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您的检索式：作者名="Gregory PDowney"
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| 1 | The basis of a more contagious 501Y.V1 variant of SARS-CoV-2显示文摘Dear Editor,The SARS-CoV-2 virus has infected over one hundred million people(COVID-19 patients)and caused more than two million deaths to date.The number of infected people continues to grow quickly,emphasizing the need for rapid use of effective vaccines.Although two mRNA vaccines based on Spike protein(produced by Pfizer-BioNTech and MODERNA)have been approved for emergency use in the US,1,2 the increasing Spike variants that have appeared around the world raise concerns about the continued efficacy of the vaccines.3 Monoclonal antibodies,developed by Regeneron and Eli Lilly,specifically targeting the native form of Spike have been approved by the FDA for emergency use.4,5 An N501Y variant(Y501)of the Spike protein of SARS-CoV-2(B.1.1.7,20I/501Y.V1),first emerged in UK and has now spread to the rest of the world.This variant appears to be much more contagious than the original N501 version.3 Furthermore,Y501 mutation is also found in a variant(B.1.351,20H/501Y.V2)from South Africa and a variant(P1,20J/501Y.V3)from Brazil.3 Unfortunately,this mutation is located at the interaction surface between the RBD and human Angiotensin Converting Enzyme 2(ACE2).6 Thus,the Y501 variation present in B.1.1.7,20I/501Y.V1 might affect the binding ability of the RBD to bind ACE2.We therefore compared the binding affinity of N501 and Y501 RBD for ACE2,uncovering that the affinity for ACE2 of the Y501-RBD was~10 fold higher than that of the N501 version.This may account,at least in part,for the greater infectivity of SARS-CoV-2 with this mutation.Structural modeling data showed that Y501-RBD can form an additional aromatic ring–ring interaction and an additional hydrogen bond with ACE2 by comparison with the RBD of the wild type.In spite of this,sera from individuals immunized with the Pfizer-BioNTech vaccine still efficiently block ACE2 binding to Y501-RBD.Furthermore,Bamlanivimab,the recently FDA approved therapeutic antibody drug for treatment of COVID-19 patients4 still binds the variant Y501-RBD as efficiently as it binds the N501-RBD,giving hope that treatment with the existing monoclonal antibodies may still help COVID-19 patients. | Haolin Liu Qianqian Zhang Pengcheng Wei Zhongzhou Chen Katja Aviszus John Yang Walter Downing Chengyu Jiang Bo Liang Lyndon Reynoso Gregory PDowney Stephen KFrankel John Kappler Philippa Marrack Gongyi Zhang | 2021 | Cell Research2021，31，6： | 1 |
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