Discovery of how COVID-19 virus replicates opens door to new antiviral therapies

A new study, looking at the replication stage of the SARS-CoV-2 virus that causes COVID-19, discovered important mechanisms in its replication that could be the foundation for new antiviral therapies.
Image Credit: Gerd Altmann

The study, which sets out to investigate how the SARS-CoV-2 virus replicates once it enters the cells, has made surprising discoveries that could be the foundation for future antiviral therapies. It also has important theoretical implications as the replication of the SARS-CoV-2 virus has, so far, received less attention from researchers.

The viral life cycle can be broken down into two main stages: the first stage is where the virus enters the cell. The second stage is replication where the virus uses the molecular machinery of the cell it has infected to replicate itself by building its parts, assembling them into new viruses that can then exit to infect other cells.

The majority of research into SARS-CoV-2 – the causative agent of COVID-19 – has focused on the Spike protein that allows viral entry. This has led to a lack of understanding of how the virus replicates once it has entered the cell.

A new paper led by Dr Jeremy Carlton in collaboration with Dr David Bauer at the Francis Crick Institute, focuses on how the Envelope protein of SARS-CoV-2 controls late stages of viral replication.

Discovery could end global amphibian pandemic

Panamanian golden frog
Photo Credit: Brian Gratwicke/U.S. Fish & Wildlife Service

A fungus devastating frogs and toads on nearly every continent may have an Achilles heel. Scientists have discovered a virus that infects the fungus, and that could be engineered to save the amphibians.

The fungus, Batrachochytrium dendrobatidis or Bd, ravages the skin of frogs and toads, and eventually causes heart failure. To date it has contributed to the decline of over 500 amphibian species, and 90 possible extinctions including yellow-legged mountain frogs in the Sierras and the Panamanian golden frog. 

A new paper in the journal Current Biology documents the discovery of a virus that infects Bd, and which could be engineered to control the fungal disease.

The UC Riverside researchers who found the virus are excited about the implications of their discovery. In addition to helping them learn about how fungal pathogens rise and spread, it offers the hope of ending what they call a global amphibian pandemic. 

“Frogs control bad insects, crop pests, and mosquitoes. If their populations all over the world collapse, it could be devastating,” said UCR microbiology doctoral student and paper author Mark Yacoub. 

“They’re also the canary in the coal mine of climate change. As temperatures get warmer, UV light gets stronger, and water quality gets worse, frogs respond to that. If they get wiped out, we lose an important environmental signal,” Yacoub said. 

New Method Developed to Isolate HIV Particles

The image shows PNF-coated magnetic microbeads that bind HIV particles to their surface.
Image Credit: Torsten John

Researchers at Leipzig University and Ulm University have developed a new method to isolate HIV from samples more easily, potentially making it easier to detect infection with the virus. They focus on peptide nanofibrils (PNFs) on magnetic microparticles, a promising tool and hybrid material for targeted binding and separation of viral particles. They have published their new findings in the journal Advanced Functional Materials.

“The presented method makes it possible to efficiently capture, isolate and concentrate virus particles, which may improve the sensitivity of existing diagnostic tools and analytical tests,” says Professor Bernd Abel of the Institute of Technical Chemistry at Leipzig University. The nanofibrils used – small, needle-like structures – are based on the EF-C peptide, which was first described in 2013 by Professor Jan Münch from Ulm University and Ulm University Medical Center. EF-C is a peptide consisting of twelve amino acids that forms nanoscale fibrils almost instantaneously when dissolved in polar solvents. These can also be applied to magnetic particles. “Using the EF-C peptide as an example, our work shows how peptide fibrils on magnetic particles can have a completely new functionality – the more or less selective binding of viruses. Originally, fibrils of this kind were more likely to be associated with neurodegenerative diseases,” adds Dr Torsten John, co-first author of the study and former doctoral researcher under Professor Abel at Leipzig University. He is now a junior researcher at the Max Planck Institute for Polymer Research in Mainz, Germany.

