Synthetic Nanobody Potential Treatment, Red Marrow Main Target, Europe Source Of Spread: COVID-19 Updates

November 6, 2020 I Isolated cannabis compounds decrease cytokines, spike protein disrupts blood-brain barrier, aprotinin potential treatment, D614F mutation made virus more contagious, seven forms of disease identified, and new nanoparticle vaccine a promising candidate. Plus: Cornea of the eye may be resistant, propranolol reduces inflammation, autoimmune antibody culprit for blood clots, and lung damage found in ‘long COVID’.

Research News

A new synthetic nanobody, called sybody 23, has been identified as a potential treatment for COVID-19. A technology platform to select sybodies from large synthetic libraries was used to identify which ones could block SARS-CoV-2 from infecting human cells. Researchers from the European Molecular Biology Laboratory analyzed sybody 23 based on its stability, effectiveness, and precision of binding and found it to be particularly effective at blocking receptor-binding domains (RBDs). To confirm its effectiveness against SARS-CoV-2, the group used a lentivirus that had been modified so that it carried the SARS-CoV-2 spike protein on its surface. They observed that sybody 23 successfully disabled the modified virus in vitro. The authors of this study, published in Nature Communications, say that additional tests are needed to confirm whether this sybody can block COVID-19 infection in human cells. DOI:10.1038/s41467-020-19204-y

Researchers at the University of Huddersfield and University of Minho in Portugal have carried out one of the largest analyses of its kind on 27,000 virus genomes from around the world to map out the dispersal of SARS-CoV-2. They discovered that the spread of the virus to America and other parts of the world was largely linked to Europe, not China. They did find that the virus originated in China, likely transmitted from horseshoe bats to humans. Their research also suggests that travel restrictions across Britain and Europe were implemented too late. The group’s findings are published in Microorganisms. DOI:10.3390/microorganisms8111678

The cornea of the eye may be resistant to COVID-19, a new study published in Cell Reports has found. Researchers from Washington University School of Medicine report that every donor cornea that they tested was resistant to the virus and did not support growth. While some SARS-CoV-2 patients do experience eye symptoms, such as conjunctivitis, the researchers believe this may be related to secondary inflammation and not the virus itself. The team cautions that eye protection should still be worn until further research is done on SARS-CoV-2 effects on tears ducts and the conjunctiva. DOI:10.1016/j.celrep.2020.108339

A new study led at Brigham and Women’s Hospital has uncovered a subset of recovered COVID-19 patients that sustain antibodies for several months post-infection. The research team recruited and enrolled 92 participants in the Boston area who had recovered from the virus between March and June 2020. They collected and analyzed blood samples monthly, measuring a range of antibodies which included IgG. They found that in a subset of these individuals (roughly 20%), virus-specific IgG production remained stable or enhanced over the course of three to four months, compared to the other recovered patients that had declining levels of this antibody. These “sustainers” also had symptoms for a significantly shorter period of time when compared to the other participants (10 days vs 16 days, respectively). The authors of this study, published in Cell, noted that one limitation to this research was that most of the volunteers were adult white females. DOI:10.1016/j.cell.2020.10.051

Researchers have identified unique characteristics in the lungs of those suffering from ‘long COVID’. The study, published in eBioMedicine, analyzed the organs of 41 patients who died from COVID-19 at the University Hospital of Trieste, Italy from February to April 2020, examining lung, heart, liver, and kidney samples. The research team, led by King’s College London, found extensive lung damage in most cases and profound disruption of the normal lung structure. Nearly 90% of the patient lung samples showed extensive blood clotting in the lung arteries and veins and several lung cells were abnormally large. Additionally, the samples showed persistence of the viral genome in respiratory cells and in cells lining the blood vessels that persisted for several weeks or months. They believe these findings could explain ‘long COVID’. The study found no obvious signs of SARS-CoV-2 infection or prolonged inflammation in other organs. DOI:10.1016/j.ebiom.2020.103104

