Newswise The most practical solution for drug delivery to the eyeball is topical, i.e. eye drops. However, a naturally occurring substance in tears actually can interact with the drug delivery system (DDS), hindering absorption of the drug and preventing it from getting into the cells it needs to target. Mucin, or MUC, is usually there to protect your eye, but when MUC is exposed to a molecule such as a lipoplex, a common form of DDS already used in ophthalmological drugs, it will bind to it and reduce absorption into the targeted tissue. So, scientists asked, is there some way to sneak the lipoplex past the MUC?

Through the use of an engineered, artificial protein corona (PC), researchers were able to dress the lipoplexes up as something that MUC would ignore. They found that a protein called Fibronectin (FBN), and a tripeptide of the amino acids Valine, Glycine, and Aspartate (VGA), were both effective at concealing the lipoplex, avoiding being coated in MUC, and binding to the corneal epithelial cells for better absorption of the DDS.

Because MUC binds to the lipoplex surface, it alters both their size and the positive or negative surface charge, explains Carlo Astarita, Ph.D. candidate studying at the Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University. This reduces absorption of the medicine by the primary corneal epithelial cells. So, how do we prevent MUC from interfering? We give the liposome a new coating that is recognized by receptors expressed on the ocular surface, circumventing the problem, and delivering the molecule more directly to the targeted tissue.

The researchers are part of a multi-institutional, international collaboration between the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University, the University of Pennsylvanias Scheie Eye Institute, and co-authors at several universities in Italy.

As a dry eye specialist I see a myriad of patients with various surface disease issues, says Giacomina Massaro, M.D., of the Scheie Eye Institute, Department of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania, and in order to achieve an effective treatment, drugs need to reach the target tissue (i.e. the corneal epithelial cells). In many situations the drugs are blocked by a complex mix of mucous, lipids, proteins and fluids which bathe the ocular surface. It is imperative that drugs have the ability to break through this barrier.

This study is a quintessential example of our researchers using precision medicine to innovate, says Antonio Giordano, M.D., Ph.D., Founder and Director of the Sbarro Health Research Organization (SHRO) and the Sbarro Institute at Temple University, as well as a joint research program with the University of Siena, Italy. We identify a problem which inhibits the efficacy of certain types of treatments, and then we ask, what does the body provide in this case as its own solution? In this case, the answer is right there on the surface of the cells: we make the medicine so that it binds with the targeted tissue. In this way, precision medicine opens the door to increased effectiveness to treat a wide range of ocular conditions and disease.

About the Sbarro Health Research Organization (SHRO)

The Sbarro Health Research Organization is a non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and related chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism (www.shro.org)

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The Medicine in Eye Drops Needs a Disguise to Sneak Past Your Tears - Newswise

New studies of the molecular action of tarantula venom on sodium channels may suggest ideas for the structural design of better drugs to treat chronic pain. The venom plunges a biochemical stinger into a voltage sensor on the channel that traps it in its resting position, keeping the channel from activating and from producing electrical signals. Credit: Alice C. Gray

Venom immobilizes prey by interfering with sodium channels that generate electrical signals in the animals nerve cells.

Oversized, hairy tarantulas may be unsightly and venomous, but surprisingly their hunter toxin may hold answers to better control of chronic pain.

A bird-catching Chinese tarantula bite contains a stinger-like poison that plunges into a molecular target in the electrical signaling system of their preys nerve cells.

A new high-resolution cryo-electron microscopy study shows how the stinger quickly locks the voltage sensors on sodium channels, the tiny pores on cell membranes that create electrical currents and generate signals to operate nerves and muscles. Trapped in their resting position, the voltage sensors are unable to activate.

The findings are published in Molecular Cell, a journal of Cell Press.

The action of the toxin has to be immediate because the tarantula has to immobilize its prey before it takes off, said William Catterall, professor of pharmacology at the University of Washington School of Medicine. He was the senior researcher, along with pharmacology professor and Howard Hughes Medical Institute investigator, Ning Zheng, on the study of the molecular damage inflicted by tarantula venom.

