2020-2025: bioinformatic analyses of the spike protein of SARS Cov-2 and its variants, structures, functions, interactions, and evolution

In 2019, a novel virus was isolated in Wuhan, China, from a patient suffering from pneumonia: the "Severe Acute Respiratory Syndrome coronavirus 2" (SARS-CoV-2). It was initially a relatively weak pathogen, lethal only in the elderly and people with comorbidities. However, in 2020, the more infectious and pathogenic variant D614G of the Spike protein spread in Europe. The pandemic caused >750 million cases and 7 million deaths1, bringing the scientific community to analyse emerging variants, with the aim of both developing mAbs, antivirals and vaccines, and predicting the effects of mutations on infectivity, immune evasion and pathogenicity. An interesting focus that has concerned more recent publications analyses the long-term effects of SARS-CoV-2 infection, like PASC syndrome and brain fog, which suggests a possible evolution of the binding targets of the virus. Since in 2020 bioinformatic techniques for studying mutations and their effects on protein structures and receptor binding capabilities were already well developed, many research teams undertook in silico studies of protein variants, focusing on the S protein, which mediates the infection through the bond with receptors such as ACE-2 and neuropilin. This thesis presents a review of the scientific literature published in this field from 2020 to 2025.