Therapeutics Development for COVID-19 and Viral Diseases

Research Tools and Resources

Therapeutic Development for Viral Diseases

There is an urgent need to develop therapeutic approaches to limit the spread and impact of the SARS-CoV-2 virus. Efforts are directed both toward qualifying existing drugs as safe and efficacious to use in the context of COVID-19 and developing novel therapeutic agents that specifically target SARS-CoV-2.

Pharmaceutical companies have ramped up their work to identify and generate monoclonal antibodies (mAbs) that can be used to neutralize SARS-CoV-2. Cellular therapy, successful in the treatment of diseases such as cancer, may also have applications in the treatment of COVID-19 or its long-lasting effects. Regardless of the class of therapy being developed, researchers are reliant upon in vitro models to provide predictive insight into the magnitude and mechanism of both therapeutic effect and possible toxicity.

Explore technologies, applications, and research tools for developing therapeutics to combat viral diseases.



Therapeutic Antibody Generation

Therapeutic Antibody Generation

Monoclonal antibodies (mAbs) that target specific protein epitopes are promising therapies for a variety of diseases, including viral infection. Antibody therapeutics specific to viral proteins can neutralize the virus by binding to it and preventing it from entering host cells and replicating.

The efficacy of therapeutic antibodies for COVID-19 specifically is supported by results of the use of convalescent plasma in critical patients.1, 2 Multiple strategies, including generating hybridomas and immortalizing primary human B cells, can be used to develop mAb antiviral therapies against SARS-CoV-2.

Using Hybridomas for Monoclonal Antibody Generation

Hybridomas are often generated from the fusion of myeloma cells and the B cells of wild-type or humanized mice as an early step in therapeutic monoclonal antibody development. This step allows for isolation of single antibody sequences that recognize and bind to the target antigen with high affinity.

The efficiency of hybridoma generation can be enhanced by: increasing the number of productive fusions between splenocytes and myeloma cells; decreasing the resources needed to generate a library of unique clones; increasing the diversity of clones isolated; and increasing the survival and expansion capacity of hybridoma clones under stressful conditions. Prior to fusion, isolating B cells with EasySep™ Mouse CD138 Positive Selection Kit can dramatically increase the efficiency of hybridoma fusion, while ClonaCell™-HY media provide robust growth conditions for fusion, cloning, and hybridoma expansion (Figure 1).

Figure 1. Hybridoma Workflow Using ClonaCell™ and EasySep™

The dissociated spleen (or other lymphoid tissue) from an immunized animal is used in fusion reactions with myeloma cells to generate hybridomas. EasySep™ Mouse CD138 Kit enriches for antibody-secreting cells prior to fusion. Hybridomas are selected for antibody secretion and target specificity, and the desired clones are stabilized over time using ClonaCell™-HY Medium E or ClonaCell™-HY AOF Expansion Medium.

Products for Hybridoma Generation


Hybridoma Generation, Cloning, and Expansion
Catalog #
ClonaCell™-HY Hybridoma Kit
ClonaCell™-HY Medium E
ClonaCell™-HY AOF Expansion Medium
ClonaCell™-HY Medium D
Isolation of Mouse B Cells Prior to Hybridoma Fusion
Catalog #
EasySep™ Mouse CD138 Positive Selection Kit
EasySep™ Mouse Pan-B Cell Isolation Kit
RoboSep™-16
  • For fully automated cell separations from up to 16 samples

Studies of SARS-CoV with ClonaCell™

Nieto-Torres JL et al. (2011) Subcellular location and topology of severe acute respiratory syndrome coronavirus envelope protein. Virology 415(2): 69–82.

Researchers generated mAbs to study the subcellular localization of a SARS-CoV protein during infection. They supported hybridoma clone survival and expansion with ClonaCell™-HY Medium E.


Lip KM et al. (2006) Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus. J Virol 80(2): 941–50.