This graphic abstract for a Nov. 23 Molecular Cell paper shows how a tarantula nerve toxin acts on a chimera of a voltage-gated sodium channel. The chimeric sodium channel contains part of a human channel crucial for pain transmission that has been imported onto a model ancestral sodium channel from a bacterium. The tarantula toxin has a lysine stinger that traps the voltage sensor on the sodium channel and keeps it from activating. The toxin thus immobilizes the tarantulas prey. Its action on sodium channels also holds ideas for designs for better pain-control drugs. Credit: Catterall and Zheng labs/UW Medicine

While some might dismiss those tarantulas as ugly, tough and mean, medical scientists are actually interested in their venoms ability to trap the resting state of the voltage sensor on voltage-gated sodium channels and shut them down. Such studies of toxins from these big, nasty dudes, as Catterall describes them, could point to new approaches to structurally designing drugs that might treat chronic pain by blocking sensory nerve signals.

Catterall explained that chronic pain is a difficult-to-treat disorder. Efforts to seek relief can sometimes be a gateway to opiate overdose, addiction, prolonged withdrawal, and even death. The development of safer, more effective, non-addictive drugs for pain management is a vital need.

However, because it has been hard to capture the functional form of the tarantula toxin-ion channel chemical complex, reconstructing the toxins blocking method in a small molecule has so far eluded molecular biologists and pharmacologists seeking new ideas for better pain drug designs.

Researchers overcame this obstacle by engineering a chimeric model sodium channel. Like mythical centaurs, chimeras are composed of parts of two or more species. The researchers took the toxin-binding region from a specific type of human sodium channel that is crucial for pain transmission and imported it into their model ancestral sodium channel from a bacterium. They were then able to obtain a clear molecular view of configuration of the potent toxin from tarantula venom as it binds tightly to its receptor site on the sodium channel.

This achievement revealed the structural basis for voltage sensor trapping of the resting state of the sodium channel by this toxin.

Remarkably, the toxin plunges a stinger lysine residue into a cluster of negative charges in the voltage sensor to lock it in place and prevent its function, Catterall said. Related toxins from a wide range of spiders and other arthropod species use this molecular mechanism to immobilize and kill their prey.

Catterall explained the medical research importance of this discovery. The human sodium channel placed into the chimeric model is called the Nav1.7 channel. It plays an essential role, he noted, in transmission of pain information from the peripheral nervous system to the spinal cord and brain and is therefore a prime target for pain therapeutics.

Our structure of this potent tarantula toxin trapping the voltage sensor of Nav1.7 in the resting state, Catterall noted, provides a molecular template for future structure-based drug design of next-generation pain therapeutics that would block function of Nav1.7 sodium channels.

Reference: Structural Basis for High-Affinity Trapping of the NaV1.7 Channel in Its Resting State by Tarantula Toxin by Goragot Wisedchaisri, Lige Tonggu, Tamer M. Gamal El-Din, Eedann McCord, Ning Zheng and William A. Catterall, 23 November 2020, Molecular Cell.DOI: 10.1016/j.molcel.2020.10.039

The lead authors on the study were Goragot George Wisedchaisri and Lige Tonggu, both of the UW School of Medicine Department of Pharmacology. Tamer M. Gamal El-Din, also of Pharmacology, and Eedann McCord, now with the Department of Physiology and Biophysics at the UW medical school, contributed to the research.

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Tarantula Toxin Attacks With Molecular Stinger May Hold Answers to Better Control of Chronic Pain - SciTechDaily

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Combination therapies appear to prevent emergence of drug resistance

MD/PhD student Rita Chen (left) and Brett Case, PhD, a postdoctoral researcher, prepare to work with SARS-CoV-2, the virus that causes COVID-19, under strict biosafety conditions. Chen, Case and MD/PhD student Emma Winkler co-led a study with virologist and immunologist Michael S. Diamond, MD, PhD, at Washington University School of Medicine in St. Louis, to assess how well antibody-based drugs for COVID-19 perform against a range of virus variants.