Researchers a step closer to a cure for HIV

HIV, the AIDS virus (yellow), infecting a human cell
Image Credit: National Cancer Institute

A new study involving University of Bristol researchers has shown a virus-like particle (HLP) can effectively 'shock and kill' the latent HIV reservoir.

By 2030, the World Health Organization (WHO), the Global Fund and UNAIDS are hoping to end the human immunodeficiency virus (HIV) and AIDS epidemic. An international team of researchers led by Professor Eric Arts from the Schulich School of Medicine & Dentistry, Canada, and Dr Jamie Mann, Senior Lecturer at the University of Bristol, has brought us another step closer to meeting this goal, by finding an effective and affordable targeted treatment strategy for an HIV cure. 

In a first, the study published in Emerging Microbes and Infections demonstrated the team's patented therapeutic candidate. The HIV-virus-like-particle (HLP), is 100 times more effective than other candidate HIV cure therapeutics for people living with chronic HIV on combined antiretroviral therapy (cART). If successful in clinical trials, HLP could be used by millions of people living around the world to free them of HIV. This study was done using blood samples from people living with chronic HIV. 

HLPs are dead HIV particles hosting a comprehensive set of HIV proteins that increase immune responses without infecting a person. When compared with other potential cure approaches, HLP is an affordable biotherapeutic and can be administered by intramuscular injection – similar to the seasonal flu vaccine. 

Research offers hope for preventing post-COVID ‘brain fog’ by targeting brain’s blood vessels

Blood vessel endothelial cells (green) and basement membrane (red) in the brain.
Image Credit: Sarah Lutz

Among the many confounding symptoms in patients recovering from a COVID-19 infection are memory loss and difficulty learning. Yet little is known about the mechanisms of cognitive impairments like these, commonly called brain fog. 

In a new study, researchers at the University of Illinois Chicago have identified a mechanism that causes neurological problems in mice infected with SARS-CoV-2, the virus behind COVID-19. The researchers also found a treatment that helped prevent these changes. Sarah Lutz, assistant professor of anatomy and cell biology in the College of Medicine, led the research, which was published in the journal Brain.

The team focused on the blood-brain barrier, which plays a role in other neurological diseases, such as multiple sclerosis. Normally, this barrier protects the brain from potentially harmful cells or molecules circulating in the bloodstream. But the infected mice, researchers found, had leaky blood-brain barrier vessels and impaired memory or learning.

To understand why, the researchers looked at blood vessels from the brains of infected mice to see which genes were most altered. They found a significant decrease in a signaling pathway called Wnt/beta-catenin, which helps maintain the health of the blood-brain barrier and protects the brain from damage.

Long COVID linked to persistently high levels of inflammatory protein: a potential biomarker and target for treatments

"We hope that this could help to pave the way to develop therapies and give some patients a firm diagnosis," -Benjamin Krishna
Photo Credit: Annie Spratt

SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle ache and depression. New research shows that in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for therapies.

A University of Cambridge-led study identifies the protein interferon gamma (IFN-γ) as a potential biomarker for Long COVID fatigue and highlights an immunological mechanism underlying the disease, which could pave the way for the development of much needed therapies, and provide a head start in the event of a future coronavirus pandemic. 

The study, published today in Science Advances, followed a group of patients with Long COVID fatigue for over 2.5 years, to understand why some recovered and others did not. 

Long COVID continues to affect millions of people globally and is placing a major burden on health services. An estimated 1.9 million people in the UK alone (2.9% of the population) were experiencing self-reported Long COVID as of March 2023, according to the ONS. Fatigue remains by far the most common and debilitating symptom and patients are still waiting for an effective treatment.

Targeting inflammation to tackle long covid

Illustration Credit: Gerd Altmann

Overactivation of the immune system leading to circulation of inflammatory proteins around the body contributes to the development of long covid, and could be targeted to provide treatments for patients, finds new research.

