COVID-19

Virus-Like Particles: All the Bark, None of the Bite

Posted on by Ken Doyle

Globally, there have been over 5 million deaths attributed to COVID-19 since the start of the pandemic. Throughout the ongoing battle against SARS-CoV-2, researchers have been studying the viral lineage and the variants that are emerging as the virus evolves over time. The more opportunities that the virus has to replicate (i.e., the more people it infects), the greater the likelihood that a new variant will emerge.

This short video from the World Health Organization explains how viral variants develop.

The US Centers for Disease Control and Prevention (CDC) classify SARS-CoV-2 variants into four groups: Variants Being Monitored (VBM), Variants of Interest (VOI), Variants of Concern (VOC) and Variants of High Consequence (VOHC). So far, no variants in the US have been identified as VOHC or VOI. Currently, the most common variant in the US is the Delta variant (which includes the B.1.617.2 and AY viral lineages), and it is classified as a VOC.

The Delta variant originated in India and spread rapidly across the UK before making its way into the US (1). Current vaccines, including mRNA and adenoviral vector vaccines, have demonstrated effectiveness against the Delta variant. However, it is a VOC because it is more than twice as contagious as previous variants, and some studies have shown that it is associated with more severe symptoms.

A recent study (2) provides one explanation for the higher infectivity of the Delta variant, using an approach based on virus-like particles (VLPs). The research team was led by Dr. Jennifer Doudna, 2020 Nobel Prize winner for her work on CRISPR-Cas9 gene editing, and Dr. Melanie Ott, director of the Gladstone Institute of Virology at the University of California–Berkeley.

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New Assay to Study SARS-CoV-2 Interaction with Human ACE2 Receptor

Posted on by Promega

Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus. The most recent version, SARS-CoV-2 was first detected in China in the winter of 2019 and is responsible for the current COVID-19 (coronavirus disease 2019) global pandemic. This virus and its variants have resulted in over 200 million infections and more than 4 million fatalities world-wide. To combat this deadly outbreak the global research community has responded with remarkable swiftness with the development of several vaccines and drug therapies, all produced in record time. In addition to vaccines and drug therapies, diagnostic kits and research reagents continue to roll out to track infections and to help find additional therapies.

This peer-reviewed paper published in Nature Scientific Reports by Alves and colleagues demonstrates how a new assay can be used to discover novel inhibitors that block the binding of SARS-CoV-2 to the human ACE2 receptor as well as study how mutations in the SARS-CoV-2 Spike protein alter its apparent affinity towards human ACE2. The paper also details studies where the assay is used to detect the presence of neutralizing antibodies from both COVID-19 positive samples as well as samples from vaccinated individuals.

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What You Should Know About The Delta Variant

Posted on by Jordan Villanueva

The Delta Variant poses a unique challenge to global health. We’ve compiled answers to some of the most common questions about Delta and other SARS-CoV-2 variants.

What is a variant?

A variant is a form of a virus that is genetically distinct from the original form.

“All organisms have mutation rates,” says Luis A Haddock, a graduate student at University of Wisconsin – Madison. “Unfortunately for us, viruses have one of the highest mutation rates of everything that currently exists. And even more unfortunately, RNA viruses have the highest mutation rates even among viruses.”

Luis works in the Friedrich Lab at UW-Madison, which has been sequencing SARS-CoV-2 genomes from positive test samples since the beginning of the pandemic. SARS-CoV-2 is constantly evolving, and sequencing can help us follow it through time and space. Most of the variants don’t behave any differently. A single nucleotide substitution might not even change the amino acid sequence of an encoded protein. However, occasionally a mutation will alter the structure or function of a protein.

Learn more about SARS-CoV-2 sequencing in the article “From Primate Models to SARS-CoV-2 Sequencing and Testing,” featuring David and Shelby O’Connor, two collaborators of the Friedrich Lab.

What is a Variant of Concern?

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Two COVID-19 Waves in Brazil Driven by Separate Lineages of SARS-CoV-2

Posted on by Jordan Villanueva

The Brazilian state of Amazonas experienced two distinct waves of COVID-19 infections in 2020. After the first wave, a team from the University of Sao Paolo projected that the city of Manaus would reach the theoretical threshold for herd immunity by the end of the summer. However, a second COVID-19 wave erupted in December 2020, coinciding with the rise of Variant of Concern (VOC) P.1.

3d model of coronavirus covid-19

New research published in Nature Medicine examined the different lineages of COVID-19 present in Brazil over time and determined that the two waves were driven by different variants. The first wave was driven by the variant B.1.195, which was imported from Europe in the spring. The second wave was largely driven by VOC P.1. The Nature Medicine study is the first to use viral sequences from samples collected throughout 2020 to explore the epidemiological and virological factors behind the two distinct COVID-19 waves.

