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Open AccessArticle

Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements

1
Emerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USA
2
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
3
Laboratory of Transmissible Diseases and Biological Active Substances LR99ES27, Faculty of Pharmacy, University of Monastir, Rue Ibn Sina, 5000 Monastir, Tunisia
4
Department of Biotechnology, High Institute of Biotechnology of Sidi Thabet, University of Manouba, BP-66, 2020 Ariana-Tunis, Tunisia
5
Department for Innovation in Biological, Agro-food and Forest Systems (DIBAF), University of Tuscia, via S. Camillo de Lellis s.n.c., 01100 Viterbo, Italy
6
Institute for Biological Systems, National Research Council, Via Salaria, Km 29.500, 00015 Monterotondo, Rome, Italy
7
Department of Biology, Temple University, Philadelphia, PA 19122, USA
8
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council, Via Giovanni Amendola, 122/O, 70126 Bari, Italy
*
Authors to whom correspondence should be addressed.
Authors contributed equally as first to this work.
Authors contributed equally as last to this work.
Int. J. Mol. Sci. 2021, 22(1), 80; https://doi.org/10.3390/ijms22010080
Received: 31 October 2020 / Revised: 17 December 2020 / Accepted: 18 December 2020 / Published: 23 December 2020
Our evolutionary and structural analyses revealed that the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) spike gene is a complex mosaic resulting from several recombination events. Additionally, the fixation of variants has mainly been driven by purifying selection, suggesting the presence of conserved structural features. Our dynamic simulations identified two main long-range covariant dynamic movements of the novel glycoprotein, and showed that, as a result of the evolutionary duality, they are preserved. The first movement involves the receptor binding domain with the N-terminal domain and the C-terminal domain 2 and is maintained across human, bat and pangolin coronaviruses. The second is a complex network of long-range dynamics specific to SARS-CoV-2 involving the novel PRRA and the conserved KR*SF cleavage sites, as well as conserved segments in C-terminal domain 3. These movements, essential for host cell binding, are maintained by hinges conserved across human, bat, and pangolin coronaviruses glycoproteins. The hinges, located around Threonine 333 and Proline 527 within the N-terminal domain and C-terminal domain 2, represent candidate targets for the future development of novel pan-coronavirus inhibitors. In summary, we show that while recombination created a new configuration that increased the covariant dynamic movements of the SARS-CoV-2 glycoprotein, negative selection preserved its inter-domain structure throughout evolution in different hosts and inter-species transmissions. View Full-Text
Keywords: SARS-CoV-2; COVID-19; recombination; furin-like cleavage site; ACE2; S glycoprotein; molecular dynamics; bioinformatics SARS-CoV-2; COVID-19; recombination; furin-like cleavage site; ACE2; S glycoprotein; molecular dynamics; bioinformatics
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MDPI and ACS Style

Tagliamonte, M.S.; Abid, N.; Borocci, S.; Sangiovanni, E.; Ostrov, D.A.; Kosakovsky Pond, S.L.; Salemi, M.; Chillemi, G.; Mavian, C. Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements. Int. J. Mol. Sci. 2021, 22, 80.

AMA Style

Tagliamonte MS, Abid N, Borocci S, Sangiovanni E, Ostrov DA, Kosakovsky Pond SL, Salemi M, Chillemi G, Mavian C. Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements. International Journal of Molecular Sciences. 2021; 22(1):80.

Chicago/Turabian Style

Tagliamonte, Massimiliano S.; Abid, Nabil; Borocci, Stefano; Sangiovanni, Elisa; Ostrov, David A.; Kosakovsky Pond, Sergei L.; Salemi, Marco; Chillemi, Giovanni; Mavian, Carla. 2021. "Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements" Int. J. Mol. Sci. 22, no. 1: 80.

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