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SARS-CoV-2 Research, Vaccine and Therapeutic Development

In addition to the need for fast development of assays to detect SARS-CoV-2 and identify exposed individuals, the COVID-19 crises has led to massive worldwide efforts to develop drug treatments and vaccines effective against SARS-CoV-2. A more comprehensive understanding of the biology of the SARS-CoV-2 virus is also needed. We support scientists working to develop vaccines and to answer questions about viral pathology and treatment including:

  • How does the virus enter human cells?
  • How does the virus make people sick?
  • What treatments can be used to alleviate symptoms?
  • How can immunity to the virus be gained?

We offer collaborative support and a broad portfolio of reagents that are used in research labs studying coronaviruses and other emerging viral diseases.

Tracking and Monitoring Viral Activity in Cells

Understanding the interactions between viral pathogens and host cells, and monitoring the effect of viral activity on cells, are essential to the development of effective anti-viral treatments or vaccines. Promega technologies are used in studies monitoring key steps in viral pathogenesis, including detecting virus interactions with host cell surface receptors, tracking and monitoring production of viral nucleic acids and proteins within the cell, and monitoring host cell viability and metabolism.


Detect Virus:Host Protein:Protein Interactions

Understanding how the SARS-CoV-2 virus enters host cells is a potential first step to developing a treatment or preventing infection. Viral entry is dependent on protein:protein interactions between a host cell surface receptor and the viral proteins. Protein:protein interaction assays are a valuable tool for studying these interactions.

NanoBiT? and NanoBRET? technologies provide the sensitivity necessary to detect protein:protein interactions at the concentrations expressed in vivo.  Both are bioluminescence-based methods that are particularly useful in viral studies due to the small size and bright signal of the luciferase used. For more details, see the references and resources below.

NanoLuc technologies applied to virology

Reporter technologies are creating ways to study virus:host interactions in more detail than ever before.

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NanoBRET Technology Introduction

Machleidt, T., et al. (2015) NanoBRET–A novel BRET platform for the analysis of protein-protein interaction. ACS Chem. Biol. 10, 1797-804.

NanoBiT Technology Introduction

Track Recombinant Viruses and Detect Reporter Activity

Luciferase reporters provide a simple and convenient method for monitoring the effect of potential treatments, creating in vitro assays for detecting viral antibodies, and for imaging viruses in animal models. The small size of NanoLuc® Luciferase is especially useful for the creation of reporter viruses.

Other reporters, including firefly and Renilla luciferase, are often used in the creation of pseudotyped viruses. Pseudotyped virus particles are made by replacing the host-binding protein with a host-binding protein of another virus and adding a genetic reporter, allowing researchers to study the viral entry process. Pseudotyped viruses are also used to study inhibitors of the virus, such as antibodies and small molecule compounds.

Remdesivir as a potential treatment for SARS-CoV-2

This blog highlights use of reporter viruses to study the effectiveness of the antiviral agent Remdesivir.
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Pseudovirus studies using reporter assays
Use of pseudovirus to study receptor binding

Walls, A.C., et al. (2020) Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell  online 9 March 2020.


Andersen, P.I. (2020) Discovery and development of safe-in-man broad-spectrum antiviral agents. Int. J. Inf. Dis. 93, 268-75. 

Advantages of a small, bright luciferase reporter

Recombinant reporter viruses are important tools for furthering our understanding of viral life cycles and lethality in cell and animal models. Reporter viruses make it easier to follow infection in the same animal over time and quantify events such as cellular entry and replication.

Insertion of large reporter genes (e.g., firefly luciferase) into the genome often causes defects in viral processes. Because of their small size, NanoLuc? and HiBiT tags can be stably inserted into the viral genome without disrupting the natural biology of the virus.

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Detect and Monitor Viral Copy Number

PCR-based methods, such as endpoint and real-time PCR and RT-PCR, are fundamental tools used in the development of viral detection tests, and for analysis of viral genomes.

GoTaq® PCR and qPCR systems and GoScript™ Reverse Transcriptase offer robust and reproducible amplification and reverse transcription for detecting and amplifying sequences for numerous viral targets. 

The GoTaq® 1-Step RT-qPCR System is approved for use with CDC protocol for SARS-CoV-2 Detection. PCR Master Mix has also been used in the development of a SARS-CoV-2 PCR diagnostic test.  

