Lilly and Sitryx Announce Licensing and Research Collaboration to Discover and Develop New Immunometabolic Medicines – Yahoo Finance

INDIANAPOLIS and OXFORD, England, March 31, 2020 /PRNewswire/ --Eli Lilly and Company (NYSE: LLY) today announced an exclusive global licensing and research collaboration with Sitryx, a biopharmaceutical company focused on regulating cell metabolism to develop disease-modifying therapeutics in immuno-oncology and immuno-inflammation. The collaboration will study up to four novel preclinical targets identified by Sitryx that could lead to potential new medicines for autoimmune diseases.

"As Lilly seeks to develop new and unique medicines for people suffering with autoimmune diseases, we are actively exploring a variety of scientific approaches both in our own labs and with external partners," said Ajay Nirula, M.D., Ph.D., vice president of immunology at Lilly. "Regulating the metabolism of immune cells is a promising approach to treating these diseases, and we look forward to working with the talented researchers at Sitryx to advance their novel immunometabolism targets."

"We are excited to partner with Lilly, one of the global leaders in the field of immunology, to pursue the discovery of novel targets and the development of innovative therapies for autoimmune and inflammatory diseases in the fast-emerging area of immunometabolism," said Neil Weir, Ph.D.,chief executive officer of Sitryx. "This agreement is transformational for Sitryx and further validates the strength of our scientific expertise and that of our Founder network and the potential for Sitryx to become a leader in this field."

Under the terms of the agreement, Sitryx will receive an upfront payment of $50 million and Lilly will make a $10 million equity investment in Sitryx. Sitryx will be eligible to receive potential development milestones up to $820 million, as well as commercialization milestones and royalty payments on potential sales in the mid- to high-single digit range. In return, Sitryx will grant Lilly an exclusive, worldwide license to develop and commercialize up to four novel immunometabolism targeted therapeutics, including Sitryx's two lead projects. Lilly and Sitryx will establish a 5-year research collaboration to support the development of the therapeutics, with Sitryx responsible for drug discovery, while Lilly will fund and manage the clinical development and commercial phase of the collaboration.

This transaction is subject to customary closing conditions. The transaction will be reflected in Lilly's reported results and financial guidance according to Generally Accepted Accounting Principles (GAAP). There will be no change to Lilly's 2020 non-GAAP earnings per share guidance as a result of this transaction.

About SitryxSitryx is a biopharmaceutical company focused on regulating cell metabolism to develop disease-modifying therapeutics in immuno-oncology and immuno-inflammation. Sitryx's proprietary science is led by a highly experienced management team and supported by world class academic founders. Sitryx was founded by six world-leading researchers in the field of immunology and metabolism; Houman Ashrafian, Luke O'Neill, Jonathan Powell, Jeff Rathmell, Michael Rosenblum and Paul Peter Tak. Together they have published more than 1,000 papers in the field, making multiple key breakthroughs in our understanding of how critical energetic status is to the behavior of immune cells and in the broader field of immunology. In 2018, Sitryx raised $30 million Series A funding from an international syndicate of specialist investors including SV Health Investors, Sofinnova Partners, Longwood Fund and GSK. The company has a pipeline of projects at multiple stages of drug discovery. Sitryx is headquartered in Oxford, UK. For more information, please visit http://www.sitryx.com.

AboutEli Lilly and CompanyLilly is a global healthcare leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us atwww.lilly.com. C-LLY

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Lilly Forward-Looking StatementThis press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about the benefits of a collaboration between Lilly and Sitryx, and reflects Lilly's current beliefs. However, as with any such undertaking, there are substantial risks and uncertainties in the process of drug development and commercialization. Among other things, there can be no guarantee that Lilly will realize the expected benefits of the collaboration, or that the collaboration will yield commercially successful products. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

Refer to:

Mark Taylor; mark.taylor@lilly.com; (317) 276-5795 (Lilly Media)

Kevin Hern; hern_kevin_r@lilly.com; (317) 277-1838 (Lilly Investors)

Consilium Strategic Communications; +44 (0)20 3709 5700 (Sitryx)

Eli Lilly and Company logo. (PRNewsfoto/Eli Lilly and Company)

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RAPT Therapeutics Reports Fourth Quarter 2019 Financial Results and Provides Business UpdateCompany bolsters cash by $116 million with public…

SOUTH SAN FRANCISCO, Calif., March 30, 2020 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc.(Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical companyfocused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, today reported financial results for the fourth quarter ended December 31, 2019 and provided an update on recent operational and business progress.