Beta-blockers could be a potential treatment for reducing inflammation in COVID-19 patients, finds a team of researchers led at the University of South Australia. The researchers found evidence in animal models that the beta-blocker Propranolol suppressed the spread of cancer in the lungs, which has a similar inflammatory profile to COVID-19. The Australian and Italian research team has called for clinical trials to further investigate this potential SARS-CoV-2 treatment and their findings are published in Frontiers of Immunology. DOI:10.3389/fimmu.2020.588724

An autoimmune antibody may be the cause of COVID-19 blood clots, according to new research published in Science Translational Medicine. The study led at Michigan Medicine identified this blood-clotting antibody in about half of hospitalized COVID-19 patients that is typically seen in patients with the autoimmune disease antiphospholipid syndrome. These patients with severe COVID-19 also had high levels of super-activated neutrophils, which destruct white blood cells. Researchers studied the activated neutrophils and those antibodies found in COVID-19 patients on mouse models and discovered a very high level of clotting in those animals. The team now aims to determine if blocking these antibodies in severely ill patients proves better outcomes and for how long these antibodies remain in circulation after recovery. DOI:10.1126/science.abd3876

Seven different “forms of disease” have been identified in mild COVID-19 cases, finds a team of Medical University of Vienna scientists. The study, published in Allergy, involved 109 convalescent individuals and 98 health individuals for their control group. Researchers were able to determine seven different groups of symptoms, which distinguished systemic from organ-specific forms of disease. The scientists also found that the virus leaves behind detectable changes in the blood that is similar to a fingerprint. The number of granulocytes were significantly lower in the COVID-19 group and regulatory cells were greatly diminished, which the study emphasizes could lead to autoimmunity. Essentially, their findings show that the immune system “doubles up” when fighting COVID-19 even several weeks after infection. They hope to implement these findings for development of a highly effective vaccine. DOI:10.1111/all.14647

University of Pittsburgh School of Medicine scientists have developed a rapid method to identify potent, neutralizing monoclonal antibodies against COVID-19, particularly the antibody called “Ab1”. The team collected blood samples from a few hundred people and built multiple libraries containing 1 trillion human antibodies. When the pandemic first appeared, the researchers panned their libraries to find the most promising candidates and discovered Ab1, which is a fully human monoclonal antibody that proves to be highly effective at preventing and treating COVID-19 in animal models. This antibody is on track for human clinical trials by early next year. This method of panning for antibodies, rather than waiting for people to become infected and recover to make antibodies, shows promise to become a fast and efficient method, say authors of the study published in the Proceedings of the National Academy of Sciences. DOI:10.1073/pnas.2010197117

A new vaccine candidate, designed by scientists at the University of Washington School of Medicine in Seattle, produces virus-neutralizing antibodies in mice at levels ten-times higher than seen in people recovered from COVID-19. The vaccine candidate was developed using structure-based vaccine design techniques invented at UW Medicine and is a self-assembling protein nanoparticle. This new vaccine candidate can be given at relatively low doses and shows a strong B-cell response after immunization, which may provide long lasting protection against the virus. The vaccine has been transferred to two companies for clinical development. This preclinical data is published in Cell. DOI:10.1016/j.cell.2020.10.043

Estonian researchers in University of Tartu explain how SARS-CoV-2 is activated before attacking cells and what could potentially curb its aggressive nature. The study, published in Scientific Reports, compared the cell entry mechanisms of the virus to other coronaviruses and MERS-CoV, focusing on the spike protein. They discovered that the enzyme furin efficiently cleaved the SARS-CoV-2 spike protein motif, while furin failed to cleave the motifs in the other viruses studied. Given that furin is expressed throughout the human body, the range of cells the virus can enter is vast and may explain why COVID-19 is particularly aggressive. These findings confirm that furin inhibitors may block SARS-CoV-2 replication and have therapeutic effects against the virus. DOI:10.1038/s41598-020-74101-0

