COVID-19

Engineering a Safer SARS-CoV-2 for Use in the Research Laboratory

Posted on by Sara Klink
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses such as SARS-CoV-2. Photo Credit: Alissa Eckert, MS; Dan Higgins, MAM CDC
SARS-CoV-2 illustration from CDC; Photo Credit: Alissa Eckert, MS; Dan Higgins, MAM
E = envelope; M = membrane

A worldwide pandemic requires scientific research to understand the viral pathogen. The focused efforts of global scientists are even more necessary in the face of a novel coronavirus like SARS-CoV-2, the causative agent of COVID-19. However, because SARS-CoV-2 causes human disease, research efforts are restricted by the need for physical laboratories that are equipped to handle the required level of containment and personnel trained to handle pathogens in these facilities. But what if we could bypass the restrictive facility requirements by engineering a synthetic, replication-defective version of SARS-CoV-2 that more researchers could use to study the pandemic coronavirus, expanding the capacity to test and develop methods to attenuate its devastating effect on humans?

The challenge is to develop a derivative of SARS-CoV-2 that reflects how it behaves in the cell but is compromised such that it is unable to infect cells more than a single time. That is, the virus can get into a cell or be introduced into cells and replicate but is unable to produce infectious virus would offer a pathway to expand research capacity without the use of special laboratory facilities. This replication-defective SARS-CoV-2 could be created to encode as much or as little of the genome needed to examine its lifecycle without becoming a fully infectious virus. In fact, this replication-defective version of SARS-CoV-2 could include additional genetic elements that could be used to control its expression, track the virus in cells and measure the level of its replication. This task has been undertaken by Dr. Bill Sudgen’s group at the University of Wisconsin–Madison McArdle Laboratory for Cancer Research, explained by graduate student Rebecca Hutcheson during her presentation “Making the Virus Causing COVID-19 Safe for Research”.

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Buckling Down to Scale Up: Providing Support Through the Pandemic

Posted on by Riley Bell

The past year has been a challenge. Amidst the pandemic, we’re thankful for the tireless work of our dedicated employees. With their support, we have continuously stayed engaged and prepared during all stages of the COVID-19 pandemic so that we can serve our customers at the highest levels.

How We Got Here

The persistent work by our teams has made a great impact on the support we can provide for scientists and our community during the pandemic. From scaling up manufacturing to investing in new automation, every effort has helped.

Promega has a long history of manufacturing reagents, assays, and benchtop instruments for both researching and testing viruses. When the pandemic began in 2020, we responded quickly and efficiently to unprecedented demands. In the past year, we experienced an approximately 10-fold increase in demand for finished catalog and custom products for COVID-19 testing. In response to these demands, we increased production lines. One year ago, we ran one shift five days per week. Currently, we run three shifts seven days per week. This change has allowed 50 different Promega products to support SARS-CoV-2 testing globally in hospitals, clinical diagnostic laboratories, and molecular diagnostic manufacturers. Additionally, our clinical diagnostics materials make up about 2/3 of COVID-19 PCR tests on the global market today. Since January 2020, Promega has supplied enough reagents to enable testing an estimated 700 million samples for SARS-CoV-2 worldwide.

Developments and Advances

Promega products are used in viral and vaccine research. This year, our technologies have been leveraged for virtually every step of pandemic response from understanding SARS-CoV-2 to testing to research studies looking at vaccine response.

Promega product: The Lumit™ Dx SARS-CoV-2 Immunoassay

Who Got Us Here

We are extremely grateful for our employees. In the past year, we hired over 100 people and still have positions open today. While welcoming newcomers, this challenging year also reinforced the importance of our collaborative culture. Relationships at Promega have been built over multiple years. The long history of our teams allows us to stay coordinated while prioritizing product distribution to customers across the globe. It also leads to effective communication with colleagues and vendors. Those leading our manufacturing operations team, for example, have an average tenure of 15 years. Their history in collaborating through challenging situations helps them quickly focus where needed most.

Our 600 on-site employees support product manufacturing, quality, and R&D. They do it all while remaining COVID-conscious by social distancing, wearing masks, working split shifts, and restricting movement between buildings. While we continue to practice physical safety precautions, we also prioritize our employees’ mental health and wellness. Promega provides a variety of wellness resources including phone and video mental health sessions, virtual fitness and nutrition classes, and stress and anxiety tools.

