Discovery identifies those likely to experience life-threatening dengue fever

(L-R) Co-first author and PhD student Stephanie Studniberg with senior researcher, Monash BDI’s Professor Diana Hansen.
Photo Credit: WEHI

Scientists have discovered cell populations in blood which clearly indicate whether a person infected with dengue fever is likely to progress to life-threatening severe disease or not.

About half of the world’s population is at risk of dengue fever, with almost 400 million annual cases. More will be at risk as global warming enables the spread of mosquito strains that carry the virus.

Until now, there has been no accurate way to predict which patients will progress to severe dengue fever. The new finding uses immune cells to grade potential severity, paving the way for improved patient management, health system savings, and the development of a biomarker test.

Published in the Journal of Biomedical Science, the international research team, led by Professor Diana Hansen at the Monash Biomedicine Discovery Institute, included WEHI in Melbourne, and Dr Tedjo Sasmono at the Eijkman Centre in Jakarta, Indonesia.

Durable, low-cost COVID-19 vaccine could help fill in gaps around the world

A protein-based COVID-19 vaccine developed by researchers at Stanford Medicine and their colleagues may be ideal for infants.
Image Credit: Gerd Altmann

In a study led by Stanford Medicine researchers, a low-cost COVID-19 vaccine that does not require refrigeration provided immunity in rhesus monkeys for one year.

A low-cost, protein-based COVID-19 vaccine tested in rhesus monkeys by Stanford Medicine researchers and colleagues offered immunity against known variants for at least one year. Researchers hope the vaccine, which can remain unrefrigerated for up to two weeks and may be especially beneficial for infants, will help alleviate the need for boosters while improving herd immunity around the world.

If the vaccine succeeds in human trials, it could be an alternative to the mRNA vaccines widely used for COVID-19, without drawbacks such as high expense and low-temperature storage requirements. Protein-based vaccines, which use protein fragments of the target virus rather than the whole virus, have been used for decades to protect against diseases such as shingles and hepatitis.

“Our motivation was to come up with a vaccine that would provide worldwide access to vaccination,” said Peter Kim, PhD, the Virginia and D.K. Ludwig Professor in Biochemistry. “In the case of the mRNA vaccines, for example, they are expensive, difficult to make and require storage in freezers. So, we wanted to solve those problems with this vaccine.”

Protein domain common to plants and animals plays role in COVID-19 infection

ORNL scientists mutated amino acids in a receptor protein, shown in green, which diminished interaction with the SARS-CoV-2 virus spike protein, shown in red. Mutating the receptor protein hampered the virus’s ability to infect host cells.
Image Credit: ORNL, U.S. Dept. of Energy

Oak Ridge National Laboratory scientists exploring bioenergy plant genetics have made a surprising discovery: a protein domain that could lead to new COVID-19 treatments.

Researchers found the same plasminogen-apple-nematode, or PAN, domain studied by ORNL in plants like poplar and willow is also present in the human NRP1 receptor protein. NRP1 is less studied than the ACE-2 receptor targeted by current COVID-19 treatments, but this research shows its promise as a future therapeutic target.

By mutating amino acids called cysteine residues in the PAN domain of NRP1, researchers disrupted the ability of the SARS-CoV-2 virus to use its spike protein to invade cells, as described in iScience. ORNL scientists have also linked PAN to the growth of cancerous tumors.

Lab-made antibodies offer potential cure for yellow fever

Captured through a microscope, this enlarged image illustrates how yellow fever virus (purple coloring) is below detectable levels in the blood of research animals given a monoclonal antibody after being exposed to the virus (bottom squares). By comparison, yellow fever virus is clearly visible in the blood of research animals that didn’t receive a monoclonal antibody (top squares). This research suggests lab-made antibodies may be able to cure people who get sick with yellow fever, a disease for which there is no approved treatment.
Image Credit: Oregon Health & Science University

New research from Oregon Health & Science University and collaborators indicates lab-made antibodies may be able to cure people infected with yellow fever, a virus for which there is no treatment.

The natural immune response to invading pathogens normally involves making protective proteins called antibodies. A study published in Science Translational Medicine suggests that a single monoclonal antibody infusion can strengthen the body’s fight against yellow fever.

In the study, the yellow fever virus was undetectable in all animals that received monoclonal antibody infusions after being exposed to the virus.

“Two monoclonal antibodies that we evaluated completely removed all signs of infection from research animals,” said the study’s corresponding author, Ben Burwitz, Ph.D., associate professor at OHSU’s Vaccine and Gene Therapy Institute and affiliate associate professor at OHSU’s Oregon National Primate Research Center.

