Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans

Xue, X.; Shi, J.; Xu, H.; Qin, Y.; Yang, Z.; Feng, S.; Liu, D.; Jian, L.; Hua, L.; Wang, Y.; Zhang, Q.; Huang, X.; Zhang, X.; Li, X.; Chen, C.; Guo, J.; Tang, W.; Liu, J.

doi:10.1101/2020.06.25.170704

bioRxiv · 10.1101/2020.06.25.170704

Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans

Xue, X.·Shi, J.·Xu, H.·Qin, Y.·Yang, Z.·Feng, S.·Liu, D.·Jian, L.·Hua, L.·Wang, Y.·Zhang, Q.·Huang, X.·Zhang, X.·Li, X.·Chen, C.·Guo, J.·Tang, W.·Liu, J.

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Abstract

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing an outbreak of COVID-19 globally in the past six months. A relatively higher divergence on the spike protein of SASR-CoV-2 enables it to transmit across species efficiently. We particularly believe that the adaptive mutations of the receptor-binding domain (RBD) of spike protein in SARS-CoV-2 might be essential to its high transmissibility among humans. Thus here we collected 2,142 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny, and also analyzed the interaction between the polymorphisms of spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 and coronavirus in other hosts show SARS-CoV-2 is highly possible originated from Bat-CoV (RaTG13) found in horseshoe bat and a recombination event may occur on the spike protein of Pangolin-CoV to imbue it the ability to infect humans. Moreover, compared to the S gene of SARS-CoV-2, it is more conserved in the direct-binding sites of RBD and we noticed that spike protein of SARS-CoV-2 may under a consensus evolution to adapt to human hosts better. 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 were simulated and their stability and affinity binding to hACE2 (S19-D615) were calculated. Our analysis indicates SARS-CoV-2 could infect humans from different populations with no preference, and a higher divergence in the spike protein of SARS-CoV-2 at the early stage of this pandemic may be a good indicator that could show the pathway of SARS-CoV-2 transmitting from the natural reservoir to human beings.

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Xue, X., Shi, J., Xu, H., Qin, Y., Yang, Z., Feng, S., Liu, D., Jian, L., Hua, L., Wang, Y., Zhang, Q., Huang, X., Zhang, X., Li, X., Chen, C., Guo, J., Tang, W., Liu, J.. 2020-06-27. Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans. https://doi.org/10.1101/2020.06.25.170704

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