Studying the structural dynamics of the SARS-CoV-2: comparing optimal pH

The Spike protein of SARS-CoV-2 plays a critical role in the virus’s ability to invade human cells, facilitating its entry and infection. Several Spike mutations were found in SARS-CoV-2 variants, which are related to higher transmissibility, pathogenicity, and resistance to neutralization antibodies. Understanding the structural and functional dynamics of this protein is essential as the virus continues to evolve, adjusting its adaptation mechanisms. Keeping monitoring and analyzing the virus not only increases the control, but may also improve therapeutic strategies.
Through the GISAID database, it was possible to identify the frequent SARS-CoV-2 lineages in Brazil between May 2023 and May 2024. The genomic data was extracted from patients infected with these lineages, focusing on cases reported in Brazil, highlighting a set of mutations in all proteins of the virus (https://gisaid.org) [1]. For the analysis, the data was filtered to show only the mutations in the Spike protein and a frequency count of each mutation was conducted, having eliminated those that appeared only once and selecting the top 5% most frequent mutations for further studies, resulting in a total of 40 mutations. A wild-type (WT) and apo Cryo-EM SARS-CoV-2 Spike structure with 2.90Å resolution (PDB: 6XR8) was rebuilt using CHARMM-Gui to complete the missing residues [2] and the Solution Builder was used to prepare the protein in different pHs (7.5; 8; 8.5; 9) to determine the optimal pH for subsequent studies [3].

This work is supported by CAPES (Coordination for the Improvement of Higher Education Personnel)

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