ORNL-led team designs molecule to disrupt SARS-CoV-2 infection

Oak Ridge National Laboratory led a team of scientists to design a molecule that disrupts the infection mechanism of the SARS-CoV-2 coronavirus and could be used to develop new treatments for COVID-19 and future virus outbreaks.
Video Credit: Michelle Lehman/ORNL, U.S. Dept. of Energy

A team of scientists led by the Department of Energy’s Oak Ridge National Laboratory designed a molecule that disrupts the infection mechanism of the SARS-CoV-2 coronavirus and could be used to develop new treatments for COVID-19 and other viral diseases.

The molecule targets a lesser-studied enzyme in COVID-19 research, PLpro, that helps the coronavirus multiply and hampers the host body’s immune response. The molecule, called a covalent inhibitor, is effective as an antiviral treatment because it forms a strong chemical bond with its intended protein target.

“We’re attacking the virus from a different front, which is a good strategy in infectious disease research,” said Jerry Parks, who led the project and leads the Molecular Biophysics group at ORNL.

The research, detailed in Nature Communications, turned a previously identified noncovalent inhibitor of PLpro into a covalent one with higher potency, Parks said. Using mammalian cells, the team showed that the inhibitor molecule limits replication of the original SARS-CoV-2 virus strain as well as the Delta and Omicron variants.

Coronavirus causes chaos in infected cells’ RNA

Illustration Credit: Fusion Medical Animation

Coronavirus disease (COVID-19) hijacks parts of infected cells' vital RNA machinery, thereby blocking important functions in the cells. These damaging changes in the RNA can likely be reversed, potentially leading to new drugs against COVID-19, University of Gothenburg researchers show.

Genetic material in the body's cells consists of DNA, which serves as long-term storage of genetic information. RNA carries this encoded information to the cells for transcription and translation. These processes enable them to make proteins, which perform most intracellular tasks. The cells' RNA is modifiable to allow correct transfer of the DNA information to the proteins. In recent years, scientific understanding of the complexity and importance of these RNA modifications has grown.

Drastic impact

It has been shown that RNA modifications take place in various viruses, but exactly how the viruses affect the RNA modification processes when they infect cells is unknown. This study reports that SARS-CoV-2 infection disrupts the RNA modifications, and the extent of these RNA modification changes surprised the researchers.

One of the modifications affected by SARS-CoV-2, known as m6A (a multifaceted regulator of gene expression), is highly important for RNA’s basic functions, including transportation of data to the protein-making parts of the cell, and transcription and translation into amino acids there.

“We were surprised at the extent and drastic scale of m6A RNA modification loss in SARS-CoV-2 infection. We also found that the coronavirus variants have differing effects on m6A levels,” says Tanmoy Mondal, researcher at Sahlgrenska Academy, University of Gothenburg, who led the project.

HIV can persist for years in myeloid cells of people on antiretroviral therapy

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

NIH-funded study confirms white blood cell subtype as HIV reservoir, suggests new target for cure efforts.

A subset of white blood cells, known as myeloid cells, can harbor HIV in people who have been virally suppressed for years on antiretroviral therapy, according to findings from a small study supported by the National Institutes of Health. In the study, researchers used a new quantitative method to show that HIV in specific myeloid cells—short-lived monocytes and longer-lived monocyte-derived macrophages—can be reactivated and infect new cells. The findings, published in Nature Microbiology, suggest that myeloid cells contribute to a long-lived HIV reservoir, making these cells an important but overlooked target in efforts to eradicate HIV.

“Our findings challenge the prevailing narrative that monocytes are too short-lived to be important in cure efforts,” said study author Rebecca Veenhuis, Ph.D., an assistant professor of molecular and comparative pathobiology and of neurology at Johns Hopkins University School of Medicine, Baltimore. “Yes, the cells are short-lived, but our follow-up data show that HIV can persist in monocytes over several years in people who are virally suppressed. The fact that we can detect HIV in these cells over such a long period suggests something is keeping the myeloid reservoir going.”

Wastewater could be the key to tracking more viruses than just COVID-19

Boehm lab graduate student Winnie Zambrana showing how wastewater samples are processed to test for evidence of viruses.
Photo Credit: Harry Gregory

Researchers have developed methods for using wastewater to track the levels of various respiratory viruses in a population. This can provide real-time information about virus circulation in a community.

Public health experts commonly track spikes in flu, respiratory syncytial virus (RSV), and rhinovirus circulating in a population through weekly reports from sentinel laboratories. These laboratories process samples from only severely ill patients, and it can take weeks for the results to get into the database. Now, for the first time, researchers at Stanford University, in collaboration with Emory University and Verily Life Sciences, have collected fast and accurate readings of a whole suite of respiratory viruses in their local Santa Clara sewer system.