2019 was an especially productive year for RAPT with the completion of our initial public offering and the generation of encouraging early clinical data for our two lead immunology-based programs: FLX475 for the treatment of multiple cancers and RPT193 for the treatment of atopic dermatitis and other allergic inflammatory diseases, said Brian Wong, M.D., Ph.D., President and CEO of RAPT Therapeutics. In addition, we partnered with Hanmi for FLX475 in Asia, a region with a high prevalence of charged tumors, and we strengthened our balance sheet substantially with our follow-on offering in February 2020.

Dr. Wong continued, For our ongoing Phase 1/2 study of FLX475, we continue to enroll and treat patients with multiple types of advanced cancer, though we are monitoring the impact of COVID-19 on our clinical trial sites both within and outside of the U.S. Because of the life-threatening nature of the cancers, we are working site by site to ensure that patients receive treatment and follow up as close to protocol-specified intervals as feasible. Our primary objective is patient safety and we will adapt to local circumstances as needed.

For RPT193, we successfully completed the healthy volunteer portion of the study. We have made the decision to pause the enrollment of patients with atopic dermatitis in the Phase1b portion of our clinical study for RPT193 in an effort to support clinicians and healthcare facilities that are prioritizing the fight against COVID-19, while safeguarding the health and safety of patients and clinicians who would be involved in our trial. We intend to resume enrollment as soon as practical once we expect patients can be treated and followed up consistently under safer public health conditions.

Financial Results for the Fourth Quarter and Full Year Ended December 31, 2019

Fourth Quarter Ended December 31, 2019Net loss for the fourth quarter of 2019 was $13.2 million, compared to $9.4 million for the fourth quarter of 2018.

Research and development expenses for the fourth quarter of 2019 were $10.2 million, compared to $8.4 million for the same period in 2018. The increase was primarily due to clinical costs related to the advancement of RPT193 and FLX475 as well as the personnel costs associated with these studies offset by outsourced research and development and lab supplies.

General and administrative expenses for the fourth quarter of 2019 were $2.6 million, compared to $1.3 million for the same period in 2018. The increase was due to an increase in consulting costs as well as accounting and audit-related costs as well as other expenses associated with being a public company.

Full Year Ended December 31, 2019Net loss for the year ended December 31, 2019 was $43.0 million, compared to $36.1 million for the same period in 2018.

Research and development expenses for the year ended December 31, 2019 were $34.9 million, compared to $31.8 million for the same period in 2018. The increase was primarily due to increases in costs relating to the clinical development of RPT193 and FLX475, facilities and personnel, offset by decreases in costs relating to lab supplies and outsourced research and development.

General and administrative expenses for the year ended December 31, 2019 were $8.7 million, compared to $5.2 million for the same period in 2018. The increase was primarily due to increases in professional service fees related to preparations for our initial public offering.

As of December 31, 2019, we had cash and cash equivalents of $77.4 million. In February 2020, we received net proceeds of approximately $69.7 million resulting from our follow-on public offering of 2,500,000 shares of common stock.

AboutRAPT Therapeutics, Inc.RAPT Therapeutics is a clinical stage immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases. Utilizing its proprietary discovery and development engine, the Company is developing highly selective small molecules designed to modulate the critical immune drivers underlying these diseases. RAPT has discovered and advanced two unique drug candidates, FLX475 and RPT193, each targeting C-C motif chemokine receptor 4 (CCR4), for the treatment of cancer and inflammation, respectively. The Company is also pursuing a range of targets, including general control nonderepressible 2 (GCN2) and hematopoietic progenitor kinase 1 (HPK1), that are in the discovery stage of development.