Cardiff University research has uncovered biological markers that could be targeted by repurposing medication to treat long covid.

The research conducted extensive analysis of plasma samples obtained from a large cohort of healthy post-covid individuals and non-hospitalized patients with long covid. They found that the complement system – a system that plays a crucial part of the immune system, consisting of a group of proteins that work together to enhance the function of antibodies and immune cells – was commonly overactivated in those with long covid.

“The covid-19 pandemic has left a global legacy of ill health, with long covid estimated to affect up to 1.9 million people in the UK. Long covid can last for months or years after the triggering infection and is associated with diverse symptoms including brain fog, chest pain, breathlessness, fatigue, and sensory problems. The causes of this disease remain largely unknown, emerging evidence suggests an important role for chronic inflammation."
Professor Paul Morgan 'Professor of complement biology, Division of Infection and Immunity

New COVID vaccine induces good antibody response to mutated viral variants

Photo Credit: CDC

Researchers at Karolinska Institutet and Danderyd Hospital have followed recipients of the new updated COVID-19 vaccine and analyzed the antibody response to different SARS-CoV-2 variants. The results show a surprisingly strong response to the now dominant and highly mutated Omicron variants.

The ongoing COMMUNITY study, which was launched in the spring of 2020 with the regular testing of 2,149 members of the Danderyd Hospital staff, has recently published the results of this autumn’s leg of the study. Twenty-four participants were recorded in this study, the majority of whom were over 64 and had received four or five previous vaccine doses. The article has been peer-reviewed and accepted for publication in the scientific journal The Lancet Infectious Diseases, and is accessible prior to publication on the preprint server, bioRxiv.

Deadly chicken disease: ancient DNA reveals evolution of virulence

With the increase in poultry farming, Marek's disease virus evolved
Photo Credit: Heidi-Ann Fourkiller

Using genetic analyses, an international team led by LMU paleogeneticist Laurent Frantz has revealed the evolutionary history of the pathogen of a fatal disease in chickens.

A notifiable animal disease in Germany, Marek’s disease is caused by the globally distributed Marek’s disease virus (MDV). Over the past century, the virus, which causes tumors in chickens and has a high mortality rate, has become increasingly aggressive. Combating the disease costs the poultry industry over a billion dollars every year. With the help of ancient DNA, an international team of scientists led by LMU paleogenomicist Professor Laurent Frantz and Professor Greger Larson and Professor Adrian Smith from the University of Oxford has now decoded the evolution of MDV and shed light on what is behind the growing virulence.

The international team from the fields of paleogenetics, archeology, and biology isolated viral genomes from chicken bones up to 1,000 years old from 140 archeological sites in Europe and the Near East. “Our data shows that the virus was already widely distributed at least 1,000 years before the first description of the disease in 1907,” says Frantz. When the disease was first described, it was said to produce only mild symptoms in older chickens. With the dramatic increase in poultry farming in the 1950s and 1960s, the virus evolved and has become increasingly virulent despite the development of several vaccines.

How the Immune System Fights to Keep Herpes at Bay

These microscope images show how interferon in the nucleus raises levels of the protective protein IFI16 (stained green) from low background levels (left) to the higher levels needed to resist herpes infection (right).
Image Credit: HMS MicRoN core imaging facility/Nicolas Romero Rata

Herpes simplex virus (HSV) is extremely common, affecting nearly two-thirds of the world’s population, according to the World Health Organization.

Once inside the body, HSV establishes a latent infection that periodically awakens, causing painful blisters on the skin, typically around the nose and mouth. While a mere nuisance for most people, HSV can also lead to dangerous eye infections and brain inflammation in some people and cause life-threatening infections in newborns.

Researchers have long known that the virus and the host immune system are in a perpetual competition, but why does this battle reach a stasis in most people while causing serious infections in others?

More important, precisely how does the battle unfold at the level of cells and molecules? This question has continued to bedevil scientists and hamper the quest for treatments that prevent or cure infections.