Wastewater is currently the only source for accurate information about COVID-19 rates in communities. PCR testing is no longer widely available, and most people swab themselves at home where their results never reach public health agencies.

Prior to COVID-19, respiratory viruses had not been tracked through wastewater. Most of the viruses the scientists tested for in this study had never been measured in wastewater before. The findings are published in the March 22 issue of The Lancet Microbe.

Researchers develop a universal oral COVID-19 vaccine that prevents severe illness in hamsters

Illustration Credit: PIRO

A UCLA-led team has developed an inexpensive, universal oral COVID-19 vaccine that prevented severe respiratory illness and weight loss when tested in hamsters, which are naturally susceptible to SARS-CoV-2. It proved as effective as vaccines administered by injection or intranasally in the research.

If ultimately approved for human use, it could be a weapon against all COVID-19 variants and boost uptake, particularly in low- and middle-income countries, and among those with an aversion to needles.

The study is published in the peer-reviewed journal Microbiology Spectrum.

The oral vaccine is based primarily on the nucleocapsid protein, which is the most abundantly expressed of the virus’s four major structural proteins and evolves at a much slower rate than the frequently mutating spike protein. The vaccine utilizes a highly weakened bacterium to produce the nucleocapsid protein in infected cells as well as the membrane protein, which is another highly abundant viral structural protein.

Lack of canine COVID-19 data fuels persisting concerns over dog-human interactions

A research literature review by Purdue University researchers published in the journal Animals highlights unanswered questions about the COVID-19 virus dynamics between dogs and humans.
 Photo Credit: Purdue Agricultural Communications photo/Tom Campbell

Early COVID-19 pandemic suspicions about dogs’ resistance to the disease have given way to a long-haul clinical data gap as new variants of the virus have emerged.

“It is not confirmed that the virus can be transmitted from one dog to another dog or from dogs to humans,” said veterinarian Mohamed Kamel, a postdoctoral fellow at Purdue University.

During the pandemic’s early days, dogs seemed resistant to the coronavirus, showing little evidence of infection or transmission, said Mohit Verma, assistant professor of agricultural and biological engineering and Purdue’s Weldon School of Biomedical Engineering. “As the virus evolved, or maybe the surveillance technology advanced, there seem to be more instances of potentially asymptomatic dogs.”

These are among the findings that Kamel, Verma and two co-authors summarized in a research literature review “Interactions Between Humans and Dogs in the COVID-19 Pandemic.” The summary, with recent updates and future perspectives, recently appeared in a special issue of the journal Animals on Susceptibility of Animals to SARS-CoV-2.

Underactive immune response may explain obesity link to COVID-19 severity

Intensive care unit at Addenbrooke's Hospital 
Photo Credit: Cambridge University Hospitals NHS Foundation Trust

Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.

Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with almost 6.9 million deaths. While some people have very mild – or even no – symptoms, others have much more severe symptoms, including acute respiratory distress syndrome requiring ventilator support.

One of the major risk factors for severe COVID-19 is obesity, which is defined as a body mass index (BMI) of over 30. More than 40% of US adults and 28% of adults in England are classed as obese.

While this link has been shown in numerous epidemiological studies, until now, it has not been clear why obesity should increase an individual’s risk of severe COVID-19. One possible explanation was thought to be that obesity is linked to inflammation: studies have shown that people who are obese already have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain the connection?

Known active ingredient as new drug candidate against “monkeypox”

Mpox Virus
Image Credit: Samuel F. Johanns

Mpox – previously known as "monkeypox" – is currently spreading worldwide. An international research team from Goethe University and the University of Kent has now identified a compound that could help fight the disease. Their study has been published in the “Journal of Medical Virology". 

Nitroxoline is the name of the new drug candidate that could potentially be used to treat mpox. It was identified by scientists at Goethe University and the University of Kent as part of a multi-site study. The results of their research will now allow clinical trials to begin soon. 

The current mpox outbreak is the first of this size to occur outside of Africa and also the first mpox outbreak caused by human-to-human transmission. People with immunodeficiencies are particularly at risk from the disease. Although antiviral agents have already been shown to inhibit the replication of the mpox virus in experimental models, the efficacy of these substances has not yet been confirmed in humans and some may have significant side effects. In addition, there are insufficient stocks to treat all mpox patients. Moreover, resistance formation against tecovirimat, the most promising mpox drug candidate to date, has already been reported. 