COVID-19 therapies made from antibodies often are given to patients who are at high risk of severe illness and hospitalization. However, there have been nagging questions about whether such antibody therapies retain their effectiveness as worrisome new virus variants arise.

New research at Washington University School of Medicine in St. Louis suggests that many, but not all, therapies made from combinations of two antibodies are effective against a wide range of variants of the virus. Further, combination therapies appear to prevent the emergence of drug resistance.

The study, in mice and hamsters, tested all single and combination antibody-based therapies authorized for emergency use by the Food and Drug Administration (FDA), or that are being evaluated in late-stage clinical trials, against a panel of emerging international and U.S. variants of SARS-CoV-2, the virus that causes COVID-19.

The findings, published June 21 in the journal Nature, suggest that COVID-19 drugs made of two antibodies often retain potency as a therapy against variants even when in vitro studies experiments conducted in a dish indicate that one of the two antibodies has lost some or all ability to neutralize the variant.

We knew how these antibodies were behaving in vitro, but we dont give people drugs based solely on cell culture data, said senior authorMichael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine. When we looked in animals, there were some surprises. Some of the combinations performed better than we thought they would, based on in vitro data. And there was no drug resistance to combinations whatsoever, across all of the different variants. Were going to have to continue to monitor the effectiveness of antibody therapy as more variants arise, but combination therapy is likely needed for treating infections with this virus as more variants emerge.

So-called monoclonal antibodies mimic those generated by the body to fight off the virus that causes COVID-19. Administration of antibody therapies bypasses the bodys slower and sometimes less effective process of making its own antibodies. At the time this study began, there were two dual-antibody combination therapies and a single antibody therapy authorized by the FDA for emergency use. The FDA withdrew authorization for the single antibody therapy, bamlanivimab, in April on the grounds that it was not effective against the variants circulating at that time. In May, the FDA authorized the single antibody sotrovimab as a treatment for COVID-19.

In all, the researchers evaluated antibodies corresponding to the FDA-authorized ones made by Eli Lilly and Co., Regeneron and Vir Biotechnology/GlaxoSmithKline, as well as the antibodies currently under development by AbbVie, Vir and AstraZeneca that are in clinical trials.

The researchers led by co-first authors Rita E. Chen, an MD/PhD student, Emma S. Winkler, an MD/PhD student, and Brett Case, PhD, a postdoctoral researcher tested the antibodies against a panel of virus variants containing key mutations in their spike genes. The SARS-CoV-2 virus uses spike protein to invade cells. All monoclonal antibody-based COVID-19 therapies work by interfering with the interaction between spike protein and cells.

The panel included mutations found in three of the four variants that have been designated variants of concern by the World Health Organization Alpha (first identified in the United Kingdom), Beta (South Africa) and Gamma (Brazil) as well as an emerging variant from India similar to the Delta variant of concern. They also tested variants from New York and California. The researchers used a mix of virus samples originally obtained from people with COVID-19 and laboratory strains genetically engineered to contain key mutations.

The researchers evaluated the antibodies in hamsters and two strains of mice. The researchers first gave the animals antibodies singly or in the same combinations in which they are given to treat patients a day before infecting them with one of the virus variants. The researchers monitored the animals weight for six days and then measured the amount of virus in their noses, lungs and other parts of the body.

Although some single antibodies showed reduced or no ability to neutralize virus variants in a dish, low doses of most of the antibody combinations protected against disease caused by many of the variants. The researchers sequenced viral samples from the animals and found no evidence of drug resistance in viruses from any of the animals that had been treated with combination therapies.

Dual therapy seemed to prevent the emergence of resistant viruses, said co-author Jacco Boon, PhD, an associate professor of medicine, of molecular microbiology and of pathology & immunology. Resistance arose with some of the monotherapies, but never with combination therapy.