What’s to Come

While we acknowledge that the COVID-19 is not over, we are proud of the support we have been able to provide to customers working both on pandemic research and critical research not related to COVID-19. Our policies of long-term planning and investing in the future has allowed us to respond quickly and creatively and learn from the experience.

Related Posts

How to Train Your Instrument Service Team in a Pandemic

Posted on by Darcia Schweitzer
Service engineers engaged in remote instrument training.

When the Spectrum Compact CE System launched in June 2020, all the instrument service engineers that are part of the Promega Global Service & Support (GSS) Team needed to be trained on using and fixing the instrument. This is a challenging endeavor in the best of times, but the COVID-19 pandemic made it even more difficult. Thanks to the work of some dedicated teams and individuals, Promega service engineers around the world were able to receive remote instrument training. But how do you teach someone to repair an instrument when you can’t be in the same room?

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Intranasal COVID-19 Vaccines: What the Nose Knows

Posted on by Ken Doyle

COVID-19 vaccine distribution efforts are underway in several countries. Recently, the Serum Institute of India celebrated the nationwide rollout of its Covishield vaccine, kicking off the country’s largest ever vaccination program. Meanwhile, many other vaccines against the coronavirus that causes COVID-19 are in either preclinical studies or clinical trials. At present, 19 vaccine candidates are in Phase 3 clinical trials, while 8 vaccines have been granted emergency use authorization (EUA) in at least one country.

intranasal covid-19 vaccine coronavirus

In the US, mRNA vaccines from Pfizer/BioNTech and Moderna are in distribution. Adenoviral vector vaccines authorized for distribution include Oxford/AstraZeneca AZD1222 in the UK (Covishield in India) and Gamaleya Sputnik V in Russia. A third type of vaccine consists of inactivated coronavirus particles, such as those developed by Sinopharm and Sinovac in China.

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Adenoviral Vector Vaccines for COVID-19: A New Hope?

Posted on by Ken Doyle

The global war against the coronavirus that causes COVID-19 rages on, spearheaded by efforts to develop effective and safe vaccines. At the time of writing, over 100 COVID-19 vaccine clinical trials were listed in the clinicaltrials.gov database. Recent attention has focused on mRNA vaccines developed by Pfizer/BioNTech and Moderna. If licensed, they would become the first mRNA vaccines for human use.

Other vaccine development efforts are relying on more conventional techniques—using an adenoviral vector to deliver a DNA molecule that encodes the SARS-CoV-2 spike (S) protein. Examples of these adenoviral vector vaccines include the vaccines from Oxford University/AstraZeneca (the UK), Cansino Biologics (China), Sputnik V (Russia) and Janssen Pharmaceuticals/Johnson & Johnson (the Netherlands and USA).

sars-cov-2 coronavirus covid-19 infection with antibodies from a vaccine attacking the virus; several vaccines are in development including adenoviral vector vaccines
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Automation Helps A Graduate Student Monitor COVID-19 With Wastewater

Posted on by Johanna Lee
Kasia Slipko (middle) and her lab at Vienna University of Technology. She and colleagues are exploring using wastewater to monitor viral disease outbreaks.
Kasia Slipko (middle) and her lab at Vienna University of Technology. She and colleagues are exploring using wastewater to monitor viral disease outbreaks.

When Kasia Slipko started graduate school at Vienna University of Technology, Institute for Water Quality and Resource Management, she was interested in studying antibiotic resistant microbes in wastewater. For three years, she evaluated different wastewater treatment methods to find out how to remove antibiotic resistant bacteria. But in the spring of 2020, her research took an unexpected turn. That was when the COVID-19 global pandemic hit, caused by the rapid spread of the SARS-CoV-2 virus. Kasia soon found herself at the forefront of another exciting field: using wastewater to monitor viral disease outbreaks.

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Adapting Holiday Traditions: COVID, Customs and Cookies at Promega

Posted on by Karen Burkhartzmeyer

Adaptation: In biology and ecology, the process or state of adjusting or changing to become more suited to an environment.    

Holiday traditions are certainly taking new forms this year as we all determine how to safely celebrate during a pandemic. It goes without saying that it’s been a tough year. Customs and rituals, large and small, bring peace and comfort. We need those more than ever now, so the challenge becomes finding new ways to honor valued traditions.

