Taking stock of the mutations in human SARS-CoV-2 spike proteins: From early days to nearly the end of COVID-19 pandemic

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causative agent of the coronavirus disease-2019 (COVID-19) has resulted in several deaths and severe economic losses throughout the world. The spike protein in the virus binds to the human ACE-2 receptor in order to mediate virus-host interactions required for the viral transmission. Since first report of the SARS-CoV-2 sequence during December 2019 from patient infected with the virus in Wuhan, China, the virus has undergone rapid changes leading to mutations comprising substitutions, deletions and insertions in the sequence resulting in several variants of the virus that were more virulent and transmissible or less virulent but highly transmissible. The timely intervention with COVID-19 vaccines proved to be effective in controlling the number of infections. However, rapid mutations in the virus led to the lowering of vaccine efficacies being administered to people. In May 2023, the World Health Organization declared COVID-19 was not a public health emergency of international concern anymore. In order to take stock of mutations in the virus from early days to nearly end of COVID-19 pandemic, sequence analyses of the SARS-CoV-2 spike proteins available in the NCBI Virus database was carried out. The mutations and invariant residues in the SARS-CoV-2 spike protein sequences relative to the reference sequence were analysed. The location of the invariant residues and residues at interface of the protein chains in the spike protein trimer complex structure were examined. A total of 111,298 non-redundant SARS-CoV-2 spike protein sequences representing 2,345,585 spike proteins in the NCBI Virus database showed mutations at 1252 of the 1273 positions in the amino acid sequence. The mutations represented 6129 different mutation types in the sequences analysed. Besides, some sequences also contained insertion mutations. The SARS-CoV-2 spike protein sequences represented 1435 lineages. In addition, several spike protein sequences with mutations whose lineages were either ‘not classified’ or were ‘unclassifiable’ indicated the virus could still be evolving.