Coronavirus disease 19, or COVID-19, is an infection associated with an unprecedented worldwide pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has led to more than 215 million infected people and more than 4.5 million deaths worldwide. SARS-CoV-2 cell infection is initiated by a densely glycosylated spike (S) protein, a fusion protein, binding human angiotensin converting enzyme 2 (hACE2), that acts as the functional receptor through the receptor binding domain (RBD). In this article, the interaction of hACE2 with the RBD and how fusion is initiated after recognition are explored, as well as how mutations influence infectivity and immune response. Thus, we focused on all structures available in the Protein Data Bank for the interaction between SARS-CoV-2 S protein and hACE2. Specifically, the Delta variant carries particular mutations associated with increased viral fitness through decreased antibody binding, increased RBD affinity and altered protein dynamics. Combining both existing mutations and mutagenesis studies, new potential SARS-CoV-2 variants, harboring advantageous S protein mutations, may be predicted. These include mutations S13I and W152C, decreasing antibody binding, N460K, increasing RDB affinity, or Q498R, positively affecting both properties.
【저자키워드】 SARS-CoV-2, Spike protein, hACE2, protein structures, 【초록키워드】 COVID-19, coronavirus disease, severe acute respiratory syndrome coronavirus 2, Structure, coronavirus, immune response, Mutation, S protein, mutations, Infection, severe acute respiratory syndrome Coronavirus, delta variant, angiotensin converting enzyme, coronavirus 2, hACE2, Receptor binding domain, Protein, Antibody binding, Viral, SARS-CoV-2 variants, RBD, death, receptor, fusion protein, coronavirus disease 19, respiratory, binding, SARS-CoV-2 S protein, Mutagenesis, Interaction, angiotensin, Protein Data Bank, Recognition, acute respiratory syndrome coronavirus, enzyme, worldwide pandemic, human angiotensin converting enzyme 2, viral fitness, RBD affinity, SARS-CoV-2 cell infection, predicted, caused, include, functional, the RBD, initiated, glycosylated, affecting, 【제목키워드】 Structure, Infectivity, emergence, response,