Evolutionary and codon usage preference insights into spike glycoprotein of SARS-CoV-2.

Yashpal Singh Malik1 Mohd Ikram Ansari2 Jobin Jose Kattoor3 Rahul Kaushik4 Shubhankar Sircar5 Anbazhagan Subbaiyan6 Ruchi Tiwari7 Kuldeep Dhama8 Souvik Ghosh9 Shailly Tomar10 Kam Y J Zhang11
Affiliations 11 institutions
  1. College of Animal Biotechnology, GADVASU, Ludhiana.
  2. Aligarh Muslim University India.
  3. ICAR-Indian Veterinary Research Institute, India.
  4. Laboratory for Structural Bioinformatics, RIKEN Center for Biosystems Dynamics Research, Japan.
  5. Integral University, India.
  6. ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India.
  7. Department of Vet erinary Microbiology, DUVASU, Mathura, India.
  8. Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India.
  9. Health Center for Zoonoses and Tropical Veterinary Medicine, Basseterre, St. Kitts, West Indies.
  10. Department of Biotechnology, IIT, Roorkee, India.
  11. Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, Japan.

Abstract

Interaction of SARS-CoV-2 spike glycoprotein with the ACE2 cell receptor is very crucial for virus attachment to human cells. Selected mutations in SARS-CoV-2 S-protein are reported to strengthen its binding affinity to mammalian ACE2. The N501T mutation in SARS-CoV-2-CTD furnishes better support to hotspot 353 in comparison with SARS-CoV and shows higher affinity for receptor binding. Recombination analysis exhibited higher recombination events in SARS-CoV-2 strains, irrespective of their geographical origin or hosts. Investigation further supports a common origin among SARS-CoV-2 and its predecessors, SARS-CoV and bat-SARS-like-CoV. The recombination events suggest a constant exchange of genetic material among the co-infecting viruses in possible reservoirs and human hosts before SARS-CoV-2 emerged. Furthermore, a comprehensive analysis of codon usage bias (CUB) in SARS-CoV-2 revealed significant CUB among the S-genes of different beta-coronaviruses governed majorly by natural selection and mutation pressure. Various indices of codon usage of S-genes helped in quantifying its adaptability in other animal hosts. These findings might help in identifying potential experimental animal models for investigating pathogenicity for drugs and vaccine development experiments.

Supporting text Virus Host Location
ACE2 receptor 4 codon usage analysis 1 COVID-19 467 recombination 40 S-protein 1 SARS-CoV-2 550 Biological Evolution 28 Codon Usage 6 Angiotensin-Converting Enzyme 2 177 Animals 1948 Humans 1440 Models, Animal 6 Mutation 209 RNA, Transfer 1 SARS-CoV-2 453 Spike Glycoprotein, Coronavirus 274 spike protein, SARS-CoV-2 157

Evidence records

3 total
Functional Mechanism
1 records · 1 evidence types
Evidence type
1 records
OVE4407
Key finding

The N501T mutation in the SARS-CoV-2 spike CTD enhances affinity for the ACE2 receptor by improving contact with hotspot 353 compared to SARS-CoV.

Virus
Host
Not specified
Location
Not specified
Supporting text

The N501T mutation in SARS-CoV-2-CTD furnishes better support to hotspot 353 in comparison with SARS-CoV and shows higher affinity for receptor binding.

Genes or proteins
spike | CTD
Receptors
ACE2
Mutations
N501T
Mechanism types
receptor binding | receptor usage
Genomic Evolution
2 records · 2 evidence types
Evidence type
1 records
OVE4409
Key finding

Recombination analysis indicated frequent recombination events among SARS-CoV-2 strains, suggesting exchange of genetic material with SARS-CoV and bat-SARS-like-CoV before emergence.

Virus
Host
Not specified
Location
Not specified
Supporting text

Recombination analysis exhibited higher recombination events in SARS-CoV-2 strains, irrespective of their geographical origin or hosts. Investigation further supports a common origin among SARS-CoV-2 and its predecessors, SARS-CoV and bat-SARS-like-CoV. The recombination events suggest a constant exchange of genetic material among the co-infecting viruses in possible reservoirs and human hosts before SARS-CoV-2 emerged.

Event type
recombination
Genes or segments
spike glycoprotein | S gene
Evidence type
1 records
OVE4410
Key finding

Phylogenetic analysis supports a common evolutionary origin among SARS-CoV-2, SARS-CoV, and bat-SARS-like-CoV.

Virus
Host
Location
Not specified
Supporting text

Investigation further supports a common origin among SARS-CoV-2 and its predecessors, SARS-CoV and bat-SARS-like-CoV.

Analysis methods
phylogenetic analysis