Every time a genome is replicated, there’s a chance that an error will be introduced. This is true for all life forms. On a small scale, these mutations can lead to genetic diseases or cancers. On a much larger scale, random mutations are an important tool of evolution.
During the COVID-19 pandemic, the SARS-CoV-2 virus has picked up many mutations as it spread around the world. Most of these mutations have been inconsequential – the virus didn’t change in any significant way. Others have given rise to variants such as B.1.1.7 and B.1.351, which present complications for public health efforts. By studying the evolution of the virus, we can monitor how it’s spreading and predict the characteristics of variants as they are detected.
A year after COVID-19 was declared a pandemic, collaborative efforts among pharma/biotech and academic researchers have led to remarkable progress in vaccine development. These efforts include novel mRNA vaccine technology, as well as more conventional approaches using adenoviral vectors. While vaccine deployment understandably has captured the spotlight in the fight against COVID-19, there remains an urgent need to develop therapeutic agents directed against SARS-CoV-2.
In the March 12 issue of Science, an editorial by Dr. Francis Collins, director of the U.S. National Institutes of Health (NIH), examines lessons learned over the past 12 months (1). Collins points out that many clinical trials of potential therapeutics were not designed to suit a public health emergency. Some were poorly designed or underpowered, yet they received considerable publicity—as was the case with hydroxychloroquine. Collins advises developing antiviral agents targeted at all major known classes of pathogens, to head off the next potential pandemic before it becomes one. A news feature in the same issue discusses the current state of coronavirus drug development (2).
The present crop of drug candidates is remarkably diverse, including repurposed drugs that were originally developed to treat diseases quite different from COVID-19. Typically, however, the mainstream candidates belong to two broad classes: small-molecule antiviral agents and large-molecule monoclonal antibodies (mAbs).
Small- and medium-sized companies are critical to the Spanish economy. During 2020 the COVID-19 pandemic made business difficult for many of these companies, yet they have demonstrated strength and resourcefulness and have led the pandemic recovery in Spain in many ways. Recently, Promega Biotech Ibérica was recognized with a Madrid Community SME (small- and medium-sized business) Award along with 15 other companies. The awards were presented by Manuel Giménez, Minister of Economy, Employment and Competitiveness of the Madrid Region, Andres Navarro delegate director of La Razón, and Francisco Marhuenda, director of La Razón. As part of the award, Promega Biotech Ibérica General Manager, Gijs Jochems, was interviewed about the award and Promega’s work in the region.
According to Gijs Jochems, General Manager of Promega Biotech Ibérica, while Promega Corporation is an American multinational company, it remains privately held, which offers a great deal of flexibility to the subsidiaries to adapt to local needs. It also allows the company to place increased emphasis on employee well-being (critical during the pandemic), reinvest profits in research and development, and work to mitigate the impact of company activities on the environment. All these business practices reflect a long-term vision of sustainable business growth.
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”.
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.
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.
When you look at our top 10 most viewed blog posts of 2020, there’s no surprise that all relate to COVID-19. We have come a long way since the beginning of the year, thanks to tireless scientists and researchers around the globe. They have led the way in COVID-19 research, treatment, and testing. Let’s take a closer look at this top 10 list:
10. Tips to Maintain Physical Distance in the Lab
The spread of COVID-19 forced us to adapt and adjust to new ways in life, in work, and for this blog post, in the lab. In response to the pandemic, some labs shut down completely. Others have stayed open, especially those involving coronavirus research. This post provides 10 helpful distancing tips for researchers to stay safe and productive while working in the lab.
9. Investigation of Remdesivir as a Possible Treatment for SARS-2-CoV (2019 nCoV)
Scientists have worked hard to determine possible treatment for COVID-19. This blog post focuses on Remdesivir (RDV or GS-5734), an encouraging treatment used for the first case in the United States. It provides an in-depth look at numerous studies and clinical trials on Remdesivir as treatment for COVID-19. One key finding is that RDV needed to be administered either before or shortly after infection to limit lung damage.
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.
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.
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.
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).
The fall of 2020 was like no other, especially for universities. The COVID-19 pandemic hit most of the world in the spring, forcing schools and businesses to close. For months, people worked from home and schools switched to online classes. When fall came, universities had a difficult decision to make. Do they have students and staff come back to campus for in-person classes? With students living together in close proximity in dormitories, an outbreak could quickly get out of hand. How can the university monitor and control the spread of the virus to ensure everyone’s safety?
This was when Robert Brooks started getting calls. He’s the Technical Director and Operations Manager at Microbac Laboratories in Oak Ridge, Tennessee. Microbac is a network of privately owned laboratories that provide testing services for food products, environmental samples and the life science industry. Robert has been in the lab industry for 25 years and has established a reputation for taking on difficult problems. “We really try to go that extra mile to help clients solve their issues. That has made a name for us out there. When people have odd-ball issues, they give us a call cause we’re going to take a look at it from a couple different viewpoints and take a step-by-step approach,” he says.