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Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity

Our take —

The origins of SARS-CoV-2 are still somewhat unclear, but it likely has been present in the USA for longer than it was originally thought due to the authors’ data showing two potential origin sites. Additionally, it likely mutated into its current form before it was present in bats. SARS-CoV-2 does not mutate as fast as SARS, which is a relief due to the fact that it has the potential for many mutations since it is a single-stranded RNA virus. Despite this, mutations in the S-protein/RBD specific to ACE2 may begin to appear – one has been detected in a sequence from India – and this could have challenging implications for vaccine development.

Study design

Other

Study population and setting

This study utilized 106 sequences of the SARS-CoV-2 genome from 12 countries that were available on National Center for Biotechnology Information (NCBI) as of March 24, 2020. 54 sequences from the USA, 35 from China, 3 from Spain, 2 from Brazil, and one sequence each from Australia, Finland, India, Italy, Nepal, South Korea, and Sweden were selected. The genomes were annotated and genes were analyzed for sequence conservation. A phylogenetic tree was constructed to assess the evolutionary rate of the virus. Additionally, structural analyses were performed on the SARS-CoV-2 S-protein in complex with the human ACE2 receptor.

Summary of Main Findings

This study utilized 106 sequences of the SARS-CoV-2 genome from 12 countries that were available on NCBI as of March 24, 2020. 54 sequences from the USA, 35 from China, 3 from Spain, 2 from Brazil, and one sequence each from Australia, Finland, India, Italy, Nepal, South Korea, and Sweden were selected. The genomes were annotated and genes were analyzed for sequence conservation. A phylogenetic tree was constructed to assess the evolutionary rate of the virus. Additionally, structural analyses were performed on the SARS-CoV-2 S-protein in complex with the human ACE2 receptor.

Study Strengths

This study covers a wide array of topic ranging from sequence phylogeny, ecology and spillover, protein structure, binding affinity, and potential implications for vaccine development. It is a fairly comprehensive analysis of SARS-CoV-2 genomes that were currently available on NCBI at the time the research was performed.

Limitations

All molecular clones carry the limitation that they are only representative of the original virus from which they were derived. As the SARS-CoV-2 virus is still new in the population and still rapidly circulating, it remains to be seen if major major mutations will arise in the genome that will need to be represented in any molecular clones used for further study.

Value added

This article brings to light that the origin of SARS-CoV-2 may be more complex than was previously thought, and emphasizes potential roadblocks in the future for vaccine development for this virus.