Researchers at Karolinska Institutet in Sweden have developed a novel strategy for identifying potent miniature antibodies, so-called nanobodies, against emerging SARS-CoV-2 variants. The approach led to the discovery of multiple nanobodies that in cell cultures and mice effectively blocked infection with different SARS-CoV-2 variants. The findings, which are described in the journals Nature Communications and Science Advances, could pave the way for new treatments against COVID-19.
Despite the roll-out of vaccines and antivirals, the need for effective therapeutics against severe COVID-19 infection remains high. Nanobodies—which are fragments of antibodies that occur naturally in camelids and can be adapted for humans—are promising therapeutic candidates as they offer several advantages over conventional antibodies. For example, they have favorable biochemical properties and are easy to produce cost-effectively at scale.
In the now published studies, the labs of Gerald McInerney and Ben Murrell, also at MTC, identify several potent nanobodies derived from an alpaca immunized with SARS-CoV-2 antigens.
The first report in Nature Communications describes a single nanobody, Fu2 (named after the alpaca Funny), that significantly reduced the viral load of SARS-CoV-2 in cell cultures and mice. Using electron cryo-microscopy, the researchers found that Fu2 naturally binds to two separate sites on the viral spike, thus inhibiting the virus’ ability to enter the host cell. This part of the study was conducted in collaboration with Hrishikesh Das and Martin Hällberg at the Department of Cell and Molecular Biology at Karolinska Institutet.
The researchers next delved deeper into the alpaca’s nanobody repertoire by combining a range of advanced laboratory techniques and computational methods, resulting in a library of nanobodies described in detail.
The results, presented in Science Advances, revealed additional nanobodies that in cell cultures and mice effectively cross-neutralized both the founder and beta variant of SARS-CoV-2 and even neutralized the more distantly related SARS-CoV-1.
“These nanobodies represent promising therapeutic candidates against several SARS-CoV-2 variants,” says first author Leo Hanke, a postdoctoral researcher who established the nanobody technology in the McInerney group.
The researchers are currently applying the same techniques to identify which nanobodies from this set are best able to neutralize omicron, the now dominating SARS-CoV-2 variant.
“Once established, these libraries can be expanded and mined for nanobodies that neutralize new emerging variants,” says Assistant Professor Ben Murrell, also joint senior author of both studies.
News
Ultrasound-activated Nanoparticles Kill Liver Cancer and Activate Immune System
A new ultrasound-guided nanotherapy wipes out liver tumors while training the immune system to keep them from coming back. The study, published in Nano Today, introduces a biodegradable nanoparticle system that combines sonodynamic therapy and cell [...]
Magnetic nanoparticles that successfully navigate complex blood vessels may be ready for clinical trials
Every year, 12 million people worldwide suffer a stroke; many die or are permanently impaired. Currently, drugs are administered to dissolve the thrombus that blocks the blood vessel. These drugs spread throughout the entire [...]
Reviving Exhausted T Cells Sparks Powerful Cancer Tumor Elimination
Scientists have discovered how tumors secretly drain the energy from T cells—the immune system’s main cancer fighters—and how blocking that process can bring them back to life. The team found that cancer cells use [...]
Very low LDL-cholesterol correlates to fewer heart problems after stroke
Brigham and Women's Hospital's TIMI Study Group reports that in patients with prior ischemic stroke, very low achieved LDL-cholesterol correlated with fewer major adverse cardiovascular events and fewer recurrent strokes, without an apparent increase [...]
“Great Unified Microscope” Reveals Hidden Micro and Nano Worlds Inside Living Cells
University of Tokyo researchers have created a powerful new microscope that captures both forward- and back-scattered light at once, letting scientists see everything from large cell structures to tiny nanoscale particles in a single shot. Researchers [...]
Breakthrough Alzheimer’s Drug Has a Hidden Problem
Researchers in Japan found that although the Alzheimer’s drug lecanemab successfully removes amyloid plaques from the brain, it does not restore the brain’s waste-clearing system within the first few months of treatment. The study suggests that [...]
Concerning New Research Reveals Colon Cancer Is Skyrocketing in Adults Under 50
Colorectal cancer is striking younger adults at alarming rates, driven by lifestyle and genetic factors. Colorectal cancer (CRC) develops when abnormal cells grow uncontrollably in the colon or rectum, forming tumors that can eventually [...]
Scientists Discover a Natural, Non-Addictive Way To Block Pain That Could Replace Opioids
Scientists have discovered that the body can naturally dull pain through its own localized “benzodiazepine-like” peptides. A groundbreaking study led by a University of Leeds scientist has unveiled new insights into how the body manages pain, [...]
GLP-1 Drugs Like Ozempic Work, but New Research Reveals a Major Catch
Three new Cochrane reviews find evidence that GLP-1 drugs lead to clinically meaningful weight loss, though industry-funded studies raise concerns. Three new reviews from Cochrane have found that GLP-1 medications can lead to significant [...]
How a Palm-Sized Laser Could Change Medicine and Manufacturing
Researchers have developed an innovative and versatile system designed for a new generation of short-pulse lasers. Lasers that produce extremely short bursts of light are known for their remarkable precision, making them indispensable tools [...]
New nanoparticles stimulate the immune system to attack ovarian tumors
Cancer immunotherapy, which uses drugs that stimulate the body’s immune cells to attack tumors, is a promising approach to treating many types of cancer. However, it doesn’t work well for some tumors, including ovarian [...]
New Drug Kills Cancer 20,000x More Effectively With No Detectable Side Effects
By restructuring a common chemotherapy drug, scientists increased its potency by 20,000 times. In a significant step forward for cancer therapy, researchers at Northwestern University have redesigned the molecular structure of a well-known chemotherapy drug, greatly [...]
Lipid nanoparticles discovered that can deliver mRNA directly into heart muscle cells
Cardiovascular disease continues to be the leading cause of death worldwide. But advances in heart-failure therapeutics have stalled, largely due to the difficulty of delivering treatments at the cellular level. Now, a UC Berkeley-led [...]
The basic mechanisms of visual attention emerged over 500 million years ago, study suggests
The brain does not need its sophisticated cortex to interpret the visual world. A new study published in PLOS Biology demonstrates that a much older structure, the superior colliculus, contains the necessary circuitry to perform the [...]
AI Is Overheating. This New Technology Could Be the Fix
Engineers have developed a passive evaporative cooling membrane that dramatically improves heat removal for electronics and data centers Engineers at the University of California San Diego have created an innovative cooling system designed to greatly enhance [...]
New nanomedicine wipes out leukemia in animal study
In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic. In the new study, [...]