Researchers used the ClonaCell™-HY Kit (for steps from pre-fusion culture to hybridoma expansion) to generate monoclonal hybridomas using the semi-solid cloning method. They studied the interactions between the mAbs made by these hybridomas and purified viral protein.


Berry JD et al. (2004) Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus. J Virol Methods 120(1): 87–96.

To generate mAbs that recognize the spike proteins of SARS-CoV, a research group in Canada used semi-solid cloning in ClonaCell™- HY Medium D to simultaneously select for successful hybridoma fusion and isolate individual hybridoma clones. Two of the spike-specific mAbs demonstrated the ability to neutralize SARS-CoV in vitro.

Antibody Generation with Primary Human B Cells

An efficient alternative to generating hybridomas is immortalizing primary human B cells.3 Although the speed and efficiency of this approach depends on the screening and transfection methods employed, using techniques like transient transfection can reduce the timeframe for assessing the initial viral neutralization potential of candidate recombinant mAbs to one week. Researchers have successfully employed this approach to obtain neutralizing antibodies against SARS-CoV from immortalized memory B cells obtained from recovered patients.4 Naïve B cell populations can also be used to generate potent virus-neutralizing human mAbs. These can be expanded using ImmunoCult™-ACF Human B Cell Expansion Supplement. You can further streamline mAb generation by using EasySep™, a smarter, more efficient way to isolate cells, and by choosing a trusted supplier for human primary cells.

Products for Antibody Generation with Primary Human B Cells


Ethically Sourced Human Blood Products*
Catalog #
Human Peripheral Blood Leukopak, Fresh*
Human Peripheral Blood Leukopak, Frozen*
LRS Cone*
Human Peripheral Blood Mononuclear Cells, Frozen
Human Peripheral Blood B Cells, Frozen
Human Peripheral Blood CD19+ B Cells, Frozen
Human Peripheral Blood CD19+CD27- Naïve B Cells, Frozen

*For information about COVID-19 and primary cells, please see our frequently asked questions (FAQ). Certain products are only available in select territories.



Isolation and Expansion of Human B Cells
Catalog #
EasySep™ Human Pan-B Cell Enrichment Kit
EasySep™ Human CD19 Positive Selection Kit II
EasySep™ Human Memory B Cell Isolation Kit
EasySep™ Human CD138 Positive Selection Kit II
EasySep™ Human Whole Blood & Bone Marrow CD138 Positive Selection Kit II
ImmunoCult™-ACF Human B Cell Expansion Supplement
RoboSep™-16
  • For fully automated cell separations from up to 16 samples

Antibody Production in CHO Cells

To manufacture antibody therapeutics, mAbs need to be produced as recombinant proteins in expression systems with a proven safety profile, such as Chinese hamster ovary (CHO) cells. To support cell survival and expansion during cloning and other vulnerable stages of cell line development, use ClonaCell™-CHO ACF Supplement, which is compatible with a wide variety of workflows and platforms.

Products for Antibody Production in CHO Cells


CHO Cell Line Cloning and Expansion
Catalog #
ClonaCell™-CHO ACF Supplement
ClonaCell™-CHO ACF Medium
ClonaCell™ FLEX

Immunoassays

In early development phases, mAb-producing cell lines are assessed to identify high-producing lines. Researchers often rely on highly sensitive enzyme-linked immunosorbent assays (ELISAs) to ensure accurate quantification of mAbs.

Products to Quantify mAbs


Product
Catalog #
Human IgG ELISA Antibody Pair Kit

Convalescent Plasma Therapy Research

In this classical adaptive immunotherapy, convalescent plasma from recovered patients is used to treat patients with viral infections. Lacking an established therapeutic approach for COVID-19, physicians are investigating convalescent plasma therapy as an option in critical cases, with promising initial results.1,2

To obtain the antibodies from a recovered patient, scientists need to isolate plasma from individual blood samples. Patient blood samples can be processed quickly and consistently by using SepMate™ and Lymphoprep™ for streamlined density gradient centrifugation, where samples can be rapidly added to tubes and the top layer easily pipetted off.

