Computers in biology and medicine · 2022
Genomic and structural mechanistic insight to reveal the differential infectivity of omicron and other variants of concern.
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Sharma Priyanka, Kumar Mukesh, Tripathi Manish Kumar, Gupta Deepali, Vishwakarma Poorvi, Das Uddipan, Kaur Punit
Аннотация
BACKGROUND: The genome of SARS-CoV-2, is mutating rapidly and continuously challenging the management and preventive measures adopted and recommended by healthcare agencies. The spike protein is the main antigenic site that binds to the host receptor hACE-2 and is recognised by antibodies. Hence, the mutations in this site were analysed to assess their role in differential infectivity of lineages having these mutations, rendering the characterisation of these lineages as variants of concern (VOC) and variants of interest (VOI).
METHODS: In this work, we examined the genome sequence of SARS-CoV-2 VOCs and their phylogenetic relationships with the other PANGOLIN lineages. The mutational landscape of WHO characterized variants was determined and mutational diversity was compared amongst the different severity groups. We then computationally studied the structural impact of the mutations in receptor binding domain of the VOCs. The binding affinity was quantitatively determined by molecular dynamics simulations and free energy calculations.
RESULTS: The mutational frequency, as well as phylogenetic distance, was maximum in the case of omicron followed by the delta variant. The maximum binding affinity was for delta variant followed by the Omicron variant. The increased binding affinity of delta strain followed by omicron as compared to other variants and wild type advocates high transmissibility and quick spread of these two variants and high severity of delta variant.
CONCLUSION: This study delivers a foundation for discovering the improved binding knacks and structural features of SARS-CoV-2 variants to plan novel therapeutics and vaccine candidates against the virus.
METHODS: In this work, we examined the genome sequence of SARS-CoV-2 VOCs and their phylogenetic relationships with the other PANGOLIN lineages. The mutational landscape of WHO characterized variants was determined and mutational diversity was compared amongst the different severity groups. We then computationally studied the structural impact of the mutations in receptor binding domain of the VOCs. The binding affinity was quantitatively determined by molecular dynamics simulations and free energy calculations.
RESULTS: The mutational frequency, as well as phylogenetic distance, was maximum in the case of omicron followed by the delta variant. The maximum binding affinity was for delta variant followed by the Omicron variant. The increased binding affinity of delta strain followed by omicron as compared to other variants and wild type advocates high transmissibility and quick spread of these two variants and high severity of delta variant.
CONCLUSION: This study delivers a foundation for discovering the improved binding knacks and structural features of SARS-CoV-2 variants to plan novel therapeutics and vaccine candidates against the virus.