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.
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.
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.
Clinical trials are arguably the backbone of medical advancement. But the trials most worth doing are usually large, costly and time-intensive, demanding extensive resources and personnel. During the COVID-19 pandemic, there has been a marked uptick in the number of clinical trials, many of which are woefully flawed with issues ranging from insufficient sample size to bad design. The published research that follows is often redundant or inconclusive.
So how can scientists designing and running clinical trials streamline their efforts to reduce waste and achieve more useful outcomes? The answer could be adaptive clinical trials.
Wearing blue surgical gowns and white respirator hoods, research scientist Pradeep Uchil and post-doctoral fellow Irfan Ullah carry an anesthetized mouse to the lab’s imaging unit. Two days ago, the mouse was infected with a SARS-CoV-2 virus engineered to produce a bioluminescent protein. After an injection of a bioluminescence substrate, a blue glow starts to emanate from within the mouse’s nasal cavity and chest, visible to the imaging unit’s camera and Uchil’s eyes.
“We were never able to see this kind of signal with retrovirus infections.” Uchil is a research scientist at the Yale School of Medicine whose work focuses on the in vivo imaging of retroviral infections. Normally, the mouse would have to be sacrificed and “opened up” for viral bioluminescent signals from internal tissues to be imaged directly.
Most of us, after we flush the toilet, don’t think twice about our body waste. To us, it’s garbage. To epidemiologists, however, wastewater can provide valuable information about public health and help save lives.
History of Wastewater-Based Epidemiology
Wastewater-based epidemiology (WBE) is the analysis of wastewater to monitor public health. The term first emerged in 2001, when a study proposed the idea of analyzing wastewater in sewage-treatment facilities to determine the collective usage of illegal drugs within a community. At the time, this idea to bridge environmental and social sciences seemed radical, but there were clear advantages. Monitoring wastewater is a nonintrusive and relatively inexpensive way to obtain real-time data that accurately reflects community-wide drug usage while ensuring the anonymity of individuals.
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.
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.
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.
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.
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