Conserved amino acids W423 and N424 in receptor-binding domain of SARS-CoV are potential targets for therapeutic monoclonal antibody.

نویسندگان

  • Chao Bian
  • Xiuqin Zhang
  • Xingfeng Cai
  • Linqi Zhang
  • Zhiwei Chen
  • Ye Zha
  • Ying Xu
  • Ke Xu
  • Wei Lu
  • Linchen Yan
  • Jianwei Yuan
  • Jiannan Feng
  • Pei Hao
  • Qidi Wang
  • Guoping Zhao
  • Gang Liu
  • Xueliang Zhu
  • Hao Shen
  • Bojian Zheng
  • Beifen Shen
  • Bing Sun
چکیده

The receptor-binding domain (RBD) on spike protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the main region interacting with the viral receptor-ACE2 and is a useful target for induction of neutralizing antibodies against SARS-CoV infection. Here we generated two monoclonal antibodies (mAbs), targeting RBD, with marked virus neutralizing activity. The mAbs recognize a new conformational epitope which consists of several discontinuous peptides (aa. 343-367, 373-390 and 411-428) and is spatially located neighboring the receptor-binding motif (RPM) region of the RBD. Importantly, W423 and N424 residues are essential for mAb recognition and are highly conserved among 107 different strains of SARS, indicating that the residues are the most critical in the epitope which is a novel potential target for therapeutic mAbs. A human-mouse chimeric antibody, based upon the original murine mAb, was also constructed and shown to possess good neutralizing activity and high affinity.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The evil role of spike in the coronaviruses: structure, function and evolution

1. Lu R, Zhao X, Li J, et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395:565–574 2. Zhou P, Tachedjian M, Wynne JW, et al (2016) Contraction of the type i IFN locus and unusual constitutive expression of IFN-α in bats. Proc Natl Acad Sci U S A 113:2696–2701 . doi: 10.1073/pnas.1518240113 3. Wu A, P...

متن کامل

Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants.

In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduce...

متن کامل

Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants

BACKGROUND Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncomp...

متن کامل

Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing

Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmA...

متن کامل

کاربری پروتیین‌های جدید در ساخت واکسن استافیلوکوکوس اورئوس

Background: Staphylococcus aureus and Staphylococcus epidermidis are major human pathogens of increasing importance due to the spread of antibiotic resistance. Novel potential targets for therapeutic antibodies are products of staphylococcal genes expressed during human infection. Previously, the secreted and surface-exposed proteins among seroreactive antigens have been discovered. Furthermore...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Virology

دوره 383 1  شماره 

صفحات  -

تاریخ انتشار 2009