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1.
Nat Commun ; 13(1): 4054, 2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1931408

ABSTRACT

Establishment of zoonotic viruses, causing pandemics like the Spanish flu and Covid-19, requires adaptation to human receptors. Pandemic influenza A viruses (IAV) that crossed the avian-human species barrier switched from binding avian-type α2-3-linked sialic acid (2-3Sia) to human-type 2-6Sia receptors. Here, we show that this specificity switch is however less dichotomous as generally assumed. Binding and entry specificity were compared using mixed synthetic glycan gradients of 2-3Sia and 2-6Sia and by employing a genetically remodeled Sia repertoire on the surface of a Sia-free cell line and on a sialoglycoprotein secreted from these cells. Expression of a range of (mixed) 2-3Sia and 2-6Sia densities shows that non-binding human-type receptors efficiently enhanced avian IAV binding and entry provided the presence of a low density of high affinity avian-type receptors, and vice versa. Considering the heterogeneity of sialoglycan receptors encountered in vivo, hetero-multivalent binding is physiologically relevant and will impact evolutionary pathways leading to host adaptation.


Subject(s)
COVID-19 , Influenza A virus , Influenza Pandemic, 1918-1919 , Influenza, Human , Animals , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Humans , Influenza A virus/metabolism , N-Acetylneuraminic Acid/metabolism , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Receptors, Virus/metabolism
2.
Vaccine ; 2022 Jul 06.
Article in English | MEDLINE | ID: covidwho-1915072

ABSTRACT

The emergence of SARS-CoV-2 in December 2019 resulted in the COVID-19 pandemic. Recurring disease outbreaks repeatedly overloaded the public health sector and severely affected the global economy. We developed a candidate COVID-19 vaccine based on a recombinant Newcastle disease virus (NDV) vaccine vector, encoding a pre-fusion stabilized full-length Spike protein obtained from the original SARS-CoV-2 Wuhan isolate. Vaccination of hamsters by intra-muscular injection or intra-nasal instillation induced high neutralizing antibody responses. Intranasal challenge infection with SARS-CoV-2 strain Lelystad demonstrated that both vaccination routes provided partial protection in the upper respiratory tract, and almost complete protection in the lower respiratory tract, as measured by suppressed viral loads and absence of histological lung lesions. Activity wheel measurements demonstrated that animals vaccinated by intranasal inoculation rapidly recovered to normal activity. NDV constructs encoding the spike of SARS-CoV-2 may be attractive candidates for development of intra-nasal COVID-19 booster vaccines.

3.
Nat Commun ; 13(1): 2921, 2022 05 25.
Article in English | MEDLINE | ID: covidwho-1864741

ABSTRACT

Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1A domain, but, remarkably, also to S1B. The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1B epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2.


Subject(s)
COVID-19 , Coronavirus OC43, Human , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus OC43, Human/metabolism , Epitopes , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
4.
Sci Immunol ; 7(73): eabp9312, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1807305

ABSTRACT

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other variants of concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.


Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Animals , Antibodies, Neutralizing/pharmacology , COVID-19/drug therapy , Cryoelectron Microscopy , Humans , Membrane Glycoproteins , Mice , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins
5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327732

ABSTRACT

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity. One sentence summary A human monoclonal antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

6.
ChemMedChem ; 16(23):3495-3495, 2021.
Article in English | Wiley | ID: covidwho-1557779

ABSTRACT

The Front Cover shows bithiazole derivatives acting as broad-spectrum antiviral agents (BSAAs) by targeting human host cells. These molecules block the replication of human rhinoviruses (hRVs) and Zika virus (ZIKV) via inhibition of the intracellular protein PI4KIII? while the inhibition of SARS-CoV-2 entry and replication seems to be connected with the modulation of an additional target. Cover design by Marco Radi. More information can be found in the Communication by Maria?Grazia Martina, Marco Radi et?al.

7.
NPJ Vaccines ; 6(1): 122, 2021 Oct 20.
Article in English | MEDLINE | ID: covidwho-1475297

ABSTRACT

Early in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.

