The Key Site Variation and Immune Challenges in SARS-CoV-2 Evolution

Coronavirus disease 2019 (COVID-19) is a worldwide public health and economic threat, and virus variation amplifies the difficulty in epidemic prevention and control. The structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been studied extensively and is now well defined. The S protein is the most distinguishing feature in terms of infection and immunity, mediating virus entrance and inducing neutralizing antibodies. The S protein and its essential components are also the most promising target to develop vaccines and antibody-based drugs. Therefore, the key site mutation in the S gene is of high interest. Among them, RBD, NTD, and furin cleavage sites are the most mutable regions with the most mutation sites and the most serious consequences for SARS-CoV-2 biological characteristics, including infectivity, pathogenicity, natural immunity, vaccine efficacy, and antibody therapeutics. We are also aware that this outbreak may not be the last. Therefore, in this narrative review, we summarized viral variation and prevalence condition, discussed specific amino acid replacement and associated immune challenges and attempted to sum up some prevention and control strategies by reviewing the literature on previously published research about SARS-CoV-2 variation to assist in clarifying the mutation pathway and consequences of SARS-CoV-2 for developing countermeasures against such viruses as soon as possible.