scholarly journals A human monoclonal antibody blocking SARS-CoV-2 infection

2020 ◽  
Author(s):  
Chunyan Wang ◽  
Wentao Li ◽  
Dubravka Drabek ◽  
Nisreen M.A. Okba ◽  
Rien van Haperen ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Respiratory Disease ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
The Novel ◽  
Targeted Therapeutics ◽  
Human Coronavirus ◽  
Prevention And Treatment

AbstractThe emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV). This cross-neutralizing antibody targets a communal epitope on these viruses and offers potential for prevention and treatment of COVID-19.

scholarly journals A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Aušra Domanska ◽  
Justin W. Flatt ◽  
Joonas J. J. Jukonen ◽  
James A. Geraets ◽  
Sarah J. Butcher
Keyword(s):  
Electron Microscopy ◽  
Monoclonal Antibody ◽  
High Resolution ◽  
Cultured Cells ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Human Parechovirus ◽  
Cryo Electron Microscopy

ABSTRACTHuman parechovirus 3 (HPeV3) infection is associated with sepsis characterized by significant immune activation and subsequent tissue damage in neonates. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and the lack of a vaccine or specific antiviral therapy. Toward the latter, we present a 2.8-Å-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody, AT12-015, using cryo-electron microscopy (cryo-EM) and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally, at high resolution, it was possible to model a stretch of RNA inside the virion and, from this, identify the key features that drive and stabilize protein-RNA association during assembly.IMPORTANCEHuman parechovirus 3 (HPeV3) is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, for which, despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Toward this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing monoclonal antibody. At high resolution, it was possible to precisely define the epitope that, when targeted, prevents virions from binding to cells. Such an atomic-level description is useful for understanding host-pathogen interactions and viral pathogenesis mechanisms and for finding potential cures for infection and disease.

scholarly journals Evaluation of Human Monoclonal Antibody 80R for Immunoprophylaxis of Severe Acute Respiratory Syndrome by an Animal Study, Epitope Mapping, and Analysis of Spike Variants

2005 ◽  
Vol 79 (10) ◽  
pp. 5900-5906 ◽  
Author(s):  
Jianhua Sui ◽  
Wenhui Li ◽  
Anjeanette Roberts ◽  
Leslie J. Matthews ◽  
Akikazu Murakami ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Amino Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
Index Patient ◽  
Binding Domain ◽  
S Protein

ABSTRACT 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 reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.

scholarly journals COVID-19 pandemic: The deadly respiratory disease of 21st century

2021 ◽  
Vol 11 (1) ◽  
pp. 01-18
Author(s):  
Shweta Jain ◽  
◽  
Pankaj Kumar Jain ◽  
Ramakant Yadav ◽  
Surendra Kumar Jain ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Disease ◽  
Clinical Investigation ◽  
Respiratory Illness ◽  
The Novel ◽  
Major Threat ◽  
The World ◽  
Prevention And Treatment ◽  
Novel Coronavirus ◽  
Severe Respiratory Illness

The sudden outbreak of 2019 novel coronavirus (2019-nCoV) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated from Wuhan, China. SARS-CoV-2 causes severe respiratory illness and becomes a major threat for humanity. Recently the entire scientist, researchers and physicians all over the countries focused to find the treatment of this pandemic disease. Numerous drugs and or vaccines have been trialed for prevention and treatment against 2019-nCoV but no therapy has been shown effective to date. Currently, numerous vaccines are under clinical investigation and mRNA-1273 vaccine (LNP- encapsulated mRNA vaccine encoding S protein) from Moderna is ahead. Although chloroquine, hydroxychloroquine, remdesivir and many other drugs had recommended against SARS-CoV-2, but still they are not the guarantee treatment of COVID-19. Recently, India, America, Russia and China introduced vaccines against COVID-19 in the market, however assurance of their 100% effectiveness are doubtful. The speed of daily new cases threatens the world and urges the scientist to crack this pandemic condition. KEYWORDS: 2019-nCoV; Chloroquine; COVID-19; Moderna; Respiratory disease; Remdesivir.

scholarly journals 2.8 Å resolution cryo-EM structure of human parechovirus 3 in complex with Fab from a neutralizing antibody

2018 ◽  
Author(s):  
Aušra Domanska ◽  
Justin W. Flatt ◽  
Joonas J.J. Jukonen ◽  
James A. Geraets ◽  
Sarah J. Butcher
Keyword(s):  
Monoclonal Antibody ◽  
High Resolution ◽  
Cultured Cells ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Human Parechovirus ◽  
Neutralizing Monoclonal Antibody ◽  
Specific Antiviral Therapy

