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bioRxiv preprint doi: https://doi.org/10.1101/2020.01.30.927871; this version posted January 31, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. and Gag Prashant Pradhan*!?, Ashutosh Kumar Pandey*!, Akhilesh Mishra*!, Parul Gupta!, Praveen Kumar Tripathi!, Manoj Balakrishnan Menon!, James Gomes', Perumal Vivekanandan*!and Bishwajit Kundu*! 'Kusuma School of biological sciences, Indian institute of technology, New Delhi-110016, India. Acharya Narendra Dev College, University of Delhi, New Delhi-110019, India SEqual contribution * Corresponding authors- email: bkundu @biosehool.iitd.ac.in vperumal @ bioschool.iitd.ac.in Abstract: Abstract: We are currently witnessing a major epidemic caused by the 2019 novel coronavirus (2019- nCoV). The,evolution of 2019-nCoV remains~elusive. We found 4 insertions in the spike glycoprotein (S) which are unique,to the 2019-nCoV and are not present in other coronaviruses. Importantly, amino acid residués‘in all the 4 inserts have identity or similarity to those in the HIV- 1 gp120 or HIV-1 Gag: Interestingly, despite the inserts being discontinuous on the primary amino acid sequence, 3D-modelling of the 2019-nCoV suggests that they converge to constitute the receptor binding site. The finding of 4 unique inserts in the 2019-nCoV, all of which have identity /similarity to amino acid residues in key structural proteins of HIV-1 is unlikely to be fortuitous in nature. This work provides yet unknown insights on 2019-nCoV and sheds light on the evolution and pathogenicity of this virus with important implications for diagnosis of this virus. Abstract: Introduction Coronaviruses (CoV) are single-stranded positive-sense RNA viruses that infect animals and humans. These are classified into 4 genera based on their host specificity: Alphacoronavirus, Betacoronavirus, Deltacoronavirus and Gammacoronavirus (Snijder et al., 2006). There are seven known types of CoVs that includes 229E and NL63 (Genus Alphacoronavirus), OC43, HKU1, MERS and SARS (Genus Betacoronavirus). While 229E, NL63, OC43, and HKU1 commonly infect humans, the SARS and MERS outbreak in 2002 and 2012 respectively occurred when the virus crossed-over from animals to humans causing significant mortality (J. Chan et al., n.d.; J. F. W. Chan et al., 2015). In December 2019, another outbreak of coronavirus was reported from Wuhan, China that also transmitted from animals to humans. This new virus has been temporarily termed as 2019-novel Coronavirus (2019-nCoV) by the World Health Organization (WHO) (J. F.- W. Chan et al., 2020; Zhu et al. » 2020). While there | are several hypotheses about the origin of The transmission patterns of 2019-nCoV is similar to patterns of transmission documented in the previous outbreaks including by bodily or aerosol contact with persons infected with the virus. Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 SEqual contribution 2019-nCoV, the source of this ongoing outbreak remains elusive.