Comparative Genomic Analysis of Rapidly Evolving SARS CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution
Roshan Kumar, Helianthous Verma, Nirjara Singhvi, Utkarsh Sood, Vipin Gupta, Mona Singh, Rashmi Sharma, Princy Hira, Shekhar Nagar, Chandni Talwar, Namita Nayyar, Shailly Anand, Charu Dogra Rawat, Mansi Verma, Ram Kishan Negi, Yogendra Singh, Rup Lal
doi: https://doi.org/10.1101/2020.03.25.006213
Abstract
The Coronavirus disease -19 (COVID19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 14,500 lives and has impacted human lives worldwide. Development of universal vaccines against the novel SARS-CoV-2 holds utmost urgency to control COVID19 pandemic that appears to be more severe than any of the previous outbreaks of severe acute respiratory syndrome (SARS) and Middle-East respiratory syndrome (MERS). However, as the novel SARS-CoV-2 displays high transmission rates, the underlying severity hidden in the SARS-CoV2 genomes is required to be fully understood. We studied the complete genomes of 95 strains of SARS-CoV-2 reported from different geographical regions worldwide to uncover the pattern of spread of the novel SARS-CoV-2 across the globe. We show that there is no direct transmission pattern of the virus among neighbouring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13, nsp14, nsp15, nsp16 (present in ORF1b polyprotein region) and S-Protein within 10 viral isolates from USA. These viral proteins are involved in RNA replication and processing, indicating highly evolved strains of the novel SARS-CoV-2 circulating in the population of USA than in other countries. Furthermore, we found an isolate from USA (MT188341) to carry frameshift mutation between positions 2540 and 2570 of nsp16 which functions as mRNA cap-1 methyltransferase (2′-O-MTase). Thus, we reason that the replicative machinery of the novel SARS-CoV-2 is fast evolving to evade host challenges and survival. These mutations are needed to be considered, otherwise it will be difficult to develop effective treatment strategies. The two proteins also had dN/dS values approaching 1- ORF1ab polyprotein (dN/dS= 0.996, 0.575) and S protein (dN/dS= 0.88) and might confer selective advantage to the virus. Through the construction of SARS-CoV-2-human interactome, we further reveal multiple host proteins (PHB, PPP1CA, TGF-beta, JACK1, JACK2, SOCS3,STAT3, JAK1-2, SMAD3, BCL2, CAV1 & SPECC1) which are manipulated by the virus proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune mechanism for its survival.