8.
ChemMedChem ; 16(23): 3548-3552, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1400781

ABSTRACT

Over half a century since the description of the first antiviral drug, "old" re-emerging viruses and "new" emerging viruses still represent a serious threat to global health. Their high mutation rate and rapid selection of resistance toward common antiviral drugs, together with the increasing number of co-infections, make the war against viruses quite challenging. Herein we report a host-targeted approach, based on the inhibition of the lipid kinase PI4KIIIß, as a promising strategy for inhibiting the replication of multiple viruses hijacking this protein. We show that bithiazole inhibitors of PI4KIIIß block the replication of human rhinoviruses (hRV), Zika virus (ZIKV) and SARS-CoV-2 at low micromolar and sub-micromolar concentrations. However, while the anti-hRV/ZIKV activity can be directly linked to PI4KIIIß inhibition, the role of PI4KIIIß in SARS-CoV-2 entry/replication is debated.


Subject(s)
1-Phosphatidylinositol 4-Kinase/antagonists & inhibitors , Antiviral Agents/pharmacology , Enzyme Inhibitors/chemistry , Rhinovirus/physiology , SARS-CoV-2/physiology , Thiazoles/chemistry , Virus Replication/drug effects , Zika Virus/physiology , 1-Phosphatidylinositol 4-Kinase/metabolism , Antiviral Agents/chemistry , Antiviral Agents/metabolism , COVID-19/pathology , COVID-19/virology , Cell Line , Drug Stability , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Humans , SARS-CoV-2/isolation & purification , Thiazoles/metabolism , Zika Virus/isolation & purification , Zika Virus Infection/pathology
9.
Nat Commun ; 11(1): 2511, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-1387317

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

10.
Nat Commun ; 12(1): 4586, 2021 07 28.
Article in English | MEDLINE | ID: covidwho-1387355

ABSTRACT

Heterogeneous immunoassays such as ELISA have become indispensable in modern bioanalysis, yet translation into point-of-care assays is hindered by their dependence on external calibration and multiple washing and incubation steps. Here, we introduce RAPPID (Ratiometric Plug-and-Play Immunodiagnostics), a mix-and-measure homogeneous immunoassay platform that combines highly specific antibody-based detection with a ratiometric bioluminescent readout. The concept entails analyte-induced complementation of split NanoLuc luciferase fragments, photoconjugated to an antibody sandwich pair via protein G adapters. Introduction of a calibrator luciferase provides a robust ratiometric signal that allows direct in-sample calibration and quantitative measurements in complex media such as blood plasma. We developed RAPPID sensors that allow low-picomolar detection of several protein biomarkers, anti-drug antibodies, therapeutic antibodies, and both SARS-CoV-2 spike protein and anti-SARS-CoV-2 antibodies. With its easy-to-implement standardized workflow, RAPPID provides an attractive, fast, and low-cost alternative to traditional immunoassays, in an academic setting, in clinical laboratories, and for point-of-care applications.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoassay/standards , Luminescent Measurements/standards , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Serological Testing/instrumentation , Calibration , GTP-Binding Proteins/chemistry , Genes, Reporter , Humans , Immunoconjugates/chemistry , Limit of Detection , Luciferases/genetics , Luciferases/metabolism , Point-of-Care Testing , SARS-CoV-2/genetics
11.
Commun Biol ; 4(1): 631, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1283664

ABSTRACT

IL22 is an important cytokine involved in the intestinal defense mechanisms against microbiome. By using ileum-derived organoids, we show that the expression of anti-microbial peptides (AMPs) and anti-viral peptides (AVPs) can be induced by IL22. In addition, we identified a bacterial and a viral route, both leading to IL22 production by T cells, but via different pathways. Bacterial products, such as LPS, induce enterocyte-secreted SAA1, which triggers the secretion of IL6 in fibroblasts, and subsequently IL22 in T cells. This IL22 induction can then be enhanced by macrophage-derived TNFα in two ways: by enhancing the responsiveness of T cells to IL6 and by increasing the expression of IL6 by fibroblasts. Viral infections of intestinal cells induce IFNß1 and subsequently IL7. IFNß1 can induce the expression of IL6 in fibroblasts and the combined activity of IL6 and IL7 can then induce IL22 expression in T cells. We also show that IL22 reduces the expression of viral entry receptors (e.g. ACE2, TMPRSS2, DPP4, CD46 and TNFRSF14), increases the expression of anti-viral proteins (e.g. RSAD2, AOS, ISG20 and Mx1) and, consequently, reduces the viral infection of neighboring cells. Overall, our data indicates that IL22 contributes to the innate responses against both bacteria and viruses.


