In the Literature

Blogs about published peer-reviewed scientific studies.

Neutralizing Antibodies to SARS-CoV-2 Shown to Lessen Infection in Mice

Posted on by Kari Kenefick

Here in the US, as around the world, we’re beginning to come out of COVID-19 hiding, whether mandated or voluntary. We are slowly starting to leave the confines of home and “safer at home” orders. Many of us are donning masks and venturing out as needed, still under social distancing considerations.

We’re looking forward to a time when social distancing won’t be necessary, when we can see our relatives and friends, and give them a hug without concern for their safety or ours.

When will that time come? Many believe that it won’t be completely safe until there is an effective vaccine to protect us from SARS-CoV-2.

How does a vaccine protect us? Effective vaccines cause our immune system to produce antibodies that are specific for SARS-CoV-2, so that if we come into contact with the virus, it will be neutralized, preventing infection.

At this time, many questions remain about whether SARS-CoV-2 virus causes production of antibodies. And if antibodies are produced, are they protective?

In some exciting news this week, scientists studying SARS-CoV-2 have shown that neutralizing antibodies to this virus are made in humans. Here’s a look at their work.

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Illuminating the Function of a Dark Kinase (DCLK1) with a Selective Chemical Probe

Posted on by Promega

The understudied kinome represents a major challenge as well as an exciting opportunity in drug discovery. A team of researchers lead by Nathanael Gray at the Dana Farber Cancer Institute was able to partially elucidate the function of an understudied kinase, Doublecortin-like kinase 1 (DCLK1), in pancreatic ductal adenocarcinoma cells (PDAC). The characterization of DCLK1 in PDAC was realized by developing a highly specific chemical probe (1). Promega NanoBRET™ Target Engagement (TE) technology enabled intracellular characterization of this chemical probe.

The Dark Kinome

NanoBRET target engagement

Comprised of over 500 proteins, the human kinome is among the broadest class of enzymes in humans and is rife with targets for small molecule therapeutics. Indeed, to date, over 50 small molecule kinase inhibitors have achieved FDA approval for use in treating cancer and inflammatory diseases, with nearly 200 kinase inhibitors in various stages of clinical evaluation (2). Moreover, broad genomic screening efforts have implicated the involvement of a large fraction of kinases in human pathologies (3). Despite such advancements, our knowledge of the kinome is limited to only a fraction of its family members (3,4). For example, currently less than 20% of human kinases are being targeted with drugs in clinical trials. Moreover, only a subset of kinases historically has garnered substantial citations in academic research journals (4). As a result, a large proportion of the human kinome lacks functional annotation; as such, these understudied or “dark” kinases remain elusive to therapeutic intervention (4).

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RiboMAX and the Effort to Find Antiviral Drugs to Fight Coronaviruses and Enteroviruses

Posted on by Promega

Prior to 2020, there were two major outbreaks of coronaviruses. In 2003, an outbreak of SARS-CoV sickened 8098 people and killed 774. In 2012, an outbreak of MERS-CoV began which so far has sickened 2553 and killed 876. Although the overall number of MERS cases is low, the disease has a high fatality rate, and new cases are still being reported. Even though fatality rates are high for these two outbreaks, containment was quickly achieved. This makes development of a treatment not commercially viable so no one had undertaken a large effort to develop an approved treatment for either coronavirus infection.

Fast forward to late 2019/2020… well, you know what has happened. There is currently no reliable antiviral treatment for SARS-CoV-2, the coronavirus that causes COVID-19 infections.

Zhang, et al. thought of a way to make an antiviral treatment commercially viable. If the treatment is actually a broad-spectrum antiviral, it could be used to treat more than one infection, meaning, it can be used to treat more people and thus be seen as more valuable and worth the financial risk to pharmaceutical companies. So, they decided to look at the similarities between coronaviruses and enteroviruses.

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RT-qPCR and qPCR Assays—Detecting Viruses and Beyond

Posted on by Kelly Grooms

We have all been hearing a lot about RT-PCR, rRT-PCR and RT-qPCR lately, and for good reason. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) is the technique used in by the Center for Disease Control (CDC) to test for COVID-19. Real-time RT-PCR, or quantitative RT-PCR (RT-qPCR)*, is a specialized PCR technique that visualizes the amplification of the target sequence as it happens (in real-time) and allows you to measure the amount of starting target material in your reaction. You can read more about the basics of this technique, and watch a webinar here. For more about RT-PCR for COVID-19 testing, read this blog.

Both qPCR and RT-qPCR are powerful tools for scientists to have at their disposal. These fundamental techniques are used to study biological processes in a wide range of areas. Over the decades, Promega has supported researchers with RT-qPCR and qPCR reagents and systems to study everything from diseases like COVID-19 and cancer to viruses in elephants and the circadian rhythm of krill.  

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Which Came First: The Virus or the Host?

Posted on by Ken Doyle

They existed 3.5 billion years before humans evolved on Earth. They’re neither dead nor alive. Their genetic material is embedded in our own DNA, constituting close to 10% of the human genome. They can attack most forms of life on our planet, from bacteria to plants to animals. And yet, if it wasn’t for them, humans might never have existed.

3D structure of a coronavirus, viral evolution
A depiction of the shape of coronavirus as well as the cross-sectional view. The image shows the major elements including glycoproteins, viral envelope and helical RNA. This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.