Since antibody-based COVID-19 therapies primarily are used to treat people who already are infected, the researchers also evaluated how well the antibody combinations performed when given after infection with the Beta variant. The Beta variant was chosen because it has been shown to be most likely to escape neutralization in laboratory-based experiments and has the most resistance to COVID-19 vaccines. The antibody cocktails corresponding to those from AstraZeneca, Regeneron and Vir were all effective at reducing disease caused by the Gamma variant; the one from AbbVie only was partially protective, and the one from Lilly showed no efficacy at all.

Its going to be useful going forward to understand how these monoclonal antibodies are going to behave as variants continue to emerge, said Diamond, who also is a professor of molecular microbiology and of pathology & immunology. We need to think about and generate combinations of antibodies to preserve our ability to treat this disease. And well need to monitor for resistance although, in my opinion, the use of specific combinations will make this less of an issue.

Chen RE, Winkler ES, Case JB, Aziati ID, Bricker TL, Joshi A, Darling T, Ying B, Errico JM, Shrihari S, VanBlargan LA, Xie X, Gilchuk P, Zost SJ, Droit L, Liu Z, Stumpf S, Wang D, Handley SA, Stine WB, Shi P-Y, Davis-Gardner ME, Suthar MS, Knight MG, Andino R, Chiu CY, Ellebedy AH, Fremont DH, Whelan SPJ, Crowe JE, Purcell L, Corti D, Boon ACM, Diamond MS. In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. Nature. June 21, 2021. DOI: 10.1038/s41586-021-03720-y

This study was supported by the National Institutes of Health (NIH), grant and contract numbers R01 AI157155, U01 AI151810, U01 AI141990, R01 AI118938, 75N93019C00051, HHSN272201400006C, HHSN272201400008C, and HHSN75N93019C00074; the Childrens Discovery Institute, grant number PDII2018702; the Defense Advanced Research Project Agency, grant number HR0011-18-2-0001; the Dolly Parton COVID-19 Research Fund at Vanderbilt University; Fast Grants; the Mercatus Center at George Mason University; and the Future Insight Prize from Merck KGaA.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, consistently ranking among the top medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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COVID-19 dual-antibody therapies effective against variants in animal study Washington University School of Medicine in St. Louis - Washington...

The GW4 Alliance (Bath, Bristol, Cardiff and Exeter universities GW4) formally launched their new One Health antimicrobial resistance research consortium this week [Wednesday 16 June]. The World Health Organisation cites antimicrobial resistance (AMR) as one of the most significant risks facing the world. AMR threatens global health and development as it impacts on human, animal and plant health and also our environment, water safety and food security.

The GW4 AMR Alliancehas been established to tackle this global challenge and become the UKs leading interdisciplinary One Health AMR research consortium, recognised worldwide.

A launch event showcasing GW4s cross-disciplinary AMR research collaborations and some of the One Health AMR projects and programmes being undertaken by GW4 teams and their collaborators took place on Wednesday [16 June] and included talks from University of Bristol researchers who discussed some of their latest findings from AMR research projects.

Antimicrobial resistance where bacterial, fungal, viral and parasitic infections become resistant to existing antimicrobial drugs is an increasing global societal threat, as there is no matching increase in new antibiotics or new therapies to help treat patients infections.

The COVID-19 pandemic has brought the pandemic of AMR into sharper focus. Antimicrobial use, which drives the emergence of AMR, increased in many intensive care units around the world, as clinicians mitigated the development of secondary bacterial and fungal infections in acutely ill hospitalised patients. AMR is a slower moving, silent pandemic but requires urgent action now to stop resistance expanding and find drugs to treat these infections.

The GW4 AMR Alliance builds on and enhances the GW4 universities strong and diverse portfolio of AMR research. Its vision is to tackle AMR using a One Health approach and to be the partner of choice for future AMR research consortia funding to help mitigate the urgent threat of AMR.

