Volume 31, No 6, Jun 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 6, June 2021: 720-722

LETTERS TO THE EDITOR

The basis of a more contagious 501Y.V1 variant of SARS-CoV-2

Haolin Liu^1,2,* , Qianqian Zhang³ , Pengcheng Wei^1,2 , Zhongzhou Chen³ , Katja Aviszus^1,2 , John Yang⁴ , Walter Downing⁵ , Chengyu Jiang⁶ , Bo Liang⁷ , Lyndon Reynoso⁸ , Gregory P. Downey⁴ , Stephen K. Frankel⁴ , John Kappler^1,2 , Philippa Marrack^1,2,* , Gongyi Zhang^1,2,*

¹Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA
²Department of Immunology and Microbiology, School of Medicine, Anschutz Medical Center, University of Colorado, Aurora, CO 80216, USA
³State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agriculture University, Beijing 100193, China
⁴Department of Medicine, National Jewish Health, Denver, CO 80206, USA
⁵Department of Nursing, National Jewish Health, Denver, CO 80206, USA
⁶Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing 100005, China
⁷Department of Biochemistry, Emory University of School of Medicine, Atlanta, GA 30322, USA
⁸Department of Pharmacy, National Jewish Health, Denver, CO 80206, USA
These authors contributed equally: Haolin Liu, Qianqian Zhang Correspondence: Haolin Liu(Liuh@NJhealth.org)Philippa Marrack(Marrackp@NJhealth.org)Gongyi Zhang(Zhangg@NJhealth.org)

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.

https://doi.org/10.1038/s41422-021-00496-8

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