Forward-Looking StatementsThis press release contains forward-looking statements. These statements relate to future events and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future performances or achievements expressed or implied by the forward-looking statements. Each of these statements is based only on current information, assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties. Forward-looking statements include, but are not limited to, statements about the impact of COVID-19 on the clinical development of FLX475 and RPT193 and the anticipated timing of clinical data. Detailed information regarding risk factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in RAPTs Form 10-K expected to be filed with the Securities and Exchange Commission on or about March 30, 2020 and subsequent filings made by RAPT with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. RAPT disclaims any obligation to update these forward-looking statements.

RAPT Media Contact:Angela Bittingmedia@rapt.com(925) 202-6211

RAPT Investor Contact:Sylvia Wheelerswheeler@wheelhouselsa.com

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RAPT Therapeutics Reports Fourth Quarter 2019 Financial Results and Provides Business UpdateCompany bolsters cash by $116 million with public...

Mastercard-sponsored therapeutics accelerator awards $20 million gr… – Finextra

Today, the partners in the COVID-19 Therapeutics Accelerator announced grants of $20 million to three institutionsthe University of Washington, University of Oxford, and La Jolla Institute for Immunologyto fund clinical trials in order to identify highly potent immunotherapies for the COVID-19 pandemic.

These grants to leading institutions in their fields will advance our understanding of how existing drugs and antibodies can contribute to addressing the pandemic were facing around the world, said Mark Suzman, chief executive officer of the Bill & Melinda Gates Foundation. These initial investments through the COVID-19 Therapeutics Accelerator will bring rigor to the study of these potential solutions. The way forward will be informed by sound science and shared data.

In addition, newly announced funding from government and philanthropic donors has added to the Accelerators initial funding. The Chan Zuckerberg Initiative committed $25 million and the U.K. government committed 40 million last week. The additional funds will allow the Accelerator to continue making grants to study repurposed drugs and investigate biological compounds for activity against COVID-19. More funding is needed to move promising therapies through development and scale-up.

Studying repurposed drugs to prevent infection

Two of the newly announced trials will fund an investigation of two well-established drugs, hydroxychloroquine and chloroquine, that have known antiviral properties. These drugs have been used to treat malaria and a variety of rheumatological conditions for more than 50 years. The trials aim to determine whether the drugs are effective as pre- and post-exposure preventive therapy for COVID-19. While these drugs both show initial promise, rigorous scientific evidence is needed to make decisions on how, where and within which populations to use them in this pandemic.

The University of Washington will conduct a multi-site clinical trial in Western Washington and the New York City area, in collaboration with New York Universitys School of Medicine, investigating whether hydroxychloroquine can effectively prevent COVID-19 in people already exposed to the infection. The trial will enroll up to 2,000 asymptomatic men and women who are close contacts of persons with confirmed or pending COVID-19 diagnoses. Participants will be randomly assigned to take hydroxychloroquine or a placebo over two weeks, and samples will be collected and tested daily to confirm new COVID-19 infections across the two groups. Sandoz, a Novartis division, has donated the hydroxychloroquine doses needed to conduct the study. Participant enrollment will begin in April, and results will be available in late 2020.

The Mahidol Oxford Tropical Medicine Research Unit (MORU) will lead a placebo-controlled prophylaxis study of chloroquine and hydroxychloroquine in preventing COVID-19 in at-risk health care workers, frontline staff, and other high-risk groups. At least 40,000 participants in Asia and Europe will be randomized to receive either chloroquine (East Asian countries), hydroxychloroquine (United Kingdom and Europe), or a matched film-coated placebo as daily prophylaxis for three months. The one-year project, known as COPCOV, aims to determine definitively whether these drugs can prevent COVID-19 and thus protect the vital health care workforce. Participant enrollment will begin in April and initial results will be available by the end of the year.

Nick Cammack, COVID-19 Therapeutics Accelerator Lead at Wellcome, said: Investment in research is the worlds only exit strategy from COVID-19. Drugs, vaccines, and diagnostics are vital to saving lives, to ending this pandemic, and to preventing it from happening again. Now is the time to evaluate whether existing drugs will prove to be safe and effective. We urge others to join us in this collective global effort. Investing now, at scale, in the COVID-19 Therapeutics Accelerator is vital if we are to change the course of this pandemic.