Chuck York, VP Manufacturing delivers individually packaged cookies to R&D Scientists on the Promega Madison Campus, adapting this holiday tradition to the life during a pandemic.
This year’s cookie delivery happened with a twist. Chuck York, VP Manufacturing delivers individually packaged cookies to R&D Scientists on the Promega Madison Campus.

Today, we would like to share how one dearly held Promega Madison tradition was able to endure in our COVID-19 world. Adaptation is key. And butter and sugar help, too.

Elaine Day

Promega employees this week were surprised and deeply moved to find that their beloved “Elaine Day” had not become yet another casualty of the pandemic.

“This has been such a difficult year,” says Senior QA Scientist Sue Wigdal. “I had assumed, sadly, that Elaine Day would be cancelled, but to be able to have it and all the thoughtfulness and deliciousness that it brings, was amazing.”  

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SARS-CoV-2 Nucleocapsid Protein and PA28γ: A Role in Pathogenesis?

Posted on by Gary Kobs

The SARS-CoV-2 nucleocapsid protein accounts for the largest proportion of viral structural proteins and is the most abundant protein in infected cells. Nucleocapsid proteins have the job of “packaging” the viral nucleic acid (in this case, RNA). Viral nucleocapsid proteins can also enter the host nucleus and interact with a variety of host proteins to interfere with critical processes of the host cell, including protein degradation. Here we review a study that used an in vitro protein degradation assay to investigate the interaction of the SARS-CoV-2 nucleocapsid protein and the proteasome activator PA28γ.

SARS-CoV-2 structural diagram, showing the SARS-CoV-2 nucleocapsid protein composed of RNA and N protein.

In SARS-CoV-2 infections, the nucleocapsid protein is critical for infection, replication and packaging. The SARS-CoV-2 nucleocapsid protein is not only localized in the cytosol of the host cell but also is translocated into the nucleus. There, it interacts with various cellular proteins that modulate cellular functions, such as the degradation of unneeded or damaged proteins by proteolysis. Researchers have proposed that the protein degradation system plays an important part in coronavirus infection (1).

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Non-Respiratory Symptoms of COVID-19

Posted on by Jordan Villanueva

The truth is that much of what we were told in the early days of the COVID-19 pandemic was not entirely accurate. Many of the messages in the United States and other countries implied that the disease was “mild” for anyone who was not elderly or did not have a pre-existing respiratory condition. We were told the main symptoms were fever, coughing and difficulty breathing. It would be like a bad cold.

None of that is false. Data still shows that elderly individuals and those with pre-existing conditions are the most likely to experience severe disease. However, over the past few months we have seen how the SARS-CoV-2 virus can present serious complications in almost every organ system, and how its effects aren’t limited to the most vulnerable populations. We have also seen a growing number of cases where individuals are still experiencing life-altering symptoms for months after their supposed recovery.

To gain a full understanding of SARS-CoV-2 and COVID-19, we have to explore every system in the body and track down the causes of all the unexpected clinical presentations of the disease.  

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mRNA Vaccines for COVID-19: The Promise and Pitfalls

Posted on by Ken Doyle

Updated 8/25/2021, 4/29/2024

Multiple battles are being fought in the war against the SARS-CoV-2 coronavirus that causes COVID-19. Currently, there are nearly 5,000 clinical trials listed in the World Health Organization (WHO) database, either underway or in the recruiting stage, for vaccines and antiviral drugs. The Moderna mRNA vaccine and Janssen vaccine received emergency use authorization (EUA) from the Food and Drug Administration (FDA) and have since been fully approved; the Pfizer-BioNTech Vaccine (marketed as Comiraty) received FDA approval in August 2021.

mrna vaccines and coronavirus covid-19

Both the Moderna vaccine and Comiraty are mRNA-based, as opposed to most conventional vaccines against established diseases that are protein-based. Typically, the key ingredient in viral vaccines is either part of an inactivated virus, or one or more expressed proteins (antigens) that are a part of the virus. These protein antigens are responsible for eliciting an immune response that will fight future infection by the actual virus. Another approach is to use a replication-deficient viral vector (such as adenovirus) to deliver the gene encoding the antigen into human cells. This method was used for the coronavirus vaccine developed by Oxford University in collaboration with AstraZeneca; phase 3 interim data were announced on the heels of the Pfizer/BioNTech and Moderna announcements. All three vaccines target the SARS-CoV-2 spike protein, because it is the key that unlocks a path of entry into the host cell.

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