BPS Bioscience has developed innovative proteins, cell lines, lentiviruses, and assay kits, to enable a wide range of preclinical activities for investigating potential antiviral drugs. These kits and services aim to rapidly advance drugs into the clinic by screening for compounds that prevent the SARS-CoV-2 virus from binding to target cells, infecting the target cells, and replicating after it enters the host cell. Additionally, the pseudovirus-based infection assay services allow for rapid screening of antibodies and entry inhibitors as well as evaluating compounds for neutralization potential against the highly pathogenic SARS-CoV-2. Custom cell line development and cell-based screening can assist in studying these interactions at the cellular level.

Biochemical Screening

BPS Bioscience offers biochemical assay kits which can be used directly in your laboratory, or BPS can screen your compounds for you using our biochemical screening services and then provide with you a detailed report. We utilize five key types of assays for screening services: chemiluminescent, colorimetric, colorimetric IgG detection, TR-FRET, and fluorogenic detection.

• Our team of experts along with our broad services portfolio makes it easy to

• Papain-like Protease (SARS-CoV-2) Assay Kit: Protease Activity

• Papain-like Protease (SARS-CoV-2) Assay Kit: Deubiquitinase Activity

• RdRp (SARS-CoV-2) TR-FRET Assay Kit

• TMPRSS2 Assay

• ACE2 : SARS-CoV-2 Spike assays

• 3CL Protease Assays (SARS-CoV or SARS-CoV-2)

• Cathepsin B Assay

• Cathepsin L Assay

• Furin Protease Assay

• SARS-CoV-2 IgG Detection Kit (Colorimetric Anti-Spike RBD IgG detection)

• SARS-CoV-2 IgG Detection Kit (Colorimetric Trimer Anti-Spike IgG detection)

• Screen for inhibitors using biochemical assays

• Detect IgG binding to the Spike Trimer or Spike RBD for qualitative detection of human IgG antibodies in serum collected from individuals suspected of prior infection with the virus that causes

• Cell based screening services are also available using Spike lentivirus / ACE2 cell lines

• Select from IC50 determination and single point concentrations

• Receive data within days of compound submission

• Perform follow-up studies using the same proteins manufactured in-house for greater reproducibility and consistency

• Design custom assays

• Conduct label-free BLI detection services for protein binding studies

• Get questions answered or project guidance in a time-efficient manner

Screening Assay Formats

Chemiluminescent Assay Kits

The Chemiluminescent Inhibitor Screening Assay Kits are designed for screening and profiling inhibitors. The key to these kits is the high sensitivity of detection of protein by Streptavidin-HRP. Only a few simple steps on a microtiter plate are required for the assay. The first protein is attached to a 96-well plate. Next, the second protein is incubated on the plate. Finally, the plate is treated with an HRP labeled protein followed by the addition of an HRP substrate to produce chemiluminescence, which then can be measured using a chemiluminescence reader.

Colorimetric Assay Kits

BPS Bioscience offers colorimetric assay kits to screen for inhibitors of Spike: ACE2 binding. In the assay protocol, the first protein is attached to a 96-well microtiter plate. Next, the test inhibitor compound or neutralizing antibody is added, followed by incubation of the second protein on the plate. Finally, the plate is treated with an HRP-labeled protein, followed by addition of an HRP substrate to produce color. The colorimetric response is measured using a UV/Vis spectrophotometer microplate reader.

Colorimetric IgG Detection Assay Kits

The SARS-CoV-2 IgG detection kits are designed for qualitative detection of human IgG antibodies in serum collected from individuals suspected of prior infection with the virus that causes . These fast and simple ELISA assays uses Spike proteins to identify IgG antibodies that recognize either the receptor binding domain (RBD) or the full-length, trimeric form of the Spike glycoprotein.