Products for Isolating Plasma


Plasma Isolation
Catalog #
SepMate™ PBMC Isolation Tubes
Lymphoprep™

Cellular Therapy Research

Immunotherapy, which strengthens the body's own immune system to fight disease, is another approach under investigation for the treatment of viral diseases.

NK Cell-Based Therapy Research

Natural killer (NK) cell-based therapies harness the ability of NK cells to target and lyse antibody-bound infected cells through an immune response process called antibody-dependent cellular cytotoxicity (ADCC). Recent research has shown that NK cells can exert antiviral activity via ADCC against SARS-CoV-2.5 You can use pre-isolated, ethically sourced human NK cells, or isolate them yourself from human blood products using EasySep™. Alternatively, CD56+ NK cells can be generated from cord blood-derived CD34+ cells or differentiated from human pluripotent stem cells (hPSCs).

Products for NK Cell-Based Therapy Research


Sourcing and Isolation of Primary Human NK Cells
Catalog #
Human Peripheral Blood Leukopak, Fresh*
Human Peripheral Blood Leukopak, Frozen*
LRS Cone*
Human Whole Peripheral Blood*
Human Peripheral Blood CD56+ NK Cells, Frozen*
Human Cord Blood CD56+ NK Cells, Frozen*
EasySep™ Human NK Cell Isolation Kit
RoboSep™-S
  • For fully automated cell separations
Expansion and Differentiation to NK Cells
Application
Catalog #
STEMdiff™ NK Cell Kit
Expansion and differentiation of hPSCs to NK cells
Human Cord Blood CD34+ Cells, Frozen*
Ethically sourced cells that can be expanded and differentiated in vitro
EasySep™ Human Cord Blood CD34 Positive Selection Kit II
Isolation of CD34+ cells from cord blood
StemSpan™ NK Cell Generation Kit
Expansion and differentiation of human CD34+ hematopoietic progenitor cells to NK cells
Characterization of NK Cells
Catalog #
Anti-Human CD56 (NCAM) Antibody, Clone HCD56
Anti-Human CD16 Antibody, Clone 3G8

*For information about COVID-19 and primary cells, please see our frequently asked questions (FAQ). Certain products are only available in select territories.

T Cell Therapy Research

T cell therapy is also under investigation as a treatment approach for viral diseases, including COVID-19.6 This form of immunotherapy uses specially altered T cells to target and kill infected cells. You can isolate T cells for cell therapy research from ethically sourced whole blood or leukapheresis products, or purchase pre-isolated cryopreserved Pan-T cells. T cells can then be expanded in vitro. Alternatively, T cells can be generated from cord blood-derived CD34+ cells or differentiated from hPSCs.

Products for T Cell Therapy Research


Sourcing and Isolation of Primary Human T Cells
Catalog #
Human Peripheral Blood Leukopak, Fresh*
Human Peripheral Blood Leukopak, Frozen*
LRS Cone*
Human Whole Peripheral Blood*
Human Peripheral Blood Pan-T Cells, Frozen*
Human Cord Blood Pan-T Cells, Frozen*
EasySep™ Human T Cell Isolation Kit
EasySep™ Human CD4+ T Cell Isolation Kit
EasySep™ Human CD8+ T Cell Isolation Kit
RoboSep™-S
  • For fully automated cell separations
Expansion and Activation of Human T Cells
Catalog #
ImmunoCult™-XF T Cell Expansion Medium
Human Recombinant IL-2 (CHO-expressed)
ImmunoCult™ Human CD3/CD28 T Cell Activator
ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator
Expansion and Differentiation to T Cells
Application
Catalog #
STEMdiff™ T Cell Kit
Expansion and differentiation of hPSCs to T cells
Human Cord Blood CD34+ Cells, Frozen*
Ethically sourced cells that can be expanded and differentiated in vitro
EasySep™ Human Cord Blood CD34 Positive Selection Kit II
Isolation of CD34+ cells from cord blood
StemSpan™ T Cell Generation Kit
Expansion and differentiation of human CD34+ hematopoietic progenitor cells to T cells
Characterization and Gene Editing of T Cells
Catalog #
Anti-Human CD4 Antibody, Clone OKT4
Anti-Human CD8a Antibody, Clone RPA-T8
Anti-Human CD3 Antibody, Clone UCHT1
ArciTect™ CRISPR-Cas9 Genome Editing System

*For information about COVID-19 and primary cells, please see our frequently asked questions (FAQ). Certain products are only available in select territories.