During the launch, Dr Kristen Reyher, leader of BristolsAMR Forceresearch group at Bristol Vet School, Matthew Avison, Professor of Molecular Bacteriology from Bristols School of Cellular and Molecular Medicine, and Helen Lambert, Professor of Medical Anthropology at Bristol Medical School, addressed AMR known unknowns as well as the link between climate change and AMR, and presented their latest research findings from projects in Thailand, Argentina and China.

Professor Avison, lead PI of the One Health Drivers of AMR in Thailand (OH-DART)project, discussed the key levers that could be pulled to help mitigate the threat of AMR in the country which, in 2010 was estimated to have caused 38,000 deaths and an economic loss of 1.2 billion US$ per year. This is mostly due to antibacterial resistance (ABR) which is common in bacteria isolated from humans, animals and the environment. He also discussed a recent paper modelling the impacts of antimicrobial usage changes in farming and human medicine.

Dr Reyher presented the latest findings from the Bristol-led One Health Selection and Transmission of Antimicrobial Resistance (OH-STAR) study and their implications for surveillance of AMR on farms, including advice about sampling from the same sites on farms, controlling for temperature in sampling and using a consistent sampling technique.

Professor Lambert, lead PI of the UK-China AMR Partnership Hub STAR-CHINA, discussed the social and cultural drivers which underpin the threat of AMR such as antibiotic prescribing and environmental exposure via water use practices, highlighting the need for interventions that alter AMR transmission pathways to take patterns of human behaviour into account.

Dr Timothy Jinks, Head of the Drug-Resistant Infections Programme at theWellcome Trust, who is delivering the keynote lecture, said: Containing and controlling AMR requires collaborative, long-term, interdisciplinary and sustainable research taking a global One Health approach. It is great news that the GW4 AMR Alliance is launching to increase understanding, development and implementation of effective interventions.

GW4s proven academic excellence in AMR research across disciplines and across institutions is demonstrated by a portfolio of AMR relevant research funding in excess of 40m.

Dr Joanna Jenkinson, GW4 Alliance Director, commented: Our strategic initiative is in total accord with the G7 Health Ministers recent communique (on 4 June) which outlined the need to act on the growing pandemic of AMR with clear leadership, bold science-based actions and a One Health approach, recognising and understanding that the health of humans, animals, plants and their shared environment are inextricably interlinked. The GW4 has fostered collaborative AMR projects at scale to achieve more than our institutions can individually. We are also proud to support our early career researchers (ECR) through our Crucible programme on Interdisciplinary Approaches to AMR and opportunities to apply for seed funding. We are delighted that one new ECR AMR community, further supported by our GW4 Generator Award funding scheme, is contributing a presentation at the launch today on their project to find new antibiotic leads.

AMR disproportionately affects low-and-middle income countries and the research being showcased today demonstrates our global reach with collaborative GW4 projects taking place in Thailand, China, Bangladesh, Argentina, India and here in the UK. GW4 researchers are exploring what drives the emergence of AMR in different settings e.g. the environment (particularly in aquatic systems from industrial and domestic waste), livestock farming, aquaculture and healthcare.

Identifying the drivers of AMR will help to help modify them by informing policy and implementing interventions to mitigate this rising threat. In the UK alone, there was a nine per cent increase in deaths caused by drug-resistant infections between 2017 and 2018.

Chair of the GW4 AMR Alliance, Prof Eshwar Mahenthiralingam (Cardiff University), said: This is a very exciting and timely consortium bringing the considerable AMR research strengths across the GW4 universities together to work as one cohesive unit to drive forward our understanding of, and to develop new interventions for containing and controlling AMR.

About the GW4 AMR Alliance

The GW4 Alliance Bath, Bristol, Cardiff and Exeter universities (GW4) are developing initiatives at scale that recognise the combined research strengths of the Alliance. The new GW4 AMR Alliance joins a number of global challenge research programmes (including climate) designed to foster new regional, national and global research partnerships to tackle major global challenges at scale.