TR-FRET Assay Kit

The SARS-CoV-2 Spike S1:ACE2 TR-FRET Assay is designed to measure the inhibition of the binding between SARS-CoV-2 Spike S1 and human ACE2 in a homogeneous 96 or 384 reaction format. This TR-FRET-based assay requires no time-consuming washing steps, making it especially suitable for high throughput screening applications. The assay procedure is straightforward and simple; the test inhibitor compound is incubated with biotinylated Spike S1, Eu-labeled ACE2, dye-labeled acceptor and an inhibitor for one hour. Then the TR-FRET signal is measured using a fluorescence reader.

Fluorogenic Assay Kits

The fluorogenic assay kits are used for screening and profiling applications in a homogeneous assay with no time-consuming washing steps. The kits come in a convenient 96-well or 384-well format, including purified protein, fluorogenic substrate, assay buffer, and a known inhibitor for use as a positive control.

Homogeneous Assay Kit

The SARS-CoV-2 RdRp Homogeneous Assay Kit measures direct incorporation of ATP in the double-stranded RNA chain. The increase in Alpha-counts is proportional to the amount of ATP incorporated in the RNA.

Cell-Based Services

• Cell-based assays are available using the SARS-CoV-2 Spike-pseudovirus (79942) and the ACE2-HEK293 cell line (79951). This assay can be used to screen for neutralization of antibodies/small molecules which target the interactions between Spike and ACE2.

• Cell-based assays are also available using the Spike-pseudovirus (79942) and the TMPRSS2-Vero E6 cell line (78081). This assay can be used to screen for inhibitors of TMPRSS2 activity.

Lentiviruses

To understａnd the mechanism of SARS-CoV-2 cell entry, it is essential to study how Spike proteins interact with the ACE2 receptor. However, such studies are hampered by the danger of producing and manipulating live coronavirus. A safer alternative to using live coronavirus is to use recombinant lentivirus pseudotyped with the coronavirus S protein. The Spike pseudotyped lentivirus includes a luciferase reporter, allowing the monitoring of viral entry into host cells. BPS also offers the control (bald) lentivirus without Spike protein as well as ACE2 lentivirus to transduce cells for transient expression or to create stable cell lines as targets for the Spike pseudovirion. BPS offers a variety of SARS-CoV-2 related lentiviruses.

• Spike Lentiviruses

• Variant Lentiviruses

• Bald Lentiviruses

• ACE2 Lentivirus

• TMPRSS2 Lentivirus

Cell Lines

Custom Cell Line Development

CRISPR Services

With our CRISPR services in conjunction with our custom cell line development services, we can generate custom knock-out and knock-in cell lines using CRISPR/Cas9 licensed technology. The development process is comprised of five milestones, with data provided after completion of each milestone. Each project is customized for the desired deliverables while working directly with our team of highly trained scientists.

Protein Binding Studies/ Analytics with BLI Services

BPS Bioscience offers Bio-Layer Interferometry (BLI) services to evaluate and analyze protein interactions. Label free analysis is a critical research method to determine the binding kinetic parameters of compounds. These studies are of key importance for pharmaceutical and biotechnological preclinical drug development. Utilize BPS Biosciences’ BLI services for deeper insight into your protein studies through measuring binding kinetics, steady state affinity, and through target validation. BPS will provide accurate and sensitive kinetic studies in a timely manner to further progress your research.

Services offered include

• Protein immobilization

• Binding affinity measurements of experimental points

• Data fitting and reporting

• Access to BPS Bioscience’s extensive protein portfolio for target proteins

• A final report outlining all data, methods, and results

Contact us for more information about our protein binding studies and BLI services and to learn more about how BPS Bioscience can further progress your research.

Figure 1: BLI binding analysis of polyclonal human anti-ACE2 antibody to immobilized ACE2-His (BPS Bioscience #11003) via anti-His probes. Kd = 144 nM.

Figure 2: BLI binding analysis of SARS-CoV-2 Spike (RBD) to immobilized ACE2-His (BPS Bioscience #11003) via anti-His probes. Kd = 1.2 nM.

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