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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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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. short segments of amino acids in the HIV-1 gp120 and Gag among all annotated virus proteins in the NCBI database. This uncanny similarity of novel inserts in the 2019- nCoV spike protein to HIV-1 gp120 and Gag is unlikely to be fortuitous. Further, 3D modelling suggests that atleast 3 of the unique inserts which are non-contiguous in the primary protein sequence of the 2019-nCoV spike glycoprotein converge to constitute the key components of the receptor binding site. Of note, all the 4 inserts have pI values of around 10 that may facilitate virus-host interactions. Taken together, our findings suggest unconventional evolution of 2019-nCoV that warrants further investigation. Our work highlights novel evolutionary aspects of the 2019-nCoV and has implications on the pathogenesis and diagnosis of this virus. References References Beniac, D. R., Andonov, A., Grudeski, E., & Booth, TaF. (2006). Architecture of the SARS coronavirus prefusion spike. Nature Structural and Molecular Biology, 13(8), 751-752. https://doi.org/10.1038/nsmb1123 Biasini, M., BienertgS., Waterhouse, A., Arnold, K., Studer, Gs, Schmidt, T., Kiefer, F., Cassarino, T. G., Bertoni, M., Bordoli, L., & Schwede, T. (2014). SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Research. https://doi.org/10.1093/nar/gku340 Bosch, B.J., van der Zee, R., de(Haan, C. A. M., & Rottier, P. J. M. (2003). The Coronavirus Spike Protein Is a Class | Virus Fusion’Protein: Structural and Functional Characterization of the Fusion Core Complex. Journal of Virology, 77(16), 8801-8811. https://doi.org/10.1128/jvi.77.16.8801- 8811.2003 References Chan, J. F.-W., Kok, K.-H., Zhu, Z., Chu, H., To, K. K.-W., Yuan, S., & Yuen, K.-Y. (2020). Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging Microbes & Infections, 9(1), 221-236. https://doi.org/10.1080/22221751.2020.1719902 Chan, J. F. W., Lau, S. K. P., To, K. K. W., Cheng, V. C. C., Woo, P. C. Y., & Yuen, K.-Y. (2015). Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease. https://doi.org/10.1128/CMR.00102-14 Chan, J., To, K., Tse, H., Jin, D., microbiology, K. Y.-T. in, & 2013, undefined. (n.d.). Interspecies transmission and emergence of novel viruses: lessons from bats and birds. Elsevier. Corpet, F. (1988). Multiple sequence alignment with hierarchical clustering. Nucleic Acids Research. https://doi.org/10.1093/nar/16.22.10881 DeLano, W. L. (2002). The PYMOL Molecular Graphics System, Version 1.1. Schr{6}dinger LLC. https://doi.org/10.1038/hr.2014.17 Du, L., Zhao, G., Kou, Z., Ma, C., Sun, S., Poon, V. K. M., Lu, L., Wang, L., Debnath, A. K., Zheng, B.-J., Zhou, Y., & Jiang, S. (2013). Identification of a Receptor-Binding Domain in the S Protein of the Novel Human Coronavirus Middle East Respiratory Syndrome Coronavirus as an Essential Target for Vaccine Development. Journal of Virology, 87(17), 9939-9942. https://doi.org/10.1128/jvi.01048- 13