The AMR Alliance is taking a One Health approach to tackle the growing threat of AMR. A 12-strong Steering Group draws together key members from the GW4s AMR research community to drive the programme forward, using cross-institutional, synergistic, interdisciplinary research that maximises engagement, translation and impact. The University of Bristol is represented by Professor Matthew Avison (School of Cellular and Molecular Medicine and Bristol AMR lead), Professor Helen Lambert (Bristol Medical School and UKRI Challenge Leader for Global Health) and Dr Kristen Reyher (Bristol Veterinary School).

About Bristol AMR

TheBristol AMRinterdisciplinary research network is led by a cross-faculty management committee comprising AMR research investigators from all six faculties.

Since 2015, the Bristol AMR research community has received 17.2 million of AMR research funding including grants awarded from the UKRI 'Tackling AMR A Cross-Council AMR initiative'. Funded projects include EPSRC BristolBridge, ESRC AMR Research Champion (Prof Helen Lambert) and three large consortium awards for AMR Themes 2 (BBSRC-led), 3 (NERC-led) and 4 (ESRC-led).

Bristol AMR investigators work across all disciplines to help tackle AMR, including the discovery of new antibiotics, the development of novel antimicrobial materials to prevent infection, rapid diagnostics for AMR, understanding behaviours to promote the responsible use of antimicrobials in healthcare and veterinary medicine, using data linkage to improve the use of antibiotics in healthcare and understanding how different regulatory systems in human and animal healthcare drive global AMR.

Bristol AMR investigators take a global One Health approach and work with collaborators across the UK and in low-and-middle income countries. Projects include an MRC/DoHSC 'AMR in a Global Context' award to study the drivers of AMR in Thailand; two MRC/Newton Fund UK-China Partnership Programmes to identify the key determinants of antimicrobial use and strategies to reduce the burden of AMR in China; a DoHSC GAMRIF/CONICET UK-Argentina awardlooking at future-proofing antibacterial resistance risk management surveillance and stewardship in the Argentinian farming environment; an MRC South Africa-UK Drug Discovery Partnership Hub to find new antibiotics from biodiverse-rich habitats and an EPSRC GCRF funded project to help develop nanoparticle based rapid diagnostics for tuberculosis with collaborators in Kenya.

Bristol also leads the 4 million Medical Research Foundation National PhD Training Programme in AMR Research to train next generation of AMR researchers through its multidisciplinary AMR studentships its national training cohort of 150 PhD students studying AMR across the UK.

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June: gw4amr-launch | News and features - University of Bristol

Bio-IT World Conference & Expo, September 20-22, 2021

NEEDHAM, Mass. (PRWEB) June 22, 2021

Bio-IT World Conference & Expo has just released the final agenda for the 20th anniversary eventtaking place virtually and in-person on September 20-22, 2021 in Boston, Mass.featuring a comprehensive list of 180+ biopharma executives along with other industry experts.

Bio-IT World Conference & Expo will return this year to Boston, Mass., once again bringing a diverse lineup of speakers and an expo with leading solution providers to its new venue, the Sheraton Boston. The hybrid format also features a virtual platform that provides an option for biopharma leaders from around the world to engage with their peers and expert thought leaders safely and conveniently.

Bio-IT World continues taking a leadership role to keep our life science community connected. We are investing in technology to ensure you stay connected with others whether you attend in-person or virtually. We are grateful for the support of our community during the past year as we pivoted from an in-person meeting in 2019, to a 100% virtual meeting in 2020, and now to a hybrid format for 2021. We are excited to see you at our new venue in Boston and look forward to hearing the latest research, science, and solutions, said Bio-IT World Executive Event Director, Cindy Crowninshield.

Biopharma executives who will be sharing their thought leadership this September include:

Attend Bio-IT World Conference & Expo this September 20-22, 2021, at the Sheraton Boston in Boston, Mass. In-person space is limited this year. Register today to secure your spot: bio-itworldexpo.com.

About Bio-IT World Conference & ExpoFor 20 years, the Bio-IT World Conference & Expo has been the worlds premier event showcasing technologies and analytic approaches that solve problems, accelerate science, and drive the future of precision medicine. Bio-IT World unites a community of leading life sciences, pharmaceutical, clinical, healthcare, informatics and technology experts in the field of biomedical research, drug discovery & development, and healthcare from around the world.

