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典型文献
Assessment of the binding interactions of SARS-CoV-2 spike glycoprotein variants
文献摘要:
Severe acute respiratory syndrome-associated coronavirus 2 is a major global health issue and is driving the need for new therapeutics.The surface spike protein,which plays a central role in virus infection,is currently the target for vaccines and neutralizing treatments.The emergence of novel variants with multiple mutations in the spike protein may reduce the effectiveness of neutralizing antibodies by altering the binding activity of the protein with angiotensin-converting enzyme 2(ACE2).To understand the impact of spike protein mutations on the binding interactions required for virus infection and the effectiveness of neutralizing monoclonal antibody(mAb)therapies,the binding activities of the original spike protein receptor binding domain(RBD)sequence and the reported spike protein variants were investigated using surface plasmon resonance.In addition,the interactions of the ACE2 receptor,an anti-spike mAb(mAb1),a neutralizing mAb(mAb2),the original spike RBD sequence,and mutants D614G,N501Y,N439K,Y453F,and E484K were assessed.Compared to the original RBD,the Y453F and N501Y mutants displayed a significant increase in ACE2 binding affinity,whereas D614G had a substantial reduction in binding affinity.All mAb-RBD mutant proteins displayed a reduction in binding affinities relative to the original RBD,except for the E484K-mAb1 interaction.The potential neutralizing capability of mAb1 and mAb2 was investigated.Accordingly,mAb1 failed to inhibit the ACE2-RBD interaction while mAb2 inhibited the ACE2-RBD interactions for all RBD mutants,except mutant E484K,which only dis-played partial blocking.
文献关键词:
作者姓名:
Deepa Raghu;Pamela Hamill;Arpitha Banaji;Amy McLaren;Yu-Ting Hsu
作者机构:
Product Characterization,MilliporeSigma,Rockville,MD,20850,USA;Product Characterization,MilliporeSigma,Stirling,FK9 4NF,UK;Process and Analytical Development,MilliporeSigma,St.Louis,MO,63118,USA
引用格式:
[1]Deepa Raghu;Pamela Hamill;Arpitha Banaji;Amy McLaren;Yu-Ting Hsu-.Assessment of the binding interactions of SARS-CoV-2 spike glycoprotein variants)[J].药物分析学报(英文),2022(01):58-64
A类:
mAb1,mAb2,N439K,Y453F
B类:
Assessment,binding,interactions,SARS,CoV,spike,glycoprotein,variants,Severe,acute,respiratory,syndrome,associated,coronavirus,major,global,health,issue,driving,need,new,therapeutics,surface,which,plays,central,role,infection,currently,target,vaccines,neutralizing,treatments,emergence,novel,multiple,mutations,may,reduce,effectiveness,antibodies,by,altering,activity,angiotensin,converting,enzyme,ACE2,To,understand,impact,required,monoclonal,antibody,therapies,activities,original,receptor,domain,RBD,sequence,reported,were,investigated,using,plasmon,resonance,In,addition,mutants,D614G,N501Y,E484K,assessed,Compared,displayed,significant,increase,affinity,whereas,had,substantial,reduction,All,proteins,affinities,relative,except,potential,capability,was,Accordingly,failed,while,inhibited,all,only,partial,blocking
AB值:
0.420715
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