No, that’s not the blurb for a new Hollywood blockbuster, although recent developments have proven, once again, that truth is decidedly more bizarre than fiction. Now that “coronavirus” has become a household word, the level of interest in all things virus-related is growing at an unprecedented rate. At the time of writing, coronavirus and COVID-19 topics dominated search traffic on Google, as well as trends on social media. A recent FAQ on this blog addresses many of the questions we hear on these topics.

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Producing Snake Venom— in the Lab

Posted on by Johanna Lee

Snakebite is a serious public health issue in many tropical countries. Every year, roughly 2 million cases of poisoning from snakebites occur, and more than 100,000 people die. Snake venom is extremely complex, containing a cocktail of chemicals, many of which are undefined. This complicates the development of new therapeutics for treating snakebite.

Antivenom is the most effective treatment for snakebites, but its production is complex and dangerous. It involves manually milking the venom from different species of live snakes, then injecting small doses of the venom into animals (mostly horses) to stimulate an immune response. After a period of time, antibodies form in the animal’s blood, which is purified for use as antivenom.

But what if we could produce snake venom in the lab, instead of using live snakes? Recently, a group from the Netherlands did just that by growing organoids derived from snake venom glands.

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The Race to Develop New Therapeutics Against Coronaviruses

Posted on by Michele Arduengo

Once the purview of virology researchers, the word “coronavirus” is now part of the vernacular in the mainstream media as reports of quarantined cruise ships (1) and makeshift hospitals (2) fill our online news feeds. While there is currently no approved anti-viral treatment for coronavirus infection (3), a team led by researchers from Vanderbilt University recently published work characterizing the anti-CoV activity of a compound, which they now plan to test against 2019-nCoV (4).

Developing New Therapeutics Against Coronaviruses

Coronaviruses (CoVs) are enveloped, single-stranded RNA viruses that exhibit cross-species transmission—the ability to spread quickly from one host (e.g., civet) to another (e.g., human). Scientists classify CoVs into four groups based on the nature of the spikes on their surface: alpha (α), beta (ß), gamma (γ) and delta (δ, 1). Only the alpha- and beta-CoVs can infect humans. Four coronaviruses commonly circulate within human populations: Human CoV 229E (HCoV229E), HCoVNL63, HCoVOC43, and HCoVHKU1. Three other CoVs have emerged as infectious agents, jumping from their normal animal host species to humans: SARS-CoV, MERS-CoV and most recently, 2019-nCoV (5).

TE micrograph of a single MERS-CoV
Digitally colorized transmission electron micrograph reveals ultrastructural details of a single Middle East respiratory syndrome coronavirus (MERS-CoV) virion. Image credit: National Institute of Allergy and Infectious Diseases

The need for an effective, broad spectrum treatment against HCoVs, has been brought into sharp focus by the recent outbreak of the 2019 Novel Coronavirus (2019-nCoV; 6).

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Popular Papers from Promega Authors

Posted on by Michele Arduengo

Promega is a chemistry and instrument supplier to scientists in diverse industries and research labs around the world. True. But we are more than just a supply company; we are scientists dedicated to supporting the work of other scientists. We want the science behind the technologies we develop to be both vetted and valued by the scientific community at large, which is one reason our scientists take the time to prepare and submit manuscripts to peer-reviewed journals. Here we call out some of our published research papers that were highly read in 2019. In the journal ACS Chemical Biology alone, five Promega-authored papers were among the top 10 most read papers in 2019. Here’s a quick review of the highlights from these ACS papers.

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Go with Your Gut: Understanding How the Microbiome and Diet Influence Health

Posted on by Mariel Mohns
microbiome_mouse_model

Over the past decade, microbiome research has provided key insights into the relationship between our gut and our health. There are trillions of organisms in our gut, comprising the microbiome that complements our human biology, distinct from our genome. These gut microbes affect us in many ways, from affecting our mental health to our ability to fight cancer.

At the University of Wisconsin-Madison, Federico Rey and his research group are trying to understand how our diet might help or harm the important microbial communities in our gut. “If we can understand how microbes interact with diet, we can personalize nutrition to match diet with the composition of the gut microbiome and promote health,” Rey says.

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Out-FOXOing High-Stage Neuroblastoma

Posted on by Natalie Larsen
Fluorescence microscopy of neuroblastoma cells.

In recent years, scientists have been hot on the trail of transcription factor FOXO3, tracing its involvement in various tumor-centric activities comprising the many trademarks of cancer, from drug resistance to metastasis to tumor angiogenesis.

FOXO3 is a member of the O sub-class of the forkhead box family of transcription factors. The forkhead box (FOX) family is characterized by a fork head DNA-binding domain (DBD), comprised of around 100 amino acids. They have also proven themselves to be a family of many hats, functioning in diverse roles ranging from metabolism, immunology, cell-cycle control, development, as well as cancer (1). The forkhead box O (FOXO) sub-class alone has demonstrated involvement in a variety of cellular outcomes, from drug resistance and longevity to apoptosis induction.

Due to its pro-apoptotic and anti-proliferative proclivity, FOXO3 has been previously identified as a tumor suppressor gene. However, more and more studies have begun to flip the narrative on FOXO3, portraying it more as a devoted henchman, due to its roles in drug and radiotherapy resistance, cell-cycle arrest and long-term maintenance of leukemia-initiating stem cells in a variety of cancer types, including breast cancer, pancreatic cancer, glioblastoma, and both acute and chronic myeloid leukemia.

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