Analysis of Indian SARS-CoV-2 Genomes Reveals Prevalence of D614G Mutation in Spike Protein Predicting an Increase in Interaction With TMPRSS2 and Virus Infectivity

Sunil Raghav, Arup Ghosh, Jyotirmayee Turuk, Sugandh Kumar, Atimukta Jha, Swati Madhulika, Manasi Priyadarshini, Viplov K. Biswas, P. Sushree Shyamli, Bharati Singh, Neha Singh, Deepika Singh, Ankita Datey, Kiran Avula, Shuchi Smita, Jyotsnamayee Sabat, Debdutta Bhattacharya, Jaya Singh Kshatri, Dileep Vasudevan, Amol Suryawanshi, Rupesh Dash, Shantibhushan Senapati, Tushar K. Beuria, Rajeeb Swain, Soma Chattopadhyay, Gulam Hussain Syed, Anshuman Dixit, Punit Prasad, Odisha COVID-19 Study Group, ILS COVID-19 Team, Sanghamitra Pati, Ajay Parida, Arvind Kumar Singh, Baijayantimala Mishra, Banajini Parida, Binod Kumar Patro, D. P. Dogra, Dasarathi Das, Deepa Prasad, Dhaneswari Jena, Dharitri Mohapatra, Dinesh Prasad Sahu, Durga Madhab Satapathy, Durgesh Prasad Sahoo, Jayanta Panda, Jaya Singh Khatri, Kaushik Mishra, Manoranjan Satpathy, Nirupama Chaini, Roma Rattan, Sadhu Panda, Sangeeta Das, Somen Kumar Pradhan, Srikanta Kanungo, Sriprasad Mohanty, Subrata Kumar Palo, Aditi Chatterjee, Adyasha Mishra, Ajit Kumar Singh, Amrita Ray, Ankita Datey, Aliva Minz, Ashish Yadav, Auromira Khuntia, Anshuman Dixit, Debyashreeta Barik, Deepak Singh, Eshna Laha, Hiren G. Dodia, Jeky Chawla, Kautilya Jena, Kaushik Sen, Niyati Das, Omprakash Shriwas, P. M. Vaishali, Parej Nath, Paritosh Nath, Prabhudutta Mamidi, Priyanka Mohapatra, Rahul Das, Rina Yadav, Sachikanta Rout, Saikat De, Sanchari Chatterjee, Sandhya Suranjika, Satyaranjan Sahoo, Shamima Ansari, Shifu Aggarwal, Shiva Pradhan, Sivaram Krishna, Sneha Dutta, Soumendu Mahapatra, Soumyajit Gosh, Subhabrata Barik, Sudhir Boral, Supriya Suman Keshry, Swatismita Priyadarshini, Tsheten Sherpa

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has emerged as a global pandemic worldwide. In this study, we used ARTIC primers-based amplicon sequencing to profile 225 SARS-CoV-2 genomes from India. Phylogenetic analysis of 202 high-quality assemblies identified the presence of all the five reported clades 19A, 19B, 20A, 20B, and 20C in the population. The analyses revealed Europe and Southeast Asia as two major routes for introduction of the disease in India followed by local transmission. Interestingly, the19B clade was found to be more prevalent in our sequenced genomes (17%) compared to other genomes reported so far from India. Haplotype network analysis showed evolution of 19A and 19B clades in parallel from predominantly Gujarat state in India, suggesting it to be one of the major routes of disease transmission in India during the months of March and April, whereas 20B and 20C appeared to evolve from 20A. At the same time, 20A and 20B clades depicted prevalence of four common mutations 241 C > T in 5' UTR, P4715L, F942F along with D614G in the Spike protein. D614G mutation has been reported to increase virus shedding and infectivity. Our molecular modeling and docking analysis identified that D614G mutation resulted in enhanced affinity of Spike S1-S2 hinge region with TMPRSS2 protease, possibly the reason for increased shedding of S1 domain in G614 as compared to D614. Moreover, we also observed an increased concordance of G614 mutation with the viral load, as evident from decreased Ct value of Spike and the ORF1ab gene.