COVID-19 Antiviral Therapies: What Are the New Drugs, and How Do They Work?

We’re entering the third year of the global COVID-19 pandemic, and it’s far from over. There has been considerable progress with SARS-CoV-2 vaccine development, with most of the focus on mRNA vaccines and adenoviral vector vaccines. Meanwhile, novel vaccine delivery systems are being tested among efforts to develop a “pan-coronavirus” vaccine that is effective against multiple variants. One such example is ferritin nanoparticle technology developed by researchers at the Walter Reed Army Institute of Research and their collaborators. Encouraging results from nonhuman primate studies, using several SARS-CoV-2 antigens, were published in 2021 (1–3).

New COVID-19 antiviral therapies offer promise, but further data are needed before they become widely available.

The current surge in COVID-19 cases that began last month is largely due to the Omicron variant in the US, according to data from the US Centers for Disease Control and Prevention (CDC). At present, we still don’t know enough about this variant, but it’s clear that its rapid spread is forcing us to re-examine what we know about SARS-CoV-2 (4). As the virus continues to mutate, new variants will continue to emerge and spread. Although current vaccines can provide protection against multiple variants, breakthrough infections are a concern. Vaccination is still the best option to reduce the risk of infection, hospitalization, and death compared to unvaccinated people.

It’s clear that vaccines are only part of an effective response to fighting the pandemic. Along with continued vaccine development efforts, attention must also be given to antiviral drug development for people already infected with COVID-19. Due to the lengthy process for new drug development, early efforts focused on repurposing existing drugs.

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MISpheroID: A Knowledgebase to Improve Reproducibility in Spheroid Research

Spheroid research is  now a common component of cell biology and drug discovery science

Advantages of Spheroids

In the past decade, there has been a sharp rise in studies using spheroids as cell models for basic research and drug discovery. Spheroids are self-organized aggregation of cells that form a spherical mass, and they have become widely popular because they are much more physiologically relevant compared to flat 2D cell cultures.

In spheroids, the inner cells have less access to nutrients and oxygen compared to the outer layer, forming a natural gradient. As a result, metabolite concentration and cellular state such as proliferation and differentiation, can be very different at the periphery compared to the inner core. This phenomenon, known as “heterogeneity”, makes 3D tumor spheroids much more representative of actual tumors in the human body.

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Total Eclipse of the CAR T: How mRNA Vaccine Technology Can Be Used to Help Heal “Broken” Hearts

While you can rely on Taylor Swift and Adele to help heal emotional heartbreak, unfortunately treating a physically “broken” heart, a heart damaged by fibrosis, is a much more complicated process than putting on your favorite sad songs and wallowing in your feelings. In a recent study published in Science, researchers developed a therapeutic approach to treat damaged hearts in mice through the removal of scar tissue using genetically engineered immune cells (CAR T cells) and the mRNA technology used in the mRNA coronavirus vaccines.

Genetically engineered CAR T cells have been used l for repairing damaged hearts in mice
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Kicking Off the New Year with Three Popular Plant Papers

It’s officially 2022, Happy belated New Year! A lot of amazing research is trending in science news right now. In particular, take a look at three plant-related papers that discuss interesting research and advancements in plant science.

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Run to Remember: A Mouse-Model Study Investigating the Mechanism of Exercise-Induced Neuroprotection

Research in animal models shows physical exercise can induce changes in the brain. In humans, studies also revealed changes in brain physiology and function resulting from physical exercise, including increased hippocampal and cognitive performance (1). Several studies in mice and rats also demonstrated that exercise can improve learning and memory and decrease neuroinflammation in models of Alzheimer’s disease and other neurodegenerative pathologies (2); these benefits are tied to increased plasticity and decreased inflammation in the hippocampus in mice (2). If regular time pounding the pavement does improve brain function, what is the underlying molecular biology of exercise-induced neuroprotection? Can we identify the cellular pathways and components involved? Can we detect important components in blood plasma? And, is the benefit of these components transferrable between organisms? De Miguel and colleagues set out to answer these questions and describe their results in a recent study published in Nature.

A recent study investigates the underlying molecular mechanisms of exercise-induced neuroprotection in a mouse model.
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COVID-19 Intranasal Vaccines Revisited: Can They Reduce Breakthrough Infections?

COVID-19 cases are now being identified primarily among unvaccinated individuals, according to data from the US Centers for Disease Control and Prevention (CDC). However, there has been increasing concern about so-called breakthrough infections among fully vaccinated individuals, particularly after the emergence of the SARS-CoV-2 Delta variant.

COVID-19, sars-cov-2

What is a breakthrough infection? The CDC defines it as “the infection of a fully vaccinated person.” The key finding remains that people with breakthrough infections are still far less likely to experience severe COVID-19 symptoms, in contrast with unvaccinated people; hence the importance of vaccination.

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There’s a Microbiome In My Tank!

Imagine a scenario—you’re studying the developmental biology of a species of squid. The squid don’t reproduce in captivity, so females carrying fertilized eggs are collected from the wild and rehomed in your lab’s aquariums. You’ve monitored all the normal aquarium conditions—pH, temperature, salinity—ensuring the animal’s new home mimics its natural environment.

But then, for no reason apparent to you, the clutch of eggs doesn’t develop and doesn’t hatch, derailing your research program until next year when you can collect more adult squid from the wild. What went wrong?

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

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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How Can You Improve Protein Digests for Mass Spectrometry Analysis?

Can predigestion with trypisin (ribbon structure shown) improve protein digests for mass spectrometry analysis?
Can pre-digestion with trypsin improve mass spec analysis?

The trypsin protease cleaves proteins on the carboxyterminus of Arginine (Arg) and Lysine (Lys). This cleavage reaction leaves a positive charge on the C-terminus of the resulting peptide, which enhances mass spectrometry analysis (1,2). Because of this advantage, trypsin has become the most commonly used protease for mass spectrometry analysis. Other proteases which cleave diffrently from trypsin, yielding complementary data are also used in mass spec analysis: these include Asp-N and Glu-C , which cleave acidic residues, and chymotrypsin which cleaves at aromatic residues. The broad spectrum protease, proteinase K is also used for some proteomic analyses. In a recent study, Dau and colleagues investigated whether sequential digestion with trypsin followed by the complementary proteases could improve protein digests for mass spectrometry analysis.

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

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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