Subject(s)
Interleukins/biosynthesis , Interleukins/metabolism , Animals , Anti-Bacterial Agents/metabolism , Antiviral Agents/metabolism , Cell Culture Techniques , Cytokines/immunology , Cytokines/metabolism , Disease Models, Animal , Enterocytes/immunology , Enterocytes/metabolism , Female , Fibroblasts/immunology , Fibroblasts/metabolism , Interleukins/immunology , Intestinal Mucosa/metabolism , Intestines/physiology , Mice , Mice, Inbred C57BL , Myeloid Cells/immunology , Myeloid Cells/metabolism , Organoids/metabolism , Pore Forming Cytotoxic Proteins/genetics , Pore Forming Cytotoxic Proteins/metabolism
12.
Sci Adv ; 7(23)2021 06.
Article in English | MEDLINE | ID: covidwho-1219234

ABSTRACT

The emergence of SARS-CoV-2 antibody escape mutations highlights the urgent need for broadly neutralizing therapeutics. We previously identified a human monoclonal antibody, 47D11, capable of cross-neutralizing SARS-CoV-2 and SARS-CoV and protecting against the associated respiratory disease in an animal model. Here, we report cryo-EM structures of both trimeric spike ectodomains in complex with the 47D11 Fab. 47D11 binds to the closed receptor-binding domain, distal to the ACE2 binding site. The CDRL3 stabilizes the N343 glycan in an upright conformation, exposing a mutationally constrained hydrophobic pocket, into which the CDRH3 loop inserts two aromatic residues. 47D11 stabilizes a partially open conformation of the SARS-CoV-2 spike, suggesting that it could be used effectively in combination with other antibodies targeting the exposed receptor-binding motif. Together, these results reveal a cross-protective epitope on the SARS-CoV-2 spike and provide a structural roadmap for the development of 47D11 as a prophylactic or postexposure therapy for COVID-19.


Subject(s)
Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , SARS Virus , SARS-CoV-2 , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/immunology , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , Humans , SARS Virus/chemistry , SARS Virus/immunology , SARS-CoV-2/chemistry , SARS-CoV-2/immunology , Structure-Activity Relationship
13.
Emerg Infect Dis ; 27(5): 1362-1370, 2021 05.
Article in English | MEDLINE | ID: covidwho-1202205

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect many animal species, including minks, cats, and dogs. To gain insights into SARS-CoV-2 infections in cats and dogs, we developed and validated a set of serologic assays, including ELISA and virus neutralization. Evaluation of samples from animals before they acquired coronavirus disease and samples from cats roaming SARS-CoV-2-positive mink farms confirmed the suitability of these assays for specific antibody detection. Furthermore, our findings exclude SARS-CoV-2 nucleocapsid protein as an antigen for serologic screening of cat and dog samples. We analyzed 500 serum samples from domestic cats and dogs in the Netherlands during April-May 2020. We showed 0.4% of cats and 0.2% of dogs were seropositive. Although seroprevalence in cats and dogs that had unknown SARS-CoV-2 exposure was low during the first coronavirus disease wave, our data stress the need for development of continuous serosurveillance for SARS-CoV-2 in these 2 animal species.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cats , Dogs , Humans , Mink , Netherlands/epidemiology , Seroepidemiologic Studies
14.
Trends Microbiol ; 29(11): 983-992, 2021 11.
Article in English | MEDLINE | ID: covidwho-1187873

ABSTRACT

Efficient penetration of the mucus layer is needed for respiratory viruses to avoid mucociliary clearance prior to infection. Many respiratory viruses bind to glycans on the heavily glycosylated mucins that give mucus its gel-like characteristics. Influenza viruses, some paramyxoviruses, and coronaviruses avoid becoming trapped in the mucus by releasing themselves by means of their envelope-embedded enzymes that destroy glycan receptors. For efficient infection, receptor binding and destruction need to be in balance with the host receptor repertoire. Establishment in a novel host species requires resetting of the balance to adapt to the different glycan repertoire encountered. Growing understanding of species-specific mucosal glycosylation patterns and the dynamic interaction with respiratory viruses identifies the mucus layer as a major host-range determinant and barrier for zoonotic transfer.


