Development of neutralizing nanobodies against SARS-CoV-2

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

↗ Live URL (may be dead)

Document text

Principal Investigator: Mitchell  Ho
Organization: DIVISION OF BASIC SCIENCES - NCI
Fiscal Year: 2021
Award: $22,016
Funding agency: National Cancer Institute

During the pandemic, Dr Ho has evaluated the challenges for developing antibody therapeutics targeting SARS-Cov-2 and wrote a review/perspective article [Ho Antibody Therapeutics 2020; PMID: 32566896]. SARS-CoV-2 gains entry to human cells through its spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2). Therefore, the S protein is the primary target for neutralizing antibodies. A cocktail strategy combining two (or more) antibodies that recognize different parts of the viral surface that interact with human cells might be the most effective. In FY2021, the Ho lab using phage display technology has identified a panel of camel nanobodies that might recognize diverse conformations of the RBD. Some might bind an "open" conformation of the RBD, which might block the interaction with the ACE2 on human cell, while others might bind a "close" conformation, which might lock its conformation in the off state. Epitope mapping of these nanobodies on the viral spike protein reveals two distinct binding epitopes, one is directly involved in the ACE2 binding and the other is conserved between SARS-CoV-2 and SARS-CoV. The top candidates that recognize these two distinct epitopes shows potent neutralization activities against SARS-CoV-2 variants B.1.1.7 and B.1.351. The 2-in-1 cocktail treatment with these two groups of nanobodies shows potent protection against the B.1.351 variant in mice, suggesting promising therapeutic potential to prevent and treat COVID-19. Ongoing studies will establish our nanobodies as a new family of anti-viral drugs for treating COVID-19 and potentially future coronavirus infections in humans. We are actively searching for industry partners to clinically develop our novel nanobodies targeting SARS-CoV-2 for treating COVID-19 pandemic.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><ACE2><Antibodies><Antigenic Determinants><Antiviral Agents><Antiviral Drugs><Antivirals><B.1.1.7><B.1.351><Bacteriophages><Binding><Binding Determinants><Binding Proteins><Biological><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 S protein><COVID-19 antibody><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 prevention><COVID-19 public health crisis><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 therapy><COVID-19 treatment><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID19><COVID19 S protein><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 prevention><COVID19 public health crisis><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 therapy><COVID19 treatment><COVID19 virus><CV-19><CV19><Camels><Cell Body><Cells><Clinical><CoV-2><CoV2><Coronaviridae Infections><Coronavirus Infections><Development><Epitope Mapping><Epitopes><Family><Future><Human><Libraries><Ligand Binding Protein><Ligand Binding Protein Gene><Mice><Mice Mammals><Modern Man><Molecular Configuration><Molecular Conformation><Molecular Interaction><Molecular Stereochemistry><Murine><Mus><Phage Display><Phages><Protein Binding><Proteins><Research><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><SARS-CoV-2 B.1.1.7><SARS-CoV-2 B.1.351><SARS-CoV-2 S protein><SARS-CoV-2 antibody><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 therapy><SARS-CoV-2 treatment><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 antibody><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Shark><South Africa variant><South African variant><Structure><Surface><Technology><Therapeutic><Therapeutic antibodies><U.K. variant><UK variant><United Kingdom variant><Variant><Variation><Viral><Wuhan coronavirus><angiotensin converting enzyme 2><angiotensin converting enzyme II><anti-viral agents><anti-viral drugs><anti-virals><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><bacterial virus><bound protein><conformation><conformational state><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 antibody><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 prevention><coronavirus disease 2019 public health crisis><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 therapy><coronavirus disease 2019 treatment><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><developmental><global health><hCoV19><industrial partnership><industry partner><industry partnership><nCoV2><nanobodies><nanobody><neutralizing antibody><novel><pandemic><pandemic disease><prevent COVID-19><prevent COVID19><prevent coronavirus disease 2019><sdAb><severe acute respiratory syndrome coronavirus 2 B.1.1.7><severe acute respiratory syndrome coronavirus 2 B.1.351><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 therapy><severe acute respiratory syndrome coronavirus 2 treatment><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><severe acute respiratory syndrome-CoV><single domain antibodies><therapeutic target><treat COVID-19><treat COVID19><treat SARS-CoV-2><treat coronavirus disease 2019><treat severe acute respiratory syndrome coronavirus 2>