AbstractHuman parechovirus 3 (HPeV3) infection is associated with sepsis in neonates characterized by significant immune activation and subsequent tissue damage. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and lack of a vaccine or specific antiviral therapy. Towards the latter, we present a 2.8 Å-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody AT12-015 using cryo-EM and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally at high-resolution, it was possible to model a stretch of RNA inside the virion and from this identify the key features that drive and stabilize protein-RNA association during assembly.ImportanceHPeV3 is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, which despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Towards this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing monoclonal antibody. At high-resolution it was possible to precisely define the epitope that when targeted, prevents virions from binding to cells. Such an atomic-level description is useful for understanding host-pathogen interaction, viral pathogenesis mechanisms, and for finding potential cures for infection and disease.

scholarly journals Study of the interactions of a novel monoclonal antibody, mAb059c, with the hPD-1 receptor

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jingxian Liu ◽  
Guiqun Wang ◽  
Liu Liu ◽  
Runjie Wu ◽  
Yi Wu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Salt Bridge ◽  
Regulatory Agencies ◽  
The Novel ◽  
Medical Needs ◽  
Cell Functions ◽  
Glycosylation Sites ◽  
Programmed Cell Death 1 ◽  
Fragment Antigen Binding

AbstractProgrammed cell death 1 (PD-1) monoclonal antibodies have been approved by regulatory agencies for the treatment of various types of cancer, and the mechanism involves the restoration of T cell functions. We report herein the X-ray crystal structure of a fully human monoclonal antibody mAb059c fragment antigen-binding (Fab) in complex with the PD-1 extracellular domain (ECD) at a resolution of 1.70 Å. Structural analysis indicates 1) an epitope, comprising fragments from the C’D, BC and FG loops of PD-1, contributes to mAb059c interaction, 2) an unique conformation of the C’D loop and a different orientation of R86 enabling the capture of PD-1 by the antibody complementarity determining region (CDR) and the formation of one salt-bridge contact – ASP101(HCDR3):ARG86(PD-1), and 3) the contact of FG with light chain (LC) CDR3 is maintained by a second salt-bridge and two backbone hydrogen bonds. Interface analysis reveals that N-glycosylation sites 49, 74 and 116 on PD-1 do not contact mAb059c; while N58 in the BC loop is recognized by mAb059c heavy chain CDR1 and CDR2. Mutation of N58 attenuated mAb059c binding to PD-1. These findings and the novel anti-PD-1 antibody will facilitate better understanding of the mechanisms of the molecular recognition of PD-1 receptor by anti-PD-1 mAb and, thereby, enable the development of new therapeutics with an expanded spectrum of efficacy for unmet medical needs.

scholarly journals Cell and animal models of SARS-CoV-2 pathogenesis and immunity

2020 ◽  
Vol 13 (9) ◽  
pp. dmm046581 ◽  
Author(s):  
Sarah R. Leist ◽  
Alexandra Schäfer ◽  
David R. Martinez
Keyword(s):  
Monoclonal Antibody ◽  
Animal Models ◽  
Global Health ◽  
Respiratory Disease ◽  
Protective Immunity ◽  
Viral Pathogenesis ◽  
The Novel ◽  
Cell Models ◽  
Sars Coronavirus ◽  
Novel Virus

ABSTRACTThe spread of the novel virus SARS coronavirus 2 (SARS-CoV-2) was explosive, with cases first identified in December 2019, and >22 million people infected and >775,000 deaths as of August 2020. SARS-CoV-2 can cause severe respiratory disease in humans leading to coronavirus disease 2019 (COVID-19). The development of effective clinical interventions, such as antivirals and vaccines that can limit or even prevent the burden and spread of SARS-CoV-2, is a global health priority. Testing of leading antivirals, monoclonal antibody therapies and vaccines against SARS-CoV-2 will require robust animal and cell models of viral pathogenesis. In this Special Article, we discuss the cell-based and animal models of SARS-CoV-2 infection and pathogenesis that have been described as of August 2020. We also outline the outstanding questions for which researchers can leverage animal and cell-based models to improve our understanding of SARS-CoV-2 pathogenesis and protective immunity. Taken together, the refinement of models of SARS-CoV-2 infection will be critical to guide the development of therapeutics and vaccines against SARS-CoV-2 to end the COVID-19 pandemic.

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