Bird Flu Associated with Hundreds of Seal Deaths in New England in 2022

A seal may contract the virus if it comes in contact with a sick bird’s excrement or water contaminated by that excrement. Seals and sea birds have environmental contact, if not direct contact, since they share the same water and shoreline.
Photo Credit: Lucía Montenegro

Researchers at Cummings School of Veterinary Medicine at Tufts University found that an outbreak of highly pathogenic avian influenza (HPAI) was associated with the deaths of more than 330 New England harbor and gray seals along the North Atlantic coast in June and July 2022, and the outbreak was connected to a wave of avian influenza in birds in the region.

The study was published on March 15 in the journal Emerging Infectious Disease.

HPAI is more commonly known as bird flu, and the H5N1 strain has been responsible for about 60 million poultry deaths in the U.S. since October 2020, with similar numbers in Europe. The virus was known to have spilled over from birds into mammals, such as minks, foxes, skunks, and bears, but those were mostly small, localized events. This study is among the first to directly connect HPAI to a larger scale mortality event in wild mammals.

The co-first authors on the paper—virologist and senior scientist Wendy Puryear and post-doctoral researcher Kaitlin Sawatzki, who both work in the Runstadler Lab at Cummings School—have been researching viruses in seals for years. They credit their findings in the new study to a unique and robust data set made possible by a collaboration with wildlife clinics and rehabilitation and response organizations in the region, in particular with Tufts Wildlife Clinic and director Maureen Murray, V03, associate clinical professor at Cummings School, and an author on the paper.

Designing More Useful Bacteria

An illustration of viruses called phages infecting a bacterial cell.
Illustration Credit: Behnoush Hajian

In a step forward for genetic engineering and synthetic biology, researchers have modified a strain of Escherichia coli bacteria to be immune to natural viral infections while also minimizing the potential for the bacteria or their modified genes to escape into the wild.

The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels. Currently, viruses that infect vats of bacteria can halt production, compromise drug safety, and cost millions of dollars.

“We believe we have developed the first technology to design an organism that can’t be infected by any known virus,” said the study’s first author, Akos Nyerges, research fellow in genetics in the lab of George Church in the Blavatnik Institute at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering.

“We can’t say it’s fully virus-resistant, but so far, based on extensive laboratory experiments and computational analysis, we haven’t found a virus that can break it,” Nyerges said.

The work also provides the first built-in safety measure that prevents modified genetic material from being incorporated into natural cells, he said.

Research team proves bacteria-killing viruses deploy genetic code-switching to deceive hosts

ORNL scientists proved the theory that bacteria-destroying viruses called bacteriophages use genetic code-switching to first infect and later overwhelm their hosts.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

Scientists at the Department of Energy’s Oak Ridge National Laboratory have confirmed that bacteria-killing viruses called bacteriophages deploy a sneaky tactic when targeting their hosts: They use a standard genetic code when invading bacteria, then switch to an alternate code at later stages of infection.

Their study provides crucial information on the life cycle of phages. It could be a key step toward the development of new technologies such as therapeutics targeting human pathogens or methods to control phage-bacterial interactions in applications ranging from plant production to carbon sequestration.

Scientists have predicted since the mid-1990s that some organisms may use an alternate genetic code, but the process had never been observed experimentally in phages. ORNL researchers obtained the first experimental validation of this theory using uncultivated phages in human fecal samples and the lab’s high-performance mass spectrometry to reveal the intricacies of how phage proteins are expressed in the host organism. The work is detailed in Nature Communications.

COVID-19 infections raise risk of long-term gastrointestinal problems

Ziyad Al-Aly, MD, has led multiple studies on long COVID-19 as a clinical epidemiologist at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care system. His latest findings show that people who have been infected with COVID-19 are at an increased risk of developing a range of gastrointestinal conditions within the first month to a year after illness.
Photo Credit: Matt MIller / School of Medicine / Washington University in St. Louis

People who have had COVID-19 are at increased risk of developing gastrointestinal (GI) disorders within a year after infection compared with people who haven’t been infected, according to an analysis of federal health data by researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care system.

Such conditions include liver problems, acute pancreatitis, irritable bowel syndrome, acid reflux and ulcers in the lining of the stomach or upper intestine. The post-COVID-19 GI tract also is associated with an increased likelihood of constipation, diarrhea, abdominal pain, bloating and vomiting.

“Gastrointestinal problems were among the first that were reported by the patient community,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University who has studied extensively the long-term effects of COVID-19 infection. “It is increasingly clear that the GI tract serves as a reservoir for the virus.”

