The 2019 Novel Coronavirus (SARS-CoV-2) is a new virus that emerged in China in late 2019 and quickly jumped into scientific and mainstream news. When facing a potential pandemic, it can be difficult to share information without inducing panic. There’s no doubt that SARS-CoV-2 presents a significant threat to public health, but as with all viruses in their emerging stages, we often find ourselves with more questions than answers. However, through the work of the World Health Organization (WHO), government officials and hardworking scientists worldwide, we can begin to understand some of the details about SARS-CoV-2.
The three winners of the 2019 Real-Time PCR Grants have been hard at work in the six months since receiving their grants. Each winner was eligible to receive up to $10,000 in free PCR reagents as well as the opportunity to collaborate with our knowledgeable technical service and training teams.
Abbeah Navasca is a plant pathology researcher with the Tagum Agricultural Development Company, Inc. (TADECO*, Philippines). She is developing treatments for viral infections that affect one of Philippines’ largest and most valuable agricultural exports: bananas. As a result of the qPCR grant, she and two of her colleagues were able to participate in sample preparation and analysis workshops with Promega Technical Services experts in Singapore. During her visit, the team worked through strategies for plant sample preparation and amplified those samples with the GoTaq® 1-Step RT-qPCR System. We had a chance to ask her more before she headed back to her lab.
Later this year, Promega will open a new R&D building with more than twice the current amount of lab space available on the Madison campus. While preparing to move to the new building, R&D scientists are cleaning out decades of scientific history housed in some of the older labs. Meagan Eggers, Promega Strategic Information Partner, is collaborating with the research groups to document and preserve noteworthy artifacts unearthed in the Research & Development Center. Over the next few months, we’ll showcase some of the most interesting things we find.
Spectrometer – 1960s-2000
Promega research scientists began investigating bioluminescent proteins in the early 1990s. One of the most important tools in this research was the spectrometer pictured above, which was used to measure the emission spectra of many different organisms. Before it arrived at Promega, however, this spectrometer began in the space program.
Remdesivir (RDV or GS-5734) was used in the treatment of the first case of the SARS-CoV-2 (formerly 2019-nCoV ) in the United States (1). RDV is not an approved drug in any country but has been requested by a number of agencies worldwide to help combat the SARS-CoV-2 virus (2). RDV is an adenine nucleotide monophosphate analog demonstrated to inhibit Ebola virus replication (3). RDV is bioactivated to the triphosphate form within cells and acts as an alternative substrate for the replication-necessary RNA dependent RNA polymerase (RdRp). Incorporation of the analog results in early termination of the primer extension product resulting in the inhibition.
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Photo Credit: Alissa Eckert, MS; Dan Higgins, MAM CDC
Why all the interest in RDV as a treatment for SARS-CoV-2 ? Much of the interest in RDV is due to a series of studies performed by collaborating groups at the University of North Carolina Chapel Hill (Ralph S. Baric’s lab) and Vanderbilit University Medical Center (Mark R. Denison’s lab) in collaboration with Gilead Sciences.
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.
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).
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).
It’s the time of year in the northern US when you start to
the miss green grass, ample daylight and warm breezes that are still months
away. The promise of spring’s renewal and seedlings sprouting from the
snow-covered ground seems too far out to even indulge in a daydream of better
weather.
But then again, I’m not a farmer.
The Promega Culinary Garden at Bluebird Farms.
Now is the time of year when farmers are reflecting on last
year’s harvest, making decisions about changes that need to be made and
planning for the upcoming growing season. This work includes choosing what
plants and varieties will be planted, estimating how many of each are needed
and ordering the seeds. Crop rotation and cover crops are also part of the
considerations.
If you’re a regular reader of this blog, you may know that Promega has a culinary garden that supplies some of the produce for our cafeterias on the Madison campus. During the growing season our Culinary Gardener, Logan Morrow, oversees the operations of Bluebird Farms with the help of his colleage Mike Daugherty.
Our cells have evolved multiple mechanisms for “taking out
the trash”—breaking down and disposing of cellular components that are defective,
damaged or no longer required. Within a cell, these processes are balanced by
the synthesis of new components, so that DNA, RNA and proteins are constantly
undergoing turnover.
Proteins are degraded by two major components of the cellular
machinery. The discovery of the lysosome in the mid-1950s
provided considerable insight into the first of these degradation mechanisms
for extracellular and cytosolic proteins. Over the next several decades,
details of a second protein degradation mechanism emerged: the ubiquitin-proteasome system
(UPS). Ubiquitin is a small, highly conserved polypeptide that is used to
selectively tag proteins for degradation within the cell. Multiple ubiquitin
tags are generally attached to a single targeted protein. This ill-fated, ubiquitinated
protein is then recognized by the proteasome, a large protein complex with
proteolytic activity. Ubiquitination is a multistep process, involving several
specialized enzymes. The final step in the process is mediated by a family of ubiquitin
ligases, known as E3.
In times of rapid growth, we look to the future with excitement while also assuring that our expansion is sustainable. The Promega Global Facilities Planning Team emphasizes environmental stewardship and long-term planning. Each building is designed to meet ambitious sustainability goals, and innovations incorporated into each project inform the next. In 2019, we finished construction on two new buildings in Europe and made progress on two important facilities at our headquarters in Wisconsin.
As Promega grows globally and locally here at headquarters, the construction of new and expanding facilities are considered with great care to ensure a commitment to sustainability. Between April and November of 2019, the parking ramp located near the Feynman Center received a massive upgrade with long-term impacts on the company’s sustainability goals.
