and linear evolution types. The clade d & e2 were found exclusively comprising of USA strains with highest known mutations. Clades were distinguished by ten co-mutational combinations in proteins; Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6 generated by Amino Acid Variations (AAV). Our analysis revealed that only 67.46 % of SNP mutations were carried by amino acid at phenotypic level. T1103P mutation in Nsp3 was predicted to increase the protein stability in 238 strains except six strains which were marked as ancestral type; whereas com (P5731L & Y5768C) in Nsp13 were found in 64 genomes of USA highlighting its 100% co-occurrence. Docking study highlighted mutation (D7611G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor which may contribute to its high transmissibility in USA strains. In addition, we found host proteins, MYO5A, MYO5B & MYO5C had maximum interaction with viral hub proteins (Nucleocapsid, Spike & Membrane). Thus, blocking the internalization pathway by inhibiting MYO-5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the Host-Pathogen Interaction (HPI) network were found to be highly associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection in the patients. We also considered the presence of CpG islands in Nsp1 and N proteins which may confers the ability of SARS-CoV-2 to enter and trigger methyltransferase activity inside host cell.Competing Interest StatementThe authors have declared no competing interest. ER -