Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements
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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-12-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/1/80 |
id |
doaj-43548afe961e4152ac73c682d5e39333 |
---|---|
record_format |
Article |
spelling |
doaj-43548afe961e4152ac73c682d5e393332020-12-24T00:05:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122808010.3390/ijms22010080Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic MovementsMassimiliano S. Tagliamonte0Nabil Abid1Stefano Borocci2Elisa Sangiovanni3David A. Ostrov4Sergei L. Kosakovsky Pond5Marco Salemi6Giovanni Chillemi7Carla Mavian8Emerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USALaboratory of Transmissible Diseases and Biological Active Substances LR99ES27, Faculty of Pharmacy, University of Monastir, Rue Ibn Sina, 5000 Monastir, TunisiaDepartment for Innovation in Biological, Agro-food and Forest Systems (DIBAF), University of Tuscia, via S. Camillo de Lellis s.n.c., 01100 Viterbo, ItalyDepartment for Innovation in Biological, Agro-food and Forest Systems (DIBAF), University of Tuscia, via S. Camillo de Lellis s.n.c., 01100 Viterbo, ItalyDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Biology, Temple University, Philadelphia, PA 19122, USAEmerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USADepartment for Innovation in Biological, Agro-food and Forest Systems (DIBAF), University of Tuscia, via S. Camillo de Lellis s.n.c., 01100 Viterbo, ItalyEmerging Pathogen Institute, University of Florida, Gainesville, FL 32608, USAOur 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 <i>N</i>-terminal domain and the <i>C</i>-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 <i>C</i>-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 <i>N</i>-terminal domain and <i>C</i>-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.https://www.mdpi.com/1422-0067/22/1/80SARS-CoV-2COVID-19recombinationfurin-like cleavage siteACE2S glycoprotein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Massimiliano S. Tagliamonte Nabil Abid Stefano Borocci Elisa Sangiovanni David A. Ostrov Sergei L. Kosakovsky Pond Marco Salemi Giovanni Chillemi Carla Mavian |
spellingShingle |
Massimiliano S. Tagliamonte Nabil Abid Stefano Borocci Elisa Sangiovanni David A. Ostrov Sergei L. Kosakovsky Pond Marco Salemi Giovanni Chillemi Carla Mavian 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 SARS-CoV-2 COVID-19 recombination furin-like cleavage site ACE2 S glycoprotein |
author_facet |
Massimiliano S. Tagliamonte Nabil Abid Stefano Borocci Elisa Sangiovanni David A. Ostrov Sergei L. Kosakovsky Pond Marco Salemi Giovanni Chillemi Carla Mavian |
author_sort |
Massimiliano S. Tagliamonte |
title |
Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements |
title_short |
Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements |
title_full |
Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements |
title_fullStr |
Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements |
title_full_unstemmed |
Multiple Recombination Events and Strong Purifying Selection at the Origin of SARS-CoV-2 Spike Glycoprotein Increased Correlated Dynamic Movements |
title_sort |
multiple recombination events and strong purifying selection at the origin of sars-cov-2 spike glycoprotein increased correlated dynamic movements |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-12-01 |
description |
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 <i>N</i>-terminal domain and the <i>C</i>-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 <i>C</i>-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 <i>N</i>-terminal domain and <i>C</i>-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. |
topic |
SARS-CoV-2 COVID-19 recombination furin-like cleavage site ACE2 S glycoprotein |
url |
https://www.mdpi.com/1422-0067/22/1/80 |
work_keys_str_mv |
AT massimilianostagliamonte multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT nabilabid multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT stefanoborocci multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT elisasangiovanni multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT davidaostrov multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT sergeilkosakovskypond multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT marcosalemi multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT giovannichillemi multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements AT carlamavian multiplerecombinationeventsandstrongpurifyingselectionattheoriginofsarscov2spikeglycoproteinincreasedcorrelateddynamicmovements |
_version_ |
1724372192494354432 |