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.” 

Canine distemper now threatens big cats in Nepal

 A Bengal tiger in the jungle. Although researchers have suspected distemper was infecting tigers and leopards, a new study is the first definitive proof of infection in Nepal’s big cats.
Photo Credit: R. Gilbert

Researchers with the College of Veterinary Medicine have confirmed the first cases of canine distemper virus (CDV), which can cause fatal neurological disease, in tigers and leopards in Nepal.

“Canine distemper virus has been repeatedly identified as a threat to wild carnivores and their conservation,” said Martin Gilbert, Cornell Wildlife Health Center wild carnivore health specialist and associate professor of practice in the Department of Population Medicine and Diagnostic Sciences. “This study is a first step to understanding the potential impact for Nepalese tiger and leopard populations.”

Although researchers have suspected distemper was infecting these species, the study, published Jan 28 in the journal Pathogens, is the first definitive proof of infection in Nepal’s big cats. The survey found 11% of tigers (three out of 28) and 30% of the leopards (six out of 20) had antibodies to CDV, indicating prior infection with the virus.

Relatively little is known about the status of Nepal’s leopards, but scientists believe the population is in decline due to a combination of poaching, habitat loss and human-wildlife conflict. Leopards also face increasing competition for space due to the expansion of the country’s tiger population. Could CDV push them even further into decline?

Extracts from two wild plants inhibit COVID-19 virus

 Emory University graduate student Caitlin Risener, first author of the study, gathers tall goldenrod in South Georgia.
Photo Credit: Tharanga Samarakoon

Two common wild plants contain extracts that inhibit the ability of the virus that causes COVID-19 to infect living cells, an Emory University study finds. Scientific Reports published the results — the first major screening of botanical extracts to search for potency against the SARS-CoV-2 virus.

In laboratory dish tests, extracts from the flowers of tall goldenrod (Solidago altissima) and the rhizomes of the eagle fern (Pteridium aquilinum) each blocked SARS-CoV-2 from entering human cells.

The active compounds are only present in miniscule quantities in the plants. It would be ineffective, and potentially dangerous, for people to attempt to treat themselves with them, the researchers stress. In fact, the eagle fern is known to be toxic, they warn.

“It’s very early in the process, but we’re working to identify, isolate and scale up the molecules from the extracts that showed activity against the virus,” says Cassandra Quave, senior author of the study and associate professor in Emory School of Medicine’s Department of Dermatology and the Center for the Study of Human Health. “Once we have isolated the active ingredients, we plan to further test for their safety and for their long-range potential as medicines against COVID-19.”

Single drug injection wards off COVID-19 hospitalizations

A single injection of PEG-lambda interferon proved to be effective against all variants of the coronavirus tested by researchers at Stanford Medicine.
Image Credit: Gerd Altmann

In an international, multicenter, pivotal Phase 3 trial, a single under-the-skin injection of a biological drug given to patients within seven days of the onset of COVID-19 symptoms cut the likelihood they needed to be hospitalized in half. Patients treated within three days of showing symptoms fared even better. Among unvaccinated patients who were treated soon after symptom onset, hospitalization likelihood plummeted markedly.

The drug, pegylated lambda-interferon, or PEG-lambda, proved effective against all COVID-19 viral variants tested, including omicron. Side effects were no greater than those reported by placebo recipients.

A report on the success of the randomized, double-blind, placebo-controlled trial of nearly 2,000 newly infected COVID-19 patients was published online Feb. 9 in the New England Journal of Medicine.

PEG-lambda is a synthetic version of lambda-interferon, a naturally occurring protein that infected cells secrete as a first line of defense against viral infection.

Inhalable ‘SHIELD’ Protects Lungs Against COVID-19, Flu Viruses

Photo Credit: Robina Weermeijer

Researchers have developed an inhalable powder that could protect lungs and airways from viral invasion by reinforcing the body’s own mucosal layer. The powder, called Spherical Hydrogel Inhalation for Enhanced Lung Defense, or SHIELD, reduced infection in both mouse and non-human primate models over a 24-hour period, and can be taken repeatedly without affecting normal lung function.

