SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)has evolved many variants with stronger infectivity and immune evasion than the original strain,including Alpha,Beta,Gamma,Delta,Epsilon,Kappa,lota,Lambda,and...SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)has evolved many variants with stronger infectivity and immune evasion than the original strain,including Alpha,Beta,Gamma,Delta,Epsilon,Kappa,lota,Lambda,and 21H strains.Amino acid mutations are enriched in the spike protein of SARS CoV-2.which plays a crucial role in cell infetion.However,the impact of these mutations on protein structure and function is unclear.Understanding the pathophysiology and pandemic feaures of these SARS-CoV-2 variants requires knowledge of the spike protein structures.Here,we obtained the spike protein structures of 10 main globally endemic SARS CoV-2 strains using AlphaFold2.The clustering analysis based on structural similarity revealed the unique features of the mainly pandemic SARS CoV-2 Delta variants.indicating that structural clusters can reflect the current characteristics of the epidemic more accurately than those based on the protein sequence.The analysis of the binding afinities of ACE2-RBD,antibody-NTD,and antibody-RBD complexes in the different variants revealed that the recognition of antibodies against SI NTD and RBD was decreased in the variants,especally the Delta variant compared with the original strain,which may induce the immune evasion of SARS-CoV-2 variants.Furthermore,by virtual screening the ZINC database against a high-accuracy predicted structure of Delta spike protein and experimental validation,we identified multiple compounds that target S1 NTD and RBD,which might contribute towards the development of clinical anti-SARS-CoV-2 medicines.Our findings provided a basic foundation for future in vitro and in vivo investigations that might speed up the development of potential therapies for the SARS-CoV-2 va riants.展开更多
基金supported by the Shanghai Municipal Science and_Technology Major Project(2017SHZDZX01)NaturalScienceFoundationof,China(32070679,U1804284,and 81871055)+2 种基金the National Key R&D Program.of China(2019YFA0905400,2017YFC0908105,and 2021YFC2702103)Taishan Scholar Program of Shandong Province(tsqn201812153)and Natural Science Foundation of Shandong Province(ZR2019YQ14).
文摘SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)has evolved many variants with stronger infectivity and immune evasion than the original strain,including Alpha,Beta,Gamma,Delta,Epsilon,Kappa,lota,Lambda,and 21H strains.Amino acid mutations are enriched in the spike protein of SARS CoV-2.which plays a crucial role in cell infetion.However,the impact of these mutations on protein structure and function is unclear.Understanding the pathophysiology and pandemic feaures of these SARS-CoV-2 variants requires knowledge of the spike protein structures.Here,we obtained the spike protein structures of 10 main globally endemic SARS CoV-2 strains using AlphaFold2.The clustering analysis based on structural similarity revealed the unique features of the mainly pandemic SARS CoV-2 Delta variants.indicating that structural clusters can reflect the current characteristics of the epidemic more accurately than those based on the protein sequence.The analysis of the binding afinities of ACE2-RBD,antibody-NTD,and antibody-RBD complexes in the different variants revealed that the recognition of antibodies against SI NTD and RBD was decreased in the variants,especally the Delta variant compared with the original strain,which may induce the immune evasion of SARS-CoV-2 variants.Furthermore,by virtual screening the ZINC database against a high-accuracy predicted structure of Delta spike protein and experimental validation,we identified multiple compounds that target S1 NTD and RBD,which might contribute towards the development of clinical anti-SARS-CoV-2 medicines.Our findings provided a basic foundation for future in vitro and in vivo investigations that might speed up the development of potential therapies for the SARS-CoV-2 va riants.