Hematopoietic Cell Therapeutic Development for SARS-CoV-2

There is growing interest in studying the effects of expanded cord blood-derived CD34+ cells in patients with COVID-19. These cells may have an effect on inflammation associated with infection. You can isolate CD34+ cells using EasySep™, culture and expand them in StemSpan™-ACF Without Phenol Red, and finally test their potency by performing CFU assays in MethoCult™ H4034 Optimum.

Products for Hematopoietic Cell Therapy Research


Sourcing and Isolation of Primary Human CD34+ Cells
Catalog #
Human Cord Blood CD34+ Cells, Frozen*
EasySep™ Human Cord Blood CD34 Positive Selection Kit II
EasySep™ Human Blood CD34 Positive Selection Kit II
RoboSep™-S
  • For fully automated cell separations

*For information about COVID-19 and primary cells, please see our frequently asked questions (FAQ). Certain products are only available in select territories.

Culture and Expansion of Human Hematopoietic Cells
Catalog #
StemSpan™ SFEM II
StemSpan™-XF
StemSpan™-ACF Without Phenol Red
StemSpan™ CD34+ Expansion Supplement (10X)
UM729
Potency Testing
Catalog #
MethoCult™ H4034 Optimum
SmartDish™
STEMvision™

In Vitro Assays and Models

In Vitro Assays and Models

Researchers have the opportunity to optimize development pipelines by using relevant human model systems to assess critical characteristics such as efficacy, mechanism of action, and toxicity of therapeutics in vitro. Incorporating these experiments at strategic points during development can help save valuable time by informing decisions on the best candidates to move forward.

In Vitro Human Tissue Modeling

Using physiologically relevant human model systems, researchers can gain critical, predictive results for drug screening and toxicity testing. Human in vitro models—including cultures generated by directed differentiation of hPSCs—that recapitulate characteristics at the cellular and tissue levels are being increasingly adopted at various stages during therapeutic development.

Air-liquid interface (ALI) cultures of human airway epithelial cells form pseudostratified mucociliary epithelial layers that closely model the in vivo airway, making these cultures a uniquely suited model system for studying respiratory infections in vitro. Similarly, human organoids modeling various human tissues provide in vitro model systems that incorporate multiple tissue-specific cell types and model tissue-specific cellular organization. Explore how in vitro intestinal and kidney model systems can be used to study COVID-19.

Products for In Vitro Human Tissue Modeling


Stabilized, Feeder-Free Maintenance of hPSCs
Catalog #
mTeSR™ Plus

Modeling the Human Nervous System
Application
Catalog #
BrainPhys™ Neuronal Medium
Culturing primary neurons or neurons derived from human pluripotent stem cells (hPSCs)
STEMdiff™ Forebrain Neuron Differentiation Kit
Generating forebrain-type neurons from hPSC-derived neural progenitor cells
STEMdiff™ Cerebral Organoid Kit
Generating hPSC-derived cerebral organoids

Modeling Epithelial Tissues
Application
Catalog #
PneumaCult™-ALI Medium
Generating ALI cultures from primary airway cells
PneumaCult™ Airway Organoid Kit
Generating airway organoids from human bronchial epithelial cells
STEMdiff™ Branching Lung Organoid Kit
Generating hPSC-derived branching lung organoids
STEMdiff™ Lung Progenitor Kit
Generating hPSC-derived lung progenitor cells
STEMdiff™ Kidney Organoid Kit
Generating hPSC-derived kidney organoids
IntestiCult™ Organoid Growth Medium (Human)
Generating intestinal organoids from primary human intestinal stem cells
STEMdiff™ Intestinal Organoid Kit
Generating hPSC-derived intestinal organoids

Learn more about airway ALI, kidney organoid, and intestinal organoid models for COVID-19 research.