“The idea behind this work is simple – viruses have to penetrate the mucus in order to reach and infect the cells, so we’ve created an inhalable bioadhesive that combines with your own mucus to prevent viruses from getting to your lung cells,” says Ke Cheng, corresponding author of the paper describing the work. “Mucus is the body’s natural hydrogel barrier; we are just enhancing that barrier.”

Cheng is the Randall B. Terry, Jr. Distinguished Professor in Regenerative Medicine at North Carolina State University’s College of Veterinary Medicine and a professor in the NC State/UNC-Chapel Hill Joint Department of Biomedical Engineering.

The inhalable powder microparticles are composed of gelatin and poly(acrylic acid) grafted with a non-toxic ester. When introduced to a moist environment – such as the respiratory tract and lungs – the microparticles swell and adhere to the mucosal layer, increasing the “stickiness” of the mucus.

How hepatitis E viruses penetrate cells

It was only around three years ago that a cell culture model was developed that can be used to examine hepatitis E exactly in the laboratory.
Photo Credit: RUB, Marquar

A certain surface protein is important for the cell entry of the hepatitis E virus. Medicines can suppress it.

Although hepatitis E is a common disease, little is known about the life cycle of the virus. A team from Molecular and Medical Virology at the Ruhr University Bochum and Carl von Ossietzky University Oldenburg reports on initial findings on how he manages to infect cells in the journal Hepatology from 7. February 2023. A protein called EGFR, short for Epidermal Growth Factor Receptor, plays a decisive role in the penetration of virus particles into cells. This finding could open up new treatment routes for hepatitis E. Because there are already approved drugs against EGFR that inhibit the activity of this receptor.

Cell culture model makes investigations possible

One of the reasons why hepatitis E has been researched comparatively little is that it was only around three years ago in Bochum and Hanover a robust cell culture model has been developed for its investigation is. Using this model, the researchers were now able to investigate how the virus manages to infect cells.

"With medication, we suppressed the activity of the EGFR protein at the time the virus entered some cell lines," explains first author Jil Alexandra Schrader. “With these cultures, we could see that there were significantly fewer infected cells." The researchers used cell cultures as a cross-check, in which the co-receptor was produced in excess. In this case, there were more infections than untreated cells.

Deer carry SARS-CoV-2 variants that are extinct in humans

White-tailed deer
Photo Credit: Heidi-Ann Fourkiller | SFLORG

White-tailed deer ­– the most abundant large mammal in North America – are harboring SARS-CoV-2 variants that once widely circulated but are no longer found in humans.

Whether or not deer could act as long-term reservoirs for these variants that have become obsolete in people is unknown, as scientists need more time and study to verify if it’s true.

The study, “White-tailed Deer (Odocoileus virginianus) May Serve as a Wildlife Reservoir for Nearly Extinct SARS-CoV-2 Variants of Concern,” which published Jan. 31 in the journal Proceedings of the National Academy of Sciences, represents one of the most comprehensive studies to date to assess the prevalence, genetic diversity and evolution of SARS-CoV-2 in white-tailed deer. The study focused on the white-tailed deer population in New York.

“One of the most striking findings of this study was the detection of co-circulation of three variants of concern – alpha, gamma and delta – in this wild animal population,” said Dr. Diego Diel, associate professor in the Department of Population Medicine and Diagnostic Sciences and director of the Virology Laboratory at the College of Veterinary Medicine’s (CVM) Animal Health Diagnostic Center. 

Over the course of the pandemic, deer have become infected with SARS-CoV-2 through ongoing contact with humans, possibly from hunting, wildlife rehabilitations, feeding of wild animals or through wastewater or water sources, though no one knows for sure.

Scientists Document Two Separate Reservoirs of Latent HIV in Patients

Rebound DNA sequences from the blood (red) and the CSF (blue)
Illustration Credit: Ron Swanstrom | UNC Center for AIDS Research | Swanstrom lab

This research, led by UNC School of Medicine scientists Laura Kincer, Sarah Joseph, PhD, and Ron Swanstrom, PhD, with international collaborators, shows that in addition to HIV’s ability to lay dormant in the blood/lymphoid system, the virus may also lay dormant in the central nervous system, delineating another challenge in creating a cure.

