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

Massimiliano S Tagliamonte1,2 Nabil Abid3,4 Stefano Borocci5,6 Elisa Sangiovanni5 David A Ostrov2 Sergei L Kosakovsky Pond7 Marco Salemi1,2 Giovanni Chillemi5,8 Carla Mavian1,2
Affiliations 8 institutions
  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.
PMID 33374797 2020 Int J Mol Sci eng epublish
PubMed DOI Browse context

Article

Publication summary

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.

ACE2 bioinformatics COVID-19 furin-like cleavage site molecular dynamics recombination S glycoprotein SARS-CoV-2 Recombination, Genetic Amino Acid Sequence Animals Chiroptera Coronavirus Evolution, Molecular Host Specificity Humans Molecular Dynamics Simulation Pangolins

Structured evidence records

Evidence records

5 total
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.70
Key finding

SARS-CoV-2 spike gene evolution reflects inter-species coronavirus transmission between bat and pangolin hosts.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The first movement involves the receptor binding domain with the N-terminal domain and is maintained across human, bat and pangolin coronaviruses... negative selection preserved its inter-domain structure throughout evolution in different hosts and inter-species transmissions.

Method
evolutionary analysis; molecular dynamics simulation; phylogenetic analysis
Study design
phylogenetic analysis
Transmission direction
animal-to-animal
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.95
Key finding

Genomic and phylogenetic analyses indicated that the SARS-CoV-2 spike gene evolved through multiple recombination events and is under purifying selection conserving structural elements among human, bat, and pangolin coronaviruses.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

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. ... These movements are maintained across human, bat and pangolin coronaviruses.

Genes or proteins
spike glycoprotein
Analysis methods
evolutionary analysis; recombination analysis; purifying selection analysis; phylogenetic analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.80
Key finding

The SARS-CoV-2 spike glycoprotein shows molecular adaptation through recombination and purifying selection that preserved structural domains essential for host cell binding across human, bat, and pangolin coronaviruses.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

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. These movements, essential for host cell binding, are maintained by hinges conserved across human, bat, and pangolin coronaviruses glycoproteins.

Genes or proteins
spike glycoprotein
Receptors
ACE2
Mechanism types
receptor_binding; host_range_adaptation; structural_conservation
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.60
Key finding

SARS-CoV-2 spike glycoprotein maintains conserved receptor binding domain movements related to ACE2-mediated host cell binding in human, bat, and pangolin coronaviruses.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Keywords include "ACE2" alongside analysis of "spike glycoprotein" and the abstract states that dynamic movements involving the receptor binding domain are maintained across human, bat and pangolin coronaviruses, essential for host cell binding.

Method
molecular dynamics simulation; bioinformatics
Receptors
ACE2
Recombination Or Reassortment 1 records
Recombination Or Reassortment Extraction confidence 1.00
Key finding

The SARS-CoV-2 spike gene evolved through multiple recombination events that generated a mosaic genome structure influencing inter-species conservation and dynamics.

Host
Not specified
Location
Not specified
Supporting text

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.

Event type
recombination
Genes or segments
spike