See all organoid products >


Modeling Cardiac and Endothelial Tissue
Application
Catalog #
STEMdiff™ Cardiomyocyte Differentiation Kit
Generating hPSC-derived cardiomyocytes
STEMdiff™ Endothelial Differentiation Kit
Generating hPSC-derived endothelial-like cells

Recombinant Spike, Nucleocapsid, and Human ACE2 Protein

Product
Catalog #
SARS-CoV-2 Recombinant Nucleocapsid Protein, aa1-419 (E. coli-expressed)
SARS-CoV-2 Recombinant Nucleocapsid Protein, aa1-419 (HEK293-expressed)
SARS-CoV-2 Recombinant Spike Protein, aa16-685 (HEK293-expressed)
SARS-CoV-2 Recombinant Spike Protein, aa319-541 (Yeast-expressed)
Human Recombinant ACE2 Protein, aa18-740 (HEK293-expressed)

Products for Targeting SARS-CoV-2 Nucleoprotein and Spike Protein

Product
Catalog #
Anti-SARS-CoV Nucleoprotein Antibody, Clone 001 (Recombinant)
Anti-SARS-CoV Spike Protein S1 Receptor-Binding Domain Antibody, Clone D005 (Recombinant)
Anti-SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain Antibody, Clone Covi-1 (Blocking/Recombinant)
Anti-SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain Antibody, Clone Covi-2 (Blocking/Recombinant)

Products for Detection of CoV Proteases

Product Catalog #
CoV Protease Substrate-1 TF5 100-0505
CoV Protease Substrate-1 EDANS 100-0507
CoV Protease Substrate-2 EDANS 100-0509
CoV Protease Substrate-2 IF670 100-0511

Hematotoxicity Testing

Toxicity affecting blood cells can lead to serious conditions, such as anemia, neutropenia, or thrombocytopenia. Toxic effects on hematopoietic stem and progenitor cells may cause cell death, or more subtle changes in the ability of these cells to properly proliferate and differentiate to the downstream lineages that make up circulating blood.

To test for potential hematotoxicity, primary human CD34+ cells can be expanded and differentiated in vitro to specific downstream lineages using HemaTox™ Kits. Test compounds are added during the culture periods to assess their effects on the generation of specific downstream cell lineages. IC50 values for test compounds can then be determined by flow cytometry analysis.

Find efficiencies in your hematotoxicity assays by using EasySep™ to isolate hematopoietic stem and progenitor cells, and by choosing a reliable supplier for human primary cells.

Products for Hematotoxicity Testing


Sourcing and Isolation of Primary Human CD34+ Cells
Catalog #
Human Cord Blood CD34+ Cells, Frozen*
EasySep™ Human Cord Blood CD34 Positive Selection Kit II
EasySep™ Human Blood CD34 Positive Selection Kit II
RoboSep™-S
  • For fully automated cell separations

*For information about COVID-19 and primary cells, please see our frequently asked questions (FAQ). Certain products are only available in select territories.

Measurement of Hematotoxicity
Catalog #
HemaTox™ Erythroid Kit
HemaTox™ Myeloid Kit
HemaTox™ Megakaryocyte Kit

Contract Assay Services

Therapeutic Development for Viral Diseases

Engaging the right expertise and resources can be an effective way to create efficiencies in your drug development pipeline. Our Contract Assay Services team combines optimized media, pre-qualified cells, and specialized expertise to screen candidate therapeutics in primary cell-based assays.

If you are interested in Contract Assay Services, including toxicity testing and pulmonary services, contact us to find out how we can help you meet your goals.



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