Effect of An 84-bp Deletion of the Receptor-Binding Domain on the ACE2 Binding Affinity of the SARS-CoV-2 Spike Protein: An In Silico Analysis

SARS-CoV-2 is a recently emerged, novel human coronavirus responsible for the currently ongoing COVID-19 pandemic. Recombination is a well-known evolutionary strategy of coronaviruses, which may frequently result in significant genetic alterations, such as deletions throughout the genome. In this study we identified a co-infection with two genetically different SARS-CoV-2 viruses within a single patient sample via amplicon-based next generation sequencing in Hungary. The recessive strain contained an 84 base pair deletion in the receptor binding domain of the Spike protein gene and was found to be gradually displaced by a dominant non-deleterious variant over-time. We have identified the region of the RBD that is affected by the mutation, created homology models of the RBD Delta 84 mutant, and based on the available experimental data and calculations, we propose that the mutation has a deteriorating effect on the binding of RBD to the ACE2 receptor, which results in the negative selection of this variant. Extending the sequencing capacity toward the discovery of emerging recombinant or deleterious strains may facilitate the early recognition of novel strains with altered phenotypic attributes and understand key elements of Spike protein evolution. Such studies may greatly contribute to future therapeutic research and general understanding of genomic processes of the virus.

Automated summary

In this study, a co-infection of two genetically different SARS-CoV-2 viruses within a single patient was identified in Hungary, with one strain containing an 84-base pair deletion in the Spike protein gene. The recessive variant was gradually replaced by a dominant non-deleterious variant over time. The mutation in the receptor binding domain of the Spike protein gene was suggested to have a negative effect on the binding of RBD to the ACE2 receptor, leading to the negative selection of the variant.