Detecting VOC P.1 in Amazonas Samples

The researchers started by generating whole-genome sequences of 250 SARS-CoV-2 samples collected between March 2020 and January 2021. The survey showed that 20% of the sequences belonged to the B.1.195 lineage, and these mostly corresponded with the first exponential growth phase. 24% of the samples belonged to the P.1 lineage, and all of these samples corresponded with the rise of the second exponential growth phase. The largest share belonged to B.1.1.28 (37%), which replaced B.1.195 as the dominant variant in Brazil shortly after the first wave until the rise of VOC P.1.

The team also used real-time RT-PCR to analyze 1,232 positive samples collected in Amazonas between November 1, 2020 and January 21, 2021. The assay was designed to detect a deletion in NSP6, which is a signature mutation of VOC P.1. None of the samples collected before December 16 showed the NSP6 deletion, but it was common in samples starting in mid-December. Combining the two analysis methods, the team found the P.1 lineage in 0% of samples collected in November 2020, but by January 1-15 it was present in 73.8% of samples.

This data supports the theory that VOC P.1 first emerged in December 2020 and was the dominant lineage driving the second wave in Amazonas.

Two COVID-19 Waves: Virological and Epidemiological Factors

In addition to tracking the prevalence of lineages throughout the pandemic, the researchers also offered suggestions for how Amazonas experienced two distinct waves of COVID-19 infections.

Using computer modeling, the team found a significant reduction in reproductive efficiency (Re) of lineages B.1.195 and B.1.1.28 in April-May 2020, around the same time that Amazonas increased social distancing measures. Transmission rates remained low until the interventions were relaxed in September 2020. This suggests that the reduction in cases was not a result of herd immunity. Instead, nonpharmaceutical interventions (NPI) limited the first wave and contained the spread through the summer.

Using real-time RT-PCR, the researchers found that the viral load of P.1 infections was nearly ten times the viral load of non-P.1 infection. They also referenced other research that found that VOC P.1 has a stronger affinity for the human receptor ACE2 than B.1.195 and B.1.1.28. P.1 is clearly a highly transmissible VOC, and it evolved in an ideal environment for rapid spread. Amazonas had relaxed social distancing measures by late 2020, P.1 was able to quickly reach extremely high infection rates.

The study did not directly address theories that P.1 evades immunity developed from prior infections, but they concluded that a combination of epidemiological and virological factors allowed P.1 to drive a second wave of COVID-19 in Amazonas starting in December.

The paper includes a supplementary note suggesting that NPIs instituted in Manaus in January 2021 significantly reduced transmission rates of VOC P.1. The team ends the paper by reiterating the importance of adequate social distancing measures to limit the spread of COVID-19 and prevent the emergence of new Variants of Concern.

Read the entire paper here.

This study used the Maxwell® RSC Viral Total Nucleic Acid Purification Kit to extract viral RNA from samples. Learn more about the kit and its uses during the COVID-19 pandemic here.

Understanding Inflammation: A Faster, Easier Way to Detect Cytokines in Cells

Posted on by Johanna Lee

Inflammation, a process that was meant to defend our body from infection, has been found to contribute to a wide range of diseases, such as chronic inflammation, neurodegenerative disorders—and more recently, COVID-19. The development of new tools and methods to measure inflammation is crucial to help researchers understand these diseases.

This diagram shows how the Lumit™ Immuno assay can be used to detect cytokines.

Cytokines—small signaling molecules that regulate inflammation and immunity—have recently become the focus of inflammation research due to their role in causing severe COVID-19 symptoms. In these severe cases, the patient’s immune system responds to the infection with uncontrolled cytokine release and immune cell activation, called the “cytokine storm”. Although the cytokine storm can be treated using established drugs, more research is needed to understand what causes this severe immune response and why only some patients develop it.

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What Is A Viral Variant?

Posted on by Jordan Villanueva

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.

SARS-CoV-2 variant
David Goodsell Painting of SARS-CoV-2 Virus
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COVID-19 Therapies: Are We There Yet?

Posted on by Ken Doyle

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.

COVID-19 therapeutic drugs

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).

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Promega Biotech Ibérica Earns Recognition for Contributions to the COVID-19 Pandemic Response in Spain

Posted on by Promega

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.

Gijs Jochems, General Manager of Promega Biotech Ibérica accepts the Madrid Community SME Award.
Gijs Jochems, General Manager of Promega Biotech Ibérica accepts the Madrid Community SME Award.

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.

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From Primate Models to SARS-CoV-2 Sequencing and Testing

Posted on by Jordan Villanueva

As the SARS-CoV-2 virus spread around the world in early 2020, many researchers shifted their focus to support the global endeavors to address the challenge. For two professors at the University of Wisconsin, their efforts started with animal models to study pathogenicity and grew into massive SARS-CoV-2 sequencing and COVID-19 testing projects.

Virologists David and Shelby O'Connor (shown running along Lake Mendota) have worked extensively in SARS-CoV-2 Sequencing and COVID-19 Testing

“Being a scientist in this field gives a sense of purpose, but also a sense of obligation and responsibility,” says David O’Connor, PhD. “You always want to feel like you’re living up to that.”

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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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