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Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements.
Int J Mol Sci. 2020 Dec 23; 22(1)IJ

Abstract

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.

Authors+Show Affiliations

Emerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USA. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.Laboratory of Transmissible Diseases and Biological Active Substances LR99ES27, Faculty of Pharmacy, University of Monastir, Rue Ibn Sina, 5000 Monastir, Tunisia. Department of Biotechnology, High Institute of Biotechnology of Sidi Thabet, University of Manouba, BP-66, 2020 Ariana-Tunis, Tunisia.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. Institute for Biological Systems, National Research Council, Via Salaria, Km 29.500, 00015 Monterotondo, Rome, Italy.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.Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.Department of Biology, Temple University, Philadelphia, PA 19122, USA.Emerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USA. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.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. Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council, Via Giovanni Amendola, 122/O, 70126 Bari, Italy.Emerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USA. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33374797

Citation

Tagliamonte, Massimiliano S., et al. "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, vol. 22, no. 1, 2020.
Tagliamonte MS, Abid N, Borocci S, et al. Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements. Int J Mol Sci. 2020;22(1).
Tagliamonte, M. S., Abid, N., Borocci, S., Sangiovanni, E., Ostrov, D. A., Kosakovsky Pond, S. L., Salemi, M., Chillemi, G., & Mavian, C. (2020). 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, 22(1). https://doi.org/10.3390/ijms22010080
Tagliamonte MS, et al. Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements. Int J Mol Sci. 2020 Dec 23;22(1) PubMed PMID: 33374797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements. AU - Tagliamonte,Massimiliano S, AU - Abid,Nabil, AU - Borocci,Stefano, AU - Sangiovanni,Elisa, AU - Ostrov,David A, AU - Kosakovsky Pond,Sergei L, AU - Salemi,Marco, AU - Chillemi,Giovanni, AU - Mavian,Carla, Y1 - 2020/12/23/ PY - 2020/10/31/received PY - 2020/12/17/revised PY - 2020/12/18/accepted PY - 2020/12/30/entrez PY - 2020/12/31/pubmed PY - 2021/1/22/medline KW - ACE2 KW - COVID-19 KW - S glycoprotein KW - SARS-CoV-2 KW - bioinformatics KW - furin-like cleavage site KW - molecular dynamics KW - recombination JF - International journal of molecular sciences JO - Int J Mol Sci VL - 22 IS - 1 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/33374797/Multiple_Recombination_Events_and_Strong_Purifying_Selection_at_the_Origin_of_SARS_CoV_2_Spike_Glycoprotein_Increased_Correlated_Dynamic_Movements_ L2 - https://www.mdpi.com/resolver?pii=ijms22010080 DB - PRIME DP - Unbound Medicine ER -