Researchers develop new method to synthesize cannabis plant compound

Photo Credit: Matthew Brodeur

A group of researchers at Leipzig University has developed a new method for synthesizing cis-tetrahydrocannabinol (THC) – a natural substance found in the cannabis plant that produces the characteristic psychoactive effect and has many potential applications, including in the pharmaceutical industry. “Our strategy makes it possible to produce cis-tetrahydrocannabinoids and test them for their biological activity,” explains researcher Caroline Dorsch, who, together with Professor Christoph Schneider from the Institute of Organic Chemistry, has published her findings in the journal Angewandte Chemie.

She points out that until now there has been no way of synthesizing this structural class in a consistent way. With their simple, inexpensive and nature-based synthesis, the Leipzig researchers have for the first time made the substance class of cis-tetrahydrocannabinoids accessible for a broad range of applications. The researcher notes that because previous methods required many steps and large amounts of chemicals and solvents, their approach is clearly superior. The substance can be synthesized with high overall yields and excellent optical purities using the new method.  

Deficiency causes appetite for meat

A carnivorous leaf of Triphyophyllum peltatum with glands excreting a sticky liquid to capture insect prey.
Photo Credit: Traud Winkelmann / Universität Hannover

Under certain circumstances, a rare tropical plant develops into a carnivore. A research team from the universities of Hannover and Würzburg has now deciphered the mechanism responsible for this.

Triphyophyllum peltatum is a unique plant. Native to the tropics of West Africa, the liana species is of great interest for medical and pharmaceutical research due to its constituents: In the laboratory, this show promising medically useful activities against pancreatic cancer and leukemia cells, among others, as well as against the pathogens that cause malaria and other diseases.

However, the plant species is also interesting from a botanical perspective: Triphyophyllum peltatum is the only known plant in the world that can become a carnivore under certain circumstances. Its menu then includes small insects, which it captures with the help of adhesive traps in the form of secretion drops and digests with synthesized lytic enzymes.

Putting the STING into cancer immunotherapy

Belcher and Hammond Lab researchers developed a cancer vaccine that could make checkpoint blockade therapies more effective for more patients.
Illustration Credit: Bendta Schroeder

Immune checkpoint blockade therapies have been revolutionary in the treatment of some cancer types, emerging as one of the most promising treatments for diseases such as melanoma, colon cancer, and non-small cell lung cancer.  

While in some cases checkpoint blockade therapies elicit a strong immune response that clears tumors, checkpoint inhibitors do not work for all tumor types or all patients. Moreover, some patients who do experience an initial benefit from these therapies see their cancers recur. Only a small minority of patients treated with checkpoint blockade therapies see lasting benefits. Researchers have developed various combination therapy strategies to overcome resistance to checkpoint blockade therapies, with the STING pathway emerging as one of the most attractive lines of inquiry.  

In a study appearing in Advanced Healthcare Materials, a team of MIT researchers engineered a therapeutic cancer vaccine capable of restoring STING signaling and eliminating the majority of tumors in mouse models of colon cancer and melanoma, with minimal side effects. The vaccine also inhibited metastasis in a breast cancer mouse model and prevented the recurrence of tumors in cured mice. 

Fecal beads to act at the core of the intestinal microbiota

Alginate microparticles containing isolated bacterial strains (white particles) and a fecal transplant (brown particles), with a zoom on the structure of the microparticles by scanning electron microscopy.
 Image Credits: © Adèle Rakotonirina et Nathalie Boulens
(CC BY-NC-ND 4.0)

A UNIGE team, in collaboration with the CHUV, has developed a new method of encapsulating fecal bacteria to treat a serious intestinal infection.

Clostridioides difficile infection causes severe diarrhea and results in the death of nearly 20,000 patients in Europe each year. It is one of the most common hospital-acquired infections. When it relapses, the disease must be treated by fecal microbiota transplantation. This treatment, which is administered via a nasogastric or colorectal tube, is very demanding. Researchers at the University of Geneva (UNIGE), in collaboration with the Lausanne University Hospital (CHUV), have developed small beads to be taken orally, which could radically improve its administration. This work can be found in the International Journal of Pharmaceutics.

Naturally found in 15% of the population, Clostridioides difficile is a bacterium that can become pathogenic when the protective "barriers" of our intestinal flora are weakened. This is particularly the case after prolonged and repeated use of antibiotics. Clostridioides difficile then causes severe diarrhea and can lead to a critical inflammation of the colon, known as pseudomembranous colitis. With more than 124,000 cases per year in Europe, it is one of the most common hospital-acquired infections and is fatal in about 15% of cases.

Efficient synthesis of indole derivatives, an important component of most drugs, allows the development of new drug candidates

Efficient synthesis of indole derivatives, an important component of most drugs,  allows the development of new drug candidates. 
Illustration Credit: Reiko Matsushita

A research group at Nagoya University in Japan has successfully developed an ultrafast and simple synthetic method for producing indole derivatives. Their findings are expected to make drug production more efficient and increase the range of potential indole-based pharmaceuticals to treat a variety of diseases. Their findings were published in Communications Chemistry. 

