Abstract
The rapid spread of SARS-CoV-2 has caused the COVID-19 pandemic, resulting in the collapse of medical care systems and economic depression worldwide. To combat COVID-19, neutralizing antibodies have been investigated and developed. However, the evolutions (mutations) of the receptor-binding domain (RBD) of SARS-CoV-2 enable escape from neutralization by these antibodies, further impairing recognition by the human immune system. Thus, it is critical to investigate and predict the putative mutations of RBD that escape neutralizing immune responses. Here, we employed computational analyses to comprehensively investigate the mutational effects of RBD on binding to neutralizing antibodies and angiotensin-converting enzyme 2 (ACE2) and demonstrated that the RBD residues K417, L452, L455, F456, E484, G485, F486, F490, Q493, and S494 were consistent with clinically emerging variants or experimental observations of attenuated neutralizations. We also revealed common hotspots, Y449, L455, and Y489, that exerted comparable destabilizing effects on binding to both ACE2 and neutralizing antibodies. Our results provide valuable information on the putative effects of RBD variants on interactions with neutralizing antibodies. These findings provide insights into possible evolutionary hotspots that can escape recognition by these antibodies. In addition, our study results will benefit the development and design of vaccines and antibodies to combat the newly emerging variants of SARS-CoV-2.
Highlights
SARS-CoV-2, which causes viral pneumonia in humans, is the cause of COVID-19 (Lai et al, 2020)
The results revealed that mutations at Y449, N450, L452, E484, Y489, F490, P491, L492, Q493, and S494 were mostly not favorable for binding stability (Figure 2B and Table 1)
We found that receptor-binding domain (RBD) variants mutated at R403, K417, G447, N448, Y449, N450, L452, Y453, L455, F456, E484, G485, F486, Y489, F490, Q493, S494, Y495, and G496 were unfavorable to binding with antibodies (Table 1)
Summary
SARS-CoV-2, which causes viral pneumonia in humans, is the cause of COVID-19 (Lai et al, 2020). The virus exhibits crown-like morphology (“corona”) and is named coronavirus (Gui et al, 2017). The World Health Organization declared COVID-19 as a pandemic. In April 2021, there were 142.5 million confirmed cases of COVID-19, including 3,043,707 deaths (daily online worldwide data about COVID-191). Common symptoms of SARS-CoV-2 infection include diarrhea, dry cough, fever, nasal congestion, respiratory problems, and sore throat (Baj et al, 2020). Kidney failure, severe acute respiratory syndrome, and pneumonia may ensue, eventually leading to death (Lai et al, 2020)
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