A recent study by researchers at Harvard Medical School, conducted using lab-engineered cells and published in PNAS, unveils the precise maneuvers used by host and pathogen in the fight for dominance of the cell.

Temperature increase triggers viral infection

Illustration of phage virus injecting its DNA into a cell
Illustration Credit: Alex Evilevitch and Ting Liu

Researchers at Lund University, together with colleagues at the NIST Synchrotron Facility in the USA, have mapped on an atomic level what happens in a virus particle when the temperature is raised.

"When the temperature rises, the virus's genetic material changes its form and density, becoming more fluid-like, which leads to its rapid injection into the cell," says Alex Evilevitch who led the study.

Viruses lack their own metabolism and the ability to replicate independently; they are entirely dependent on a host cell to multiply. Instead, the virus hijacks the internal machinery of the infected cell to produce new virus particles, which are then released and spread to infect other cells.

In most cases, the virus's genetic material, DNA, is enclosed within a protective protein shell called a capsid. A research group at Lund University is working to understand the process by which the virus ejects its genetic material from the capsid and into cells and what causes the virus's DNA to be released.

It all began with a study published in 2014, where the Lund University researchers observed that there seems to be a sudden change in the virus's genetic material when exposed to the infection temperature, around 37 degrees.

Success of Wolbachia-infected mosquitoes in fighting dengue may be underestimated

Alex Perkins, associate professor of biological science
Photo Credit: Courtesy of University of Notre Dame

The fight against dengue fever has a new weapon: a mosquito infected with the bacteria Wolbachia, which prevents the spread of the virus. These mosquitoes have now been deployed in several trials demonstrating their potential in preventing disease transmission.

Now, researchers at the University of Notre Dame have conducted an analysis of the World Mosquito Program’s randomized control trial of Wolbachia-infected mosquitoes in Indonesia, looking at how excluding transmission dynamics impacted the original interpretation of the trial’s results.

“Randomized controlled trials are the gold standard for evaluating the efficacy of any medical or public health intervention. That is very difficult for vector interventions against dengue because incidence of the disease can be somewhat unpredictable and sporadic, requiring very large-scale trials,” said Alex Perkins, associate professor of biological sciences at Notre Dame and senior author on the study.

The Unraveling of a Protist Genome Could Unlock the Mystery of Marine Viruses

Light-microscopy image of clusters of Aurantiochytrium limacinum cells. The marine protist is prevalent in the world’s oceans.
Image Credits: Laura Halligan, Joshua Rest and Jackie Collier

Viruses are the most prevalent biological entities in the world’s oceans and play essential roles in its ecological and biogeochemical balance. Yet, they are the least understood elements of marine life. By unraveling the entire genome of a certain marine protist that may act as a host for many viruses, an international research team led by scientists from Stony Brook University sets the stage for future investigations of marine protist genomes, marine microbial dynamics and the evolutionary interplay between host organisms and their viruses — work that may open doors to a better understanding of the “invisible” world of marine viruses and offers a key to the ecology and health of oceans worldwide. The research is published early online in Current Biology.

Food webs of the oceans provide humanity with essential food sources as well as the wonderment of sea creatures from polar bears to penguins. This wellspring of life is supported mainly by microscopic organisms, including the wide presence of viruses. Learning more about the viruses through DNA research and other forms of investigation is essential to scientists’ understanding of the sea. Novel groups of viruses are still being discovered, such as the recently discovered “mirusvirues” featured in a Nature paper earlier this year.

Pinpointing HIV immune response

HIV, the AIDS virus (yellow), infecting a human cell
Image Credit: National Cancer Institute

New research combining computer modeling and experiments with macaques shows the body’s immune system helps control human immunodeficiency virus (HIV) infections largely by suppressing viral production in already infected cells while also killing viral infected cells, but only within a narrow time window at the start of a cell’s infection.