When people living with HIV take antiviral therapy (ART), their viral loads are driven so low that a standard blood test cannot detect the virus. However, once ART is stopped, detectable HIV re-emerges with new cells getting infected. This is called “rebound” virus, and the cells that release the virus to re-ignite the infection come from a small population of HIV-infected CD4+ T cells that had remained dormant in blood and lymph tissue while individuals were on ART.

It’s a problem called latency, and overcoming it remains a major goal for researchers trying to create curative therapies for HIV—the special focus of the UNC HIV Cure Center.

Marburg vaccine shows promising results in first-in-human study

Colorized scanning electron micrograph of Marburg virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (orange).
Image Credit: National Institute of Allergy and Infectious Diseases

A newly published paper in The Lancet shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small, first-in-human clinical trial. The vaccine, developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, could someday be an important tool to respond to Marburg virus outbreaks.

This first-in-human, Phase 1 study tested an experimental MARV vaccine candidate, known as cAd3-Marburg, which was developed at NIAID’s Vaccine Research Center (VRC). This vaccine uses a modified chimpanzee adenovirus called cAd3, which can no longer replicate or infect cells, and displays a glycoprotein found on the surface of MARV to induce immune responses against the virus. The cAd3 vaccine platform demonstrated a good safety profile in prior clinical trials when used in investigational Ebola virus and Sudan virus vaccines developed by the VRC.

New virus discovered in whales, dolphins across the Pacific

Photo Credit: Richard Sagredo

A novel virus, potentially fatal to whales and dolphins, has been discovered by researchers at the University of Hawaiʻi Health and Stranding Lab. Prior to its discovery in 10 whale and dolphin host species across the Pacific, the virus was found in only a single marine mammal worldwide, a Longman’s beaked whale stranded on Maui in 2010. The findings were published in Frontiers in Marine Science.

The discovery of beaked whale circovirus (BWCV) in whales and dolphins expands the knowledge of marine mammal species that can become infected with the disease. Circoviruses are DNA viruses that cause disease in birds, pigs and dogs, and in severe cases can become fatal.

“Our study found Cuvier’s beaked whales tested positive for BWCV in Saipan and American Samoa, nearly 4,000 miles away from the first discovered case,” said Kristi West, director of the UH Health and Stranding Lab. “The positive cases found outside of Hawaiʻi were surprising, and indicates that this virus is spread across the Central and Western Pacific and may have a global presence in marine mammals.”

Highly accurate test for common respiratory viruses uses DNA as ‘bait’

Doctor examining a patient
Photo Credit: Thirdman

The test uses DNA ‘nanobait’ to detect the most common respiratory viruses – including influenza, rhinovirus, RSV and COVID-19 – at the same time. In comparison, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. The results are reported in the journal Nature Nanotechnology.

The winter cold, flu and RSV season has arrived in the northern hemisphere, and healthcare workers must make quick decisions about treatment when patients show up in their hospital or clinic.

Mucosal antibodies in the airways provide durable protection against SARS-CoV-2

Charlotte Thålin, M.D. and associate professor at the Department of Clinical Sciences, Danderyd Hospital
Photo Credit: Ludvig Kostyal

Researchers hope that a nasal vaccine may generate mucosal immune responses that protect against SARS-CoV-2 infection.

High levels of mucosal IgA antibodies in the airways protect against SARS-CoV-2 infection for at least eight months. Omicron infection generates durable mucosal antibodies, reducing the risk of re-infection. These are the findings of a study published in The Lancet Infectious Diseases by researchers at Karolinska Institutet and Danderyd Hospital in Sweden. The results raise further hope for the feasibility of future nasal vaccine platforms to protect against infection.

“Antibodies in the blood protect from severe disease, but if we aim to limit infection, viral transmission and the emergence of new SARS-CoV-2 variants, we need to reinforce our immunity at the mucosal surface, which is the viral point of entry”, says Charlotte Thålin, M.D. and associate professor at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet who led the study. “This is not achieved by currently employed intramuscularly-delivered vaccines. But the hope is that a nasal vaccine may generate mucosal immune responses similar to those seen after infection, and thereby block the transmission chain”.