The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the subsequent COVID-19 pandemic have visited a terrible cost on the world in the forms of disease, death, and economic turmoil. The rapid development and deployment of extremely effective vaccines against SARS-CoV-2 have seemingly brought within reach the end of the pandemic. However, the virus has acquired mutations. and emerging variants of concern are more infectious and reduce the efficacy of existing vaccines. Although promising efforts to combat these variants are underway, the evolutionary pressures leading to these variants are poorly understood. To that end, here we have studied the effects on the structure and function of the SARS-CoV-2 spike glycoprotein receptor-binding domain of three amino-acid substitutions found in several variants of concern, including alpha (B.1.1.7), beta (B.1.351), and gamma (P.1). We found that these substitutions alter the receptor-binding domain structure, stability, and ability to bind to angiotensin converting enzyme 2, in such a way as to possibly have opposing and compensatory effects. These findings provide new insights into how these variants of concern may have been selected for infectivity while maintaining the structure and stability of the receptor binding domain.
【저자키워드】 RBD, receptor-binding domain, ACE2, angiotensin converting enzyme 2, bis-ANS, 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid, HRP-RBD, horseradish preroxidase-labeled RBD, SARS-CoV-2, severe acute respiratory syndrome-related coronavirus 2, VOC, variants of concern, 【초록키워드】 SARS-CoV-2, Efficacy, coronavirus, pandemic, Vaccines, B.1.351, COVID-19 pandemic, angiotensin converting enzyme 2, mutations, variant, spike glycoprotein, variants of concern, virus, angiotensin converting enzyme, Receptor binding domain, Severe acute respiratory syndrome, stability, B.1.1.7, P.1, death, Alpha, Beta, Severe acute respiratory syndrome-related coronavirus, respiratory, disease, angiotensin, acute respiratory syndrome, enzyme, domain, effort, Substitution, several variants, amino-acid, forms, Effect, Alter, Effects, selected, subsequent, form, the receptor-binding domain, effective vaccine, reduce, several variant, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, stability, Beta variant, Substitution, Alter,