“To eliminate HIV, we have to understand how the immune system attempts to control the infection,” said Ruy M. Ribeiro, a theoretical biologist at Los Alamos National Laboratory who led the development of the model underpinning the research. Ribeiro is the corresponding author of the paper about the findings, published in Nature Communications.

The research team included Los Alamos Senior Fellow Alan S. Perelson and a former Los Alamos postdoctoral researcher now at the Fred Hutchinson Cancer Research Center. Their collaborators at the University of Pittsburg managed the experiments with macaques infected with simian immunodeficiency virus (SIV) to validate the model. SIV infections in monkeys behave the same way as HIV in humans.

Long COVID most prevalent in the most seriously ill

Image Credit: Scientific Frontline

A collaborative study involving researchers from Karolinska Institutet has charted the prevalence of severe physical symptom burden amongst Scandinavians for up to two years after a SARS-CoV-2 infection. Most affected were people who had a severe COVID-19 infection, while the researchers found no elevated prevalence of long COVID in those who had never been bedridden. The study is published in The Lancet Regional Health – Europe.

By mid-October 2023, over 771 million cases of COVID-19 had been reported to the World Health Organization (WHO). An estimated 10 to 20 per cent of the affected have persistent symptoms.

Close to 65,000 participants

In the present study, researchers examined the prevalence of persistent physical symptoms in people with different degrees of COVID-19 severity and compared them with people who had not had a confirmed COVID-19 diagnosis. The study comprised 64,880 adults from Sweden, Denmark, Norway and Iceland with self-reported physical symptoms between April 2020 and August 2022.

Over 22,000 of the participants were diagnosed with COVID-19 during the period, almost 10 per cent of whom were bedridden for at least seven days. The prevalence of chronic symptoms such as shortness of breath, chest pain, dizziness, headaches, and low energy/ fatigue, was 37 per cent higher in those who had had a COVID-19 diagnosis than in those who had not.

Zika Infection in Pregnant Macaques Slows Fetal Growth

Female rhesus macaque monkeys and infants at the California National Primate Research Center at UC Davis.
Photo Credit: Courtesy of University of California, Davis

Zika virus infection in pregnant rhesus macaques slows fetal growth and affects how infants and mothers interact in the first month of life, according to a new study from researchers at the California National Primate Research Center at the University of California, Davis. The work, published Oct. 25 in Science Translational Medicine, has implications for both humans exposed to Zika virus and for other viruses that can cross the placenta, including SARS-CoV2, responsible for the COVID-19 pandemic.

“Initially I thought this was a story about Zika, but as I looked at the results, I think this is also a story about how fetal infections in general affect developmental trajectories,” said Eliza Bliss-Moreau, professor of psychology at UC Davis and senior author on the paper.

In most people, Zika virus infection causes mild or no symptoms and leaves long-lasting immunity. But during pregnancy, the virus can cross the placenta and cause damage to the nervous system of the fetus. In extreme cases, it can cause microcephaly in humans.

Scientists uncover cause of mysterious deaths of elephants in Zimbabwe

Photo Credit: Charl Durand

During this unique study, scientists from the Victoria Falls Wildlife Trust, the Animal and Plant Health Agency UK, the University of Surrey and laboratories in South Africa investigated the mysterious deaths of 35 elephants mostly between August and September 2020, in a 40 x 25 km radius of North-Western Zimbabwe. This incident followed the death of approximately 350 elephants in neighboring northern Botswana from May to June 2020, which triggered much international concern. 

African savanna elephants are an endangered species with only 350,000 remaining in the wild and ongoing losses estimated at eight percent annually. This finding is very worrying since elephants are on the International Union for Conservation of Nature red list already. Investigating the deaths of these elephants is crucial to sustaining the future of this majestic species. 

Post-COVID condition is not linked to ongoing infection or active brain damage

Post COVID-19 condition does not appear to be linked to direct viral invasion of the brain or active brain damage. This has been shown by a study at the University of Gothenburg. Searching for abnormal biomarkers among the participants yielded no hits in either blood or cerebrospinal fluid samples.

