In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics
New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive b...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/11/2461 |
| _version_ | 1797466237876305920 |
|---|---|
| author | Dhruv Chauhan Nikhil Chakravarty Arjit Vijey Jeyachandran Akshaya Jayakarunakaran Sanjeev Sinha Rakesh Mishra Vaithilingaraja Arumugaswami Arunachalam Ramaiah |
| author_facet | Dhruv Chauhan Nikhil Chakravarty Arjit Vijey Jeyachandran Akshaya Jayakarunakaran Sanjeev Sinha Rakesh Mishra Vaithilingaraja Arumugaswami Arunachalam Ramaiah |
| author_sort | Dhruv Chauhan |
| collection | DOAJ |
| description | New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron’s spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome. |
| first_indexed | 2024-03-09T18:33:59Z |
| format | Article |
| id | doaj.art-31196d8ceb1b4ac8a476be4925de9f6b |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T18:33:59Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-31196d8ceb1b4ac8a476be4925de9f6b2023-11-24T07:17:35ZengMDPI AGViruses1999-49152022-11-011411246110.3390/v14112461In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral TherapeuticsDhruv Chauhan0Nikhil Chakravarty1Arjit Vijey Jeyachandran2Akshaya Jayakarunakaran3Sanjeev Sinha4Rakesh Mishra5Vaithilingaraja Arumugaswami6Arunachalam Ramaiah7Tata Institute for Genetics and Society, Centre at inStem, Bangalore 560065, IndiaDepartment of Epidemiology, University of California, Los Angeles, CA 90095, USADepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USADepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USAAll India Institute of Medical Sciences, New Delhi 110029, IndiaTata Institute for Genetics and Society, Centre at inStem, Bangalore 560065, IndiaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USATata Institute for Genetics and Society, Centre at inStem, Bangalore 560065, IndiaNew variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron’s spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome.https://www.mdpi.com/1999-4915/14/11/2461SARS-CoV-2OmicronCOVID-19evolutionreceptor binding domainT-cell epitope |
| spellingShingle | Dhruv Chauhan Nikhil Chakravarty Arjit Vijey Jeyachandran Akshaya Jayakarunakaran Sanjeev Sinha Rakesh Mishra Vaithilingaraja Arumugaswami Arunachalam Ramaiah In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics Viruses SARS-CoV-2 Omicron COVID-19 evolution receptor binding domain T-cell epitope |
| title | In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics |
| title_full | In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics |
| title_fullStr | In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics |
| title_full_unstemmed | In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics |
| title_short | In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics |
| title_sort | in silico genome analysis reveals the evolution and potential impact of sars cov 2 omicron structural changes on host immune evasion and antiviral therapeutics |
| topic | SARS-CoV-2 Omicron COVID-19 evolution receptor binding domain T-cell epitope |
| url | https://www.mdpi.com/1999-4915/14/11/2461 |
| work_keys_str_mv | AT dhruvchauhan insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics AT nikhilchakravarty insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics AT arjitvijeyjeyachandran insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics AT akshayajayakarunakaran insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics AT sanjeevsinha insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics AT rakeshmishra insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics AT vaithilingarajaarumugaswami insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics AT arunachalamramaiah insilicogenomeanalysisrevealstheevolutionandpotentialimpactofsarscov2omicronstructuralchangesonhostimmuneevasionandantiviraltherapeutics |