An indole is an organic compound consisting of a benzene ring and a pyrrole ring. Heteroatom alkylation at the carbon atom next to the indole ring is particularly useful to create a wide range of new indole derivatives and many anti-inflammatory, anticancer, and antimicrobial treatments contain them.

In the past, this heteroatom alkylation has proven difficult because indoles easily and rapidly undergo unwanted dimerization/multimerization, processes in which two or more molecules combine during the reaction to form unwanted larger molecules. These unwanted by-products limit the yield of the desired product.  

Scientists Identify Antivirals that Could Combat Emerging Infectious Diseases

Aedes aegypti mosquito.
Photo Credit: Pixabay

A new study has identified potential broad-spectrum antiviral agents that can target multiple families of RNA viruses that continue to pose a significant threat for future pandemics. The study, led by Gustavo Garcia Jr. in the UCLA Department of Molecular and Medical Pharmacology, tested a library of innate immune agonists that work by targeting pathogen recognition receptors, and found several agents that showed promise, including one that exhibited potent antiviral activity against members of RNA viral families.

The ongoing SARS-CoV-2 pandemic, which has claimed nearly seven million lives globally since it began, has revealed the vulnerabilities of human society to a large-scale outbreak from emerging pathogens. While accurately predicting what will trigger the next pandemic, the authors say recent epidemics as well as global climate change and the continuously evolving nature of the RNA genome indicate that arboviruses, viruses spread by arthropods such as mosquitoes, are prime candidates. These include such as Chikungunya virus (CHIKV), Dengue virus, West Nile virus and Zika virus. The researchers write: “Given their already-demonstrated epidemic potential, finding effective broad-spectrum treatments against these viruses is of the utmost importance as they become potential agents for pandemics.”

In their new study, published in Cell Reports Medicine, researchers found that several antivirals inhibited these arboviruses to varying degrees. “The most potent and broad-spectrum antiviral agents identified in the study were cyclic dinucleotide (CDN) STING agonists, which also hold promise in triggering an immune defense against cancer,” said senior author Vaithi Arumugaswami, Associate Professor in the UCLA Department of Molecular and Medical Pharmacology and a member of the California NanoSystems Institute.

Drug for rare form of ALS approved by FDA

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS). Called tofersen, the drug — developed by Biogen Inc. and based in part on research conducted at Washington University School of Medicine in St. Louis — slows the progression of the deadly, paralyzing disease. 

Video Credit: Huy Mach and Tamara Bhandari

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS), a paralyzing neurological disease. Known as tofersen, the drug has been shown to slow progression of the deadly disease. International clinical trials of tofersen, developed by the global biotechnology company Biogen Inc., were led by a neurologist at Washington University School of Medicine in St. Louis.

Tofersen, also known by the brand name Qalsody, is designed for ALS patients whose disease is caused by mutations in the gene SOD1. In the phase 3 clinical trial, the drug reduced molecular signs of disease and curbed neurodegeneration in the first six months of use. Over longer time frames, some participants experienced a stabilization of muscle strength and control.

The drug is approved under the accelerated approval pathway, under which FDA may approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

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.”

Revealed: Molecular “superpower” of antibiotic-resistant bacteria

Scanning electron micrograph of en:Clostridioides difficile bacteria from a stool sample
Photo Credit: Public Health Image Library

A species of ordinary gut bacteria that we all carry flourishes when the intestinal flora is knocked out by a course of antibiotics. Since the bacteria is naturally resistant to many antibiotics, it causes problems, particularly in healthcare settings. A study led from Lund University in Sweden now shows how two molecular mechanisms can work together make the bacterium extra resistant. “Using this knowledge, we hope to be able to design even better medicines,” says Vasili Hauryliuk, senior lecturer at Lund University, who led the study.

The threat from antibiotic resistant bacteria is as well-known as it is grave. Last year, The Lancet reported that an estimated 1.27 million people died in 2019 as a result of bacterial infection that could not be treated with existing medicines. To tackle this threat is it is essential to understand the underpinning molecular mechanisms.

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.

Drug form of traditional Chinese medicine compound improved survival of mice with brain tumors

Indirubin is a natural product present in indigo plants and the active ingredient of the traditional Chinese medicine Dang Gui Long Hui Wan, which is used to treat chronic diseases.
Photo Credit: Courtesy of Brown University

A new study shows how a drug made from a natural compound used in traditional Chinese medicine works against malignant brain tumors in mice, creating a promising avenue of research for glioblastoma treatment.

In the study, published in Cell Reports Medicine, researchers showed how a formulation of the compound, called indirubin, improved the survival of mice with malignant brain tumors. They also tested a new formulation that was easier to administer, taking the potential pharmaceutical approach one step closer to clinical trials with human participants.  

“The interesting thing about this drug is that it targets a number of important hallmarks of the disease,” said Sean Lawler, lead author, associate professor of pathology and laboratory medicine, and researcher at the Legorreta Cancer Center of Brown University. “That's appealing because this type of cancer keeps finding ways around individual mechanisms of attack. So, if we use multiple mechanisms of attack at once, perhaps that will be more successful.”