A new study, published in mBio, identifies a SARS-CoV-2 mutation, called D614G, that may have made the virus more contagious. Houston Methodist Hospital and University of Texas (UT) at Austin researchers studied virus mutations in more than 5,000 COVID-19 patients in Houston and found that during the initial wave of the pandemic, 71% of the Houston patients had this mutation and 99.9% during the second wave. These findings align with other studies done around the world, and two theories have come into play to explain why strains of the virus containing this mutation outcompeted the others. One UK study found that viruses with this mutation transmitted faster than those without it, and natural selection would favor strains that transmit the easiest. A second theory suggests another explanation, called “founder’s effects”, which essentially means this strain of the virus simply got a head start on other strains. The Methodist Houston-UT Austin team also noted 285 mutations across thousands of infections, although most do not seem to have a significant effect on severity of COVID-19 infection, and ongoing studies are monitoring the third wave of SARS-CoV-2. DOI:10.1128/mBio.02707-20

The main target for SARS-CoV-2 may be red marrow, leading to damage of erythrocytes and blocking the formation of new ones, according to new research published in Archiv EuroMedica. The study analyzed lung samples from 79 COVID-19 patients who died from the virus. They found damage to the endothelium of red marrow, which normally regulates the migration of maturing blood cells, and these damaged red blood cells led to ischemia and anemia with cell death of various organ systems. The researchers suggest erythrocyte mass and vitamin B12 as effective treatment options and note that mechanical ventilation is ineffective when there are not enough red blood cells to transport oxygen throughout the body. The mechanism of recovery of damaged erythrocytes remains unknown. DOI:10.35630/2199-885X/2020/10/3.1

An international team of researchers have identified aprotinin as a potential treatment for COVID-19. The research team found that the protease inhibitor drug blocks the entry of SARS-CoV-2 into host cells and may compensate for the loss of host cell protease inhibitors that are downregulated with COVID-19 infection. Aprotinin aerosols are already approved in Russia for influenza treatment, and the researchers believe it may have a particular potential to prevent severe COVID-19 disease when given early after diagnosis. These findings are published in Cells. DOI:10.3390/cells9112377

Temple University scientists have discovered that SARS-CoV-2 spike proteins disrupt the blood-brain barrier. The new study, published in Neurobiology of Disease, investigated the effects of the viral spike protein on brain endothelial cells in cell culture models. The research team found that introduction of the spike protein produced substantial changes that increased barrier permeability and impacted blood-brain barrier function, lending to an increased risk of invasion of SARS-CoV-2 in the brain. The long-lasting effects of these changes in blood-brain barrier function with COVID-19 infection are not known. The researchers also included that neurological damage could be greater in patients with pre-existing health conditions, like hypertension and dementia, in which the brain vasculature has already sustained some injury. DOI:10.1016/j.nbd.2020.105131

Industry News

PlantEXT and Israel’s Agricultural Research Organization (ARO) have isolated cannabis compounds that decrease pro-inflammatory cytokines in lung epithelial cells. Their research compared the effects of dexamethasone, which achieved an 80% reduction of IL-8, IL-6 and TNF-alfa when applied to biopsies of colon tissue taken from Inflammatory Bowel Disease patients, to certain cannabis-derived substances that showed comparable or better results on IL-6 and IL-8 reductions. They then investigated these specific compounds on lung epithelial cells and found the same reduction in pro-inflammatory cytokines. Initial research did find, however, that unprocessed cannabis had a potentially harmful effect that caused up to a 400-fold increase in the production of IL-6 and IL-8. Along with mitigating symptoms of COVID-19, the company is investigating potential pharmaceutical cannabis to prevent and treat lung inflammation related to the virus. Press Release

The U.S Department of Energy’s (DOE) Office of Technology Transitions (OTT) has announced a COVID-19 Technical Assistance Program (CTAP) that provides funding for national laboratory researchers to assist U.S. entities on COVID-19 projects. CTAP funding is for technical assistance of limited duration and scope, and CTAP-funded projects are not meant to be research and development intensive. Press Release