CDC SARS-CoV-2 Test Protocol

The GoTaq® 1-Step Probe system is an option for use with the Novel Coronavirus Real-Time RT-PCR Diagnostic Panel.
View protocol


GoTaq? 1-Step RT-qPCR System

Nelson, A.C. et al.  (2020) Analytical Validation of a COVID-19 qRT-PCR Detection Assay Using a 384-well Format and Three Extraction Methods. doi: https://doi.org/10.1101/2020.04.02.022186

Driouich, J.-S., et al. (2018) SuPReMe: A rapid reverse genetics method to generate clonal populations of recombinant RNA viruses. EmergMicrob. Infect. 7, 40

Viral Structure and Characterization

Monitor Host Cell Function

Monitoring compounds for antiviral activity includes testing for viral-induced cytopathic effects (CPE) in host cells. A viability assay amenable to high-throughput analysis such as CellTiter-Glo? is useful for testing hundreds or thousands of compounds at once, reducing the time needed to analyze the effect of potential treatments. Viability assays are also used to support studies investigating the mechanism of action of viruses. 

In addition to cytopathic effects, viral infection induces changes in cellular metabolism. In many infectious diseases, viruses reprogram host cell metabolism to support viral replication. These virus-induced metabolic changes can be understood using assays that monitor nutrient uptake and changes in co-factors such as NADPH, among others.

Characterization of proteins by mass spectrometry is another approach used to monitor virus-induced changes in host cells. Analysis of changes in cellular proteins helps researchers understand how viruses interact with cellular pathways.

How the coronavirus enters cells and how to block it

Read about viral host interactions, and how cell viability assays support these studies.

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Evaluation of SARS-CoV-2 inhibitors using cell viability assay
Overview of SARS-CoV-2 metabolic impact

Bornstein, S. et al. (2020) Endocrine and metabolic link to coronavirus infection. Nat. Rev. Endocrinol.   https://www.nature.com/articles/s41574-020-0353-9

Proteomics in SARS-CoV-2 infection

Bojkova, D. et al. (2020)SARS-CoV-2 infected host cell proteomics reveal potential therapy targets. DOI: 10.21203/rs.3.rs-17218/v1 Accessed April 17, 2020.

Monitor Immune Response

A key question asked by viral researchers is how a host’s immune system responds to the viral infection, including both adaptive and innate immunity. The innate immune response involves activation of inflammasomes and cytokine release. While this cytokine release is therapeutic, a “cytokine storm” can be an adverse side effect in patients that must be managed with additional therapeutics designed to block the efficacy of the released cytokines such as IL-6 and IL-15.

In addition to the innate immune response, humoral and cellular responses play key roles in host response. These questions can be answered with reporter bioassays as well as assays to detect the activity of caspase-1 and levels of cytokines in cell-based research applications.

The Cytokine Storm

Why the host immune response makes some COVID-19 cases more severe.

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Inflammasome activation in viral infection

Soderholm, S. et al. (2016) Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages (2016) Molecular & Cellular Proteomics 15(10), 3203–3219.

Inflammasome activation in SARS-CoV-2 infection

Conti P. et al. (2020) Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (CoV-19 or SARS-CoV-2): anti-inflammatory strategies. J. Biol. Regul. Homeost. Agents Mar 14; 34(2) doi: 10.23812/CONTI-E [Epub ahead of print].

Use of a reporter bioassays to study neutralizing antibodies

Pinto, D., et al. (2020) Structural and functional analysis of a potent sarbecorvirus neutralizing antibody. bioRxiv posted 9 Apr 2020.

RNA Production for Vaccine Research and Development

Transcribed RNA is required for vaccine production, viral standards, and basic viral research. For in vivo and in vitro studies, RiboMAX® RNA Production System generates a large quantity of high-quality RNA or mRNA  from a DNA template without the need for mammalian cells or cell components. These in-vitro transcribed viral RNA or mRNA transcripts, typically encoding a disease-specific antigen such as the spike protein of a coronavirus, may be used as inoculation material for viral infection studies. If the transcribed mRNA is to be used as a therapeutic, the mRNA encoding a desirable protein can be packaged as necessary for delivery to the tissue of interest.


Generation of Coronavirus RNA

Eriksson K.K., et al. (2008) Generation of Recombinant Coronaviruses Using Vaccinia Virus as the Cloning Vector and Stable Cell Lines Containing Coronaviral Replicon RNAs. In: Cavanagh D. (eds) SARS- and Other Coronaviruses. Methods in Molecular Biology (Methods and Protocols), vol 454. Humana Press, Totowa, NJ. 

RNA preparation
Standard RNA production with RiboMAX

Xu, L. et al. (2009) Evaluation of Sensitivities and Specificities of SARS-CoV Detection by Real-Time Quantitative Reverse Transcription-PCR Assays. Virologica Sinica, 24 (3), 187-193. DOI 10.1007/s12250-009-3021-8 

Bioluminescence Detection

The bioluminescence technology used in Promega reagents for viral research make the assays highly sensitive and simple to use. GloMax® plate-readers come with pre-loaded protocols that make reading and interpreting results from Promega luminescence assays even simpler. 

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