Modified Botox gives long-term pain relief after nerve injury without side effects

A single injection of the elongated Botox could relieve pain for months without risk of paralysis or addiction
Photo Credit: Mufid Majnun

A modified form of Botox could give long-term pain relief to patients with chronic nerve injury pain, according to a new study.

A team of scientists from the Universities of Sheffield, Reading and University College London (UCL) and US-based biopharmaceutical company Neuresta have created a new, elongated botulinum neurotoxin which can alleviate chronic pain without risk of paralysis or addiction. 

Chronic pain is extremely difficult to manage, and currently available drugs are limited by dangerous side effects. Opioids like morphine and fentanyl are the gold standard for short-term pain relief but they cannot effectively treat chronic pain due to the risk of addition, abuse and overdose. 

Findings of the new study, published in the journal Life Science Alliance, show that a single injection of the precisely engineered botulinum neurotoxin provides long-lasting relief in mice models, without adverse effects.

The team, led by Professor Bazbek Davletov, Chair of Biomedical Science, and Research Associate Charlotte Leese from the University of Sheffield, developed a new way of rebuilding Botox by using elements of Clostridium botulinum and created a biopharmaceutical with new properties, without unwanted toxic effects. 

Scientists Get Closer to Curing Alzheimer's and Parkinson's Diseases

In Russia, the incidence of dementia, Parkinson's disease and Alzheimer's disease will reach the epidemiological threshold of 5%
Image Credit: Gerd Altmann

Prospective compounds for the treatment of neurodegenerative diseases have been synthesized by Russian scientists. The compounds are of great interest for medicinal chemistry, especially for the development of treatments for Alzheimer's and Parkinson's diseases.

According to Timofey Moseev, a member of the group and an employee of the UrFU Chemical Pharmaceutical Center, the researchers managed to test the toxicity of the compounds in vitro on the kidney cells of a healthy human embryo. The researchers used the strategy of nucleophilic hydrogen substitution (a substitution reaction in which the substrate is attacked by a nucleophile, a reagent that carries a pair of unshared electrons). The process does not require metal catalysis, which is particularly important in the production of biologically active compounds, where any metal impurity can significantly distort toxicity and activity data.

To assess the ability of the synthesized molecules to bind to biotargets (proteins that play an important role in a particular disease), the researchers conducted experiments using docking - a molecular modeling technique. Docking allows predicting with a certain probability how a molecule interacts with targeted proteins.

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.

Understanding nitrogen metabolism could revolutionize TB treatment, finds study

Illustration Credit: Courtesy of University of Surrey

Development of new drugs to effectively target the bacterium that causes tuberculosis (TB) could be one step closer following an important discovery from the University of Surrey.

The Surrey study used a technology called fluxomics to reveal important information about how cells process nitrogen, which could help us better understand how harmful bacteria survive and cause disease. These findings have significant implications for studying the behavior and impact of pathogenic bacteria on human health.

In the most comprehensive study of its kind, the research team from Surrey conducted a study on the bacterium that causes tuberculosis, called Mycobacterium tuberculosis (Mtb). They wanted to understand how nitrogen is processed within Mtb cells, which is essential for the bacterium's survival. Surprisingly, previous studies had mostly examined the role of carbon in Mtb's survival, leaving the role of nitrogen poorly understood.

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.

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. 

Revolutionary new bone cancer drug could save children's lives

Osteosarcoma, Bone Cancer Cell
Cancer that starts in the bones, rather than cancer that has spread to the bone, predominantly affects children and young adults
Image Credit: National Cancer Institute

A new drug that works against the main types of primary bone cancer has been developed by researchers at the University of East Anglia and University of Sheffield.

Cancer that starts in the bones, rather than cancer that has spread to bone, predominantly affects children and young adults.      

Current treatment is brutal, with outdated chemotherapy cocktails and limb amputation leading to life-long disabilities.

Even after these grueling treatments, the five-year survival rate is still poor at just 42 per cent – largely because of how rapidly bone cancer spreads to the lungs. These rates haven’t changed in nearly half a century.

But a new study published in the Journal of Bone Oncology shows how a new drug called ‘CADD522’ blocks a gene associated with driving the cancer’s spread, in mice implanted with human bone cancer.

Lipid analysis of alcohol-related liver disease offers potential new therapeutic targets

Illustration Credit: youngseok park

Analyses of lipids identified differences between normal liver samples and liver samples from patients with alcohol-related liver disease. The information could be used to find new treatments and for earlier detection of the disease.

Alcohol-related liver disease (ALDs) is prevalent, with one in five people that misuse alcohol found to have exhibited liver fibrosis – damaged and scarred liver tissue and a marker of advanced ALDs such as cirrhosis. Alcohol is a leading cause of cirrhosis with half of worldwide deaths from cirrhosis being caused by alcohol.

ALD is characterized by severe liver damage that causes swelling, weight loss, drowsiness and vomiting blood. The number of people with ALD in the UK has risen in the last few decades as alcohol misuse has increased.

It is widely understood that excessive alcohol consumption affects liver function and the transport of lipids. But researchers and clinicians currently don’t understand the molecular development of alcohol-related liver diseases, particularly its early development.