Abstract
After two years since the outbreak, the COVID-19 pandemic remains a global public health emergency. SARS-CoV-2 variants with substitutions on the spike (S) protein emerge increasing the risk of immune evasion and cross-species transmission. Here, we analyzed the evolution of the S protein as recorded in 276,712 samples collected before the start of vaccination efforts. Our analysis shows that most variants destabilize the S protein trimer, increase its conformational heterogeneity and improve the odds of the recognition by the host cell receptor. Most frequent substitutions promote overall hydrophobicity by replacing charged amino acids, reducing stabilizing local interactions in the unbound S protein trimer. Moreover, our results identify “forbidden” regions that rarely show any sequence variation, and which are related to conformational changes occurring upon fusion. These results are significant for understanding the structure and function of SARS-CoV-2 related proteins which is a critical step in vaccine development and epidemiological surveillance.
Keywords: ACE2; COVID-19; HADDOCK; S protein; protein–protein interactions.
【저자키워드】 COVID-19, ACE2, S protein, protein–protein interactions., HADDOCK, 【초록키워드】 Evolution, SARS-CoV-2, Vaccine development, vaccination, S protein, COVID-19 pandemic, variant, SARS-CoV-2 variant, risk, heterogeneity, Protein, immune evasion, Region, Surveillance, SARS-CoV-2 variants, outbreak, substitutions, amino acids, hydrophobicity, epidemiological, epidemiological surveillance, fusion, Critical, Analysis, Cross-species transmission, HADDOCK, conformational change, protein–protein interactions, host cell, Recognition, global public health, Substitution, trimer, host cell receptor, global public health emergency, conformational changes, sequence variation, MOST, local interactions, IMPROVE, analyzed, identify, collected, reducing, promote, conformational, the S protein, recorded, replacing, local interaction, 【제목키워드】 SARS-CoV-2, spike, Selection,