The condition that can follow the acute phase of COVID-19 infection, termed “Post-COVID condition,” or “long-covid” can persist for several months subsequent to the initial infection. The condition includes various combinations of fatigue, apathy, and difficulties with memory and concentration.

The current study, published in The Journal of Infectious Diseases, included 25 people with confirmed post-COVID condition, six people without residual symptoms after COVID-19, and 17 control subjects who were completely free of COVID-19.

The strength of the study lies not in the number of participants, which is fairly limited, but in the fact that they all – including the control subjects – underwent not only blood tests but also the considerably more invasive procedure of lumbar punctures to collect cerebrospinal fluid.

At the time when the samples were taken, at least three months had passed since the first symptoms of COVID-19 in those who had had the disease. The samples were taken between February and November 2021, and were analyzed for a total of 37 different biomarkers.

Preventing Airborne Infection without Impeding Communication with Ions and Electric Field

Figure 1.
Novel device for preventing airborne infection The design (a) and schematic (b) of the mechanism of the device for capturing infectious droplets and aerosols without hindering communication. The negatively charged ions attach to the droplets and the electric field guides them to the collecting electrode.
Illustration Credit: Courtesy of Tokyo Institute of Technology

A novel device developed by Tokyo Tech researchers in a new study utilizes ions and an electric field to effectively capture infectious droplets and aerosols, while letting light and sound pass through to allow communication. The innovation is significant in the wake of the COVID-19 pandemic, since it shows promise in preventing airborne infection while facilitating communication.

Airborne infections, such as H1N1 influenza, SARS, and COVID-19, are spread by aerosols and airborne droplets. While droplet/aerosol transmission can be prevented using acrylic partitions or, as with the COVID-19 pandemic, by imposing lockdowns in severe cases, these countermeasures can significantly impede communication. This, in turn, can lead to unintended consequences.

For instance, lockdown measures during the COVID-19 pandemic led to severe economic losses as well as a rise in cases of mental illness like depression and suicide around the world. Therefore, as we prepare for a potential future pandemic, it is necessary to develop more sustainable countermeasures that do not disrupt economic activities and daily face-to-face interactions.

To this end, a research team including Kaito Kanda, a graduate student at Tokyo Institute of Technology (Tokyo Tech) at the time of research, Assistant Professor Tetsuya Yamada, from the Institute of Innovative Research at Tokyo Tech, and Professor Takeo Fujiwara from Tokyo Medical and Dental University (TMDU) and Chiba University researchers, has now developed a device that successfully captures droplets and aerosols while allowing the transmission of light and sound for effective communication.

Boosting weak immune system: scientists find an unusual weapon against virus

An overview of how the method proposed by the Sieweke group boosts weak immune system. (A) M-CSF cytokine works in the bone marrow to promote generation of monocytes and macrophages, without disturbing the formation of other immune cells; (B) Monocytes and macrophages activate natural killer cells to enable them to target virus-infected cells and kill them through cell–cell contact and the release of toxic agents.
Illustration Credit: © EMBO
(CC BY 4.0 DEED)

Infections with cytomegalovirus (CMV) are extremely common and often pose no major threat to the vast majority of people. They can, however, be deadly for people whose immune system is weakened, e.g., after bone marrow transplantation. Current treatments against CMV infections are very limited and can have severe side effects. Researchers led by Prof. Michael Sieweke at the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology and the Center of Immunology of Marseille Luminy (CIML) propose a new way to protect against CMV. Instead of targeting the virus, their approach boosts the weak immune system and lets it fight the virus on its own. The results were published in the journal EMBO Molecular Medicine.

Some viruses can be dormant throughout a person’s life and cause no harm but become dangerous when the immune system is weakened. One such virus is human cytomegalovirus (CMV). Harmless to the general public but life-threatening to patients with a suppressed immune system.