Subject(s)
Host Specificity , Viruses , Glycosylation , Mucins/metabolism , Mucus/metabolism , Polysaccharides/metabolism , Viruses/metabolism
15.
Nat Commun ; 12(1): 1715, 2021 03 17.
Article in English | MEDLINE | ID: covidwho-1139739

ABSTRACT

The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.


Subject(s)
Antibodies, Monoclonal, Humanized/immunology , Betacoronavirus/immunology , Epitopes/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Betacoronavirus/classification , Camelus , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cross Reactions , Epitopes/chemistry , Epitopes/genetics , Humans , Mice , Protein Conformation , Protein Subunits , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
16.
Cell ; 183(7): 1930-1945.e23, 2020 12 23.
Article in English | MEDLINE | ID: covidwho-921845

ABSTRACT

RNA viruses are among the most prevalent pathogens and are a major burden on society. Although RNA viruses have been studied extensively, little is known about the processes that occur during the first several hours of infection because of a lack of sensitive assays. Here we develop a single-molecule imaging assay, virus infection real-time imaging (VIRIM), to study translation and replication of individual RNA viruses in live cells. VIRIM uncovered a striking heterogeneity in replication dynamics between cells and revealed extensive coordination between translation and replication of single viral RNAs. Furthermore, using VIRIM, we identify the replication step of the incoming viral RNA as a major bottleneck of successful infection and identify host genes that are responsible for inhibition of early virus replication. Single-molecule imaging of virus infection is a powerful tool to study virus replication and virus-host interactions that may be broadly applicable to RNA viruses.


Subject(s)
Protein Biosynthesis , RNA Viruses/physiology , Virus Replication/physiology , Cell Line, Tumor , Cell Survival , HEK293 Cells , Host-Pathogen Interactions , Humans , Interferons/metabolism , RNA Transport , RNA, Viral/genetics , Reproducibility of Results , Single Molecule Imaging , Time Factors
17.
Proc Natl Acad Sci U S A ; 117(41): 25759-25770, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-807358

ABSTRACT

Human coronaviruses OC43 and HKU1 are respiratory pathogens of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spillover. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S with hemagglutinin-esterase (HE) acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity toward clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations led to cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and coevolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein species, is unique among CoVs, but reminiscent of that of influenza A viruses. Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens.


Subject(s)
Coronavirus/physiology , Hemagglutinins, Viral/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Fusion Proteins/genetics , Virion/metabolism , Animals , Biological Evolution , Cell Line , Coronavirus/genetics , Coronavirus/metabolism , Coronavirus Infections/virology , Coronavirus OC43, Human/genetics , Coronavirus OC43, Human/metabolism , Coronavirus OC43, Human/physiology , Coronavirus, Bovine/genetics , Coronavirus, Bovine/metabolism , Coronavirus, Bovine/physiology , Hemagglutinins, Viral/chemistry , Hemagglutinins, Viral/metabolism , Humans , Lectins/genetics , Lectins/metabolism , Mice , Mutation , Protein Binding , Protein Domains , Receptors, Virus/metabolism , Selection, Genetic , Sialic Acids/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Viral Fusion Proteins/chemistry , Viral Fusion Proteins/metabolism , Virion/genetics , Virus Attachment , Virus Release
18.
Nat Commun ; 11(1): 2251, 2020 05 04.
Article in English | MEDLINE | ID: covidwho-164588

ABSTRACT

The 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) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/pharmacology , Antibody Affinity/immunology , Betacoronavirus/chemistry , Betacoronavirus/drug effects , COVID-19 , Chlorocebus aethiops , Conserved Sequence , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cross Reactions/immunology , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Humans , In Vitro Techniques , Inhibitory Concentration 50 , Models, Molecular , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Protein Binding/drug effects , Protein Domains/immunology , Receptors, Virus/chemistry , Receptors, Virus/metabolism , SARS Virus/chemistry , SARS Virus/drug effects , SARS Virus/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
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