For sponsorship opportunities contact Angela Parsons, VP, Business Development at aparsons@healthtech.com.

To register to attend Bio-IT World Conference & Expo, click here.

About Cambridge Healthtech InstituteCambridge Healthtech Institute (CHI), a division of Cambridge Innovation Institute, is the preeminent life science network for leading researchers and business experts from top pharmaceutical, biotech, CROs, academia, and niche service providers. CHI is renowned for its vast conference portfolio held worldwide including PepTalk, Molecular Medicine Tri-Conference, SCOPE Summit, Bio-IT World Conference & Expo, PEGS Summit, Drug Discovery Chemistry, World Pharma Week, The Bioprocessing Summit, Next Generation Dx Summit, Immuno-Oncology Summit, and Discovery on Target. CHI's portfolio of products includes Cambridge Healthtech Institute Conferences, Barnett International, Insight Pharma Reports, Bio-IT World, Clinical Research News and Diagnostics World. For more information visit healthtech.com.

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Long-term and deep reprogramming of immune cells

The immune systems response to infection with SARS-CoV-2 has a significant impact on the course of COVID-19 and an overactive immune response is responsible for many serious complications. A new study demonstrates the far-reaching changes that the virus causes in the innate immune system.

The research team about the first author d. Sebastian Theobald of the University Hospital Cologne examined the effect of the spike protein, a typical feature of the coronavirus, on the innate immune system. It turns out that SARS-CoV-2 infection causes profound and long-term reprogramming of macrophages, the researchers wrote. The results of the corresponding study were published in the specialized journal .EMBO Molecular Medicine.

According to the researchers, the reason why some people with an excessive immune response to SARS-CoV-2 are still not well understood. Clearly, SARS-CoV-2 infection can lead to a massive release of inflammatory signaling substances, called cytokines, that cause severe organ damage in some infected people and lure active defense cells in tissues into a chain reaction. . How the virus releases cytokines has not been clearly established.

For the first time, researchers were able to demonstrate the effect of the spike protein on the innate immune system and found that human defense cells (macrophages, also called scavenger cells) are highly stimulated by the viral spike protein to produce the inflammatory signaling substance. interleukin 1.

However, this was only the case if the macrophages of people with COVID-19 were examined in the trials. The researchers reported that macrophages from people who had not yet been in contact with SARS-CoV-2 did not react by releasing interleukin-1.

Dr. confirms. Jan Riebniker, Head of the Infectious Disease Research Laboratory at the University Hospital Cologne. The expert also sees many starting points here to understand why some people react with an overreaction of the immune system.

Interestingly, macrophages can still be very strongly activated by the sparse protein several weeks to months after SARS-CoV-2 infection. Because macrophages have a very short lifespan of only a few days, this indicates changes in the DNA of the macrophage progenitor cells, explains Dr. Sebastian Theobald. The researchers were also able to demonstrate so-called epigenetic changes through complex sequencing experiments.

The research team continues that profound changes from macrophages to the genetic makeup of cells can now also be used to better understand the long-term consequences of COVID-19. Last but not least, the results of the study are also important in relation to vaccines, as the spike protein plays a major role in these vaccines.

For the success of different vaccine formulations, it is certainly beneficial that the spike protein leads to a strong activation of the innate immune system, says Riebnecker.

In addition, the inflammatory signaling pathway investigated here, which ultimately leads to the release of interleukin-1, is also a potential therapeutic starting point for immune-modulating therapies in severe COVID-19 cycles, and the study provides a scientific basis for this. (fp)

This text complies with the requirements of the specialized medical literature, clinical guidelines and current studies and has been examined by medical professionals.

swell:

important note:This article is for general guidance only and is not intended to be used for self-diagnosis or self-treatment. It cannot replace a visit to the doctor.

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The innate immune system has been deeply reprogrammed - the practice of healing - BioPrepWatch