Study finds silicon, gold and copper among new weapons against COVID-19

New Curtin research has found the spike proteins of SARS-CoV-2, a strain of coronaviruses that caused the COVID-19 pandemic, become trapped when they come into contact with silicon, gold and copper, and that electric fields can be used to destroy the spike proteins, likely killing the virus.

Lead researcher Dr Nadim Darwish, from the School of Molecular and Life Sciences at Curtin University said the study found the spike proteins of coronaviruses attached and became stuck to certain types of surfaces.

“Coronaviruses have spike proteins on their periphery that allow them to penetrate host cells and cause infection and we have found these proteins becomes stuck to the surface of silicon, gold and copper through a reaction that forms a strong chemical bond,” Dr Darwish said.

“We believe these materials can be used to capture coronaviruses by being used in air filters, as a coating for benches, tables and walls or in the fabric of wipe cloths and face masks.

Could a Naturally Occurring Amino Acid Lead Us to a Cure for COVID-19?

An amino acid called 5-aminolevulinic acid (ALA) might be key to reduce the expression of ACE2, a cell membrane receptor that SARS-CoV-2 uses to infect cells. New insights gained by scientists at Tokyo Tech have clarified the relationship between ACE2, ALA, and the production of heme, which could pave the way to anti-viral drugs to cure COVID-19.

After more than two years since its discovery, six million deaths, and half a billion reported cases, there is still no effective cure for COVID-19. Even though vaccines have lowered the impact of outbreaks, patients that contract the disease can only receive supportive care while they wait for their own body to clear the infection.

A promising COVID-19 treatment strategy that has been gaining traction lately is targeting angiotensin-converting enzyme 2 (ACE2). This is a receptor found on the cell membrane that allows entry of the virus into the cell due to its high affinity for SARS-CoV-2’s spike protein. The idea is that reducing the levels of ACE2 on the membrane of cells could be a way to prevent the virus from entering them and replicating, thereby lowering its infectious capabilities.

Using sewage to forecast COVID-19 infections

Collecting samples at a wastewater treatment plant for the study
Photo Credit: provided by Masaaki Kitajima

Sifting through sewage for SARS-CoV-2 genetic material could help authorities tailor infection control policies.

A new mathematical model uses wastewater samples to effectively forecast the number of clinical COVID-19 cases in a community five days in advance. The approach was developed and validated by Hokkaido University environmental engineer, Masaaki Kitajima, and colleagues in Japan. It could help healthcare authorities better tailor infection control policies, especially when clinical surveillance is lacking. The researchers reported their findings in the journal Environment International. 

Testing wastewater samples for SARS-CoV-2 as a means to predict surges in clinical cases has been attracting attention. Scientists have been researching this approach since the beginning of the pandemic. However, current methods aren’t particularly sensitive and can only detect increasing cases without being able to forecast their numbers within a community.

Kitajima and his colleagues had already developed a method to detect SARS-CoV-2 RNA in wastewater samples. But this method requires solid material and does not work well with diluted wastewater on rainy days or with treated wastewater that has been clarified and is mostly liquid. So, they modified their approach. Instead of using low-speed centrifugation to create pellets from wastewater samples that then go on to be tested, they used special filters that can capture the viral RNA from diluted wastewater. This is followed by extracting RNA from the filter, amplifying it, and then running polymerase chain reaction (PCR) tests to detect it. They call the new method Efficient and Practical Virus Identification System with Enhanced Sensitivity for Membrane (EPISENS-M).

NIH RECOVER research identifies potential long COVID disparities

Colorized scanning electron micrograph of a cell (purple) infected with the Omicron strain of SARS-CoV-2 virus particles (teal), isolated from a patient sample.
Image Credit: NIAID

NIH-supported studies show variations in symptoms and diagnostic experiences among different racial and ethnic groups.

Black and Hispanic Americans appear to experience more symptoms and health problems related to long COVID, a lay term that captures an array of symptoms and health problems, than white people, but are not as likely to be diagnosed with the condition, according to new research funded by the National Institutes of Health. The findings – from two different studies by NIH’s Researching COVID to Enhance Recover (RECOVER) Initiative – add to a growing body of research aimed to better understand the complex symptoms and other issues associated with long COVID that millions have experienced.

“This new evidence suggests that there may be important differences in how long COVID manifests in different racial and ethnic groups,” said Mitchell S.V. Elkind, M.D., a professor of neurology and epidemiology at Columbia University, New York City, and chief clinical science officer for the American Heart Association. “However, further research is needed to better understand the mechanisms for these differences in symptoms and access to care, and also if diagnostic codes assigned by clinicians may play a role.”