Advancing immunological therapies

In addition to funding drug trials, the Accelerator will provide $1.73 million to the La Jolla Institute for Immunology to establish a Coronavirus Immunotherapy Consortium, known as CoVIC. The effort will bring together scientists from around the world and enable them to share and evaluate candidate antibodies side by side in a blinded, multidisciplinary analysis to identify ideal therapeutic combinations. Antibody therapies can be used to protect frontline health care workers, contacts, and others who are exposed, as well as treat those who have already become sick.

Todays grants are an important next step in the Therapeutic Accelerators commitment to identifying and scaling treatments to combat COVID-19, said Mike Froman, vice chairman of Mastercard. In order to provide therapeutic solutions to this global pandemic, particularly for those most vulnerable, we need to speed up the research and development process through a collaborative funding effort by the private sector, philanthropic organizations, and governments. We welcome the participation of additional organizations that can contribute the resources needed to help bring an end to this crisis.

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Mastercard-sponsored therapeutics accelerator awards $20 million gr... - Finextra

Collaboration initiated to develop COVID-19 immunotherapy – Drug Target Review

The University of Georgia and CEL-SCI Corporation have partnered to develop an immunotherapy to combat the COVID-19 coronavirus using the Ligand Antigen Epitope Presentation System (LEAPS) technology.

A collaboration between the University of Georgias (UGAs) Center for Vaccines and Immunology, US, and CEL-SCI Corporation has been formed to develop a Ligand Antigen Epitope Presentation System (LEAPS) COVID-19 immunotherapy. The immunotherapy candidate aims to treat patients at highest risk of dying from the novel coronavirus.

According to the new partners, the work will commence with pre-clinical studies based on experiments previously conducted with the LEAPS immunotherapy platform in collaboration with the US National Institutes for Allergies and Infectious Diseases (NIAID) against another respiratory virus, influenza A (H1N1). Those successful studies demonstrated that LEAPS peptides, given after virus infection has occurred, reduced morbidity and mortality in mice infected with H1N1.

It is suggested, based on studies with H1N1, that a LEAPS coronavirus SARS-CoV-2 immunotherapy may reduce or prevent the progression of the viral infection and prevent tissue damage from inflammation resulting from lung infiltration by the virus. By stimulating the correct immune responses without producing unwanted inflammatory responses associated with lung tissue damage, LEAPS immunotherapy may be particularly beneficial in those patients who are at highest risk of dying from COVID-19.

a LEAPS coronavirus SARS-CoV-2 immunotherapy may reduce or prevent the progression of the virus infection

The studies will utilise the LEAPS peptide approach that elicits both a cell-mediated antiviral response and an anti-inflammatory immunomodulating response by activating CD8 T lymphocytes. Previous studies showed that LEAPS immunogens can prevent lethal infection by herpes simplex virus (HSV) and H1N1 and stop the inflammatory disease progression of rheumatoid arthritis in animal models. LEAPS peptides against HSV demonstrated that the T-cell response was sufficient to prevent viral disease and if there was residual virus production, anti-viral antibodies were generated to further control the spread of the virus.

The proposed LEAPS peptides for the COVID-19 study are directed towards antigens within the NP protein of SARS-Cov-2 virus that elicit cytolytic T-cell responses. Unlike the viral glycoprotein Spike antigens, which are important for antibody-based vaccines, these NP-antigens are less variable between viral strains and less likely to change in response to antibodies elicited by prior infection or other vaccines. Cytolytic T-cell responses attack the virus infected cellular factories within the infected host in order to eliminate the source of virus and help subdue the infection.

We are eager to commence these studies, which if successful, may lead to clinical trials in humans to address the immediate and critical need to treat COVID-19 in the most vulnerable patients. We are very pleased and honoured to partner with Dr Ted Ross and his team and the UGA Center for Vaccines and Immunology. Their world-renowned expertise and world-class facilities will accelerate the development of LEAPS COVID-19 immunotherapy, stated CEL-SCI Chief Executive Officer Geert Kersten.

Dr Ross commented: LEAPS has the potential to be a powerful tool against SARS-CoV-2, the causative agent of COVID-19, based on its dual anti-viral and anti-inflammatory properties. Combining the prior pre-clinical data of LEAPS against H1N1 with our advancing knowledge of COVID-19, we aim to rapidly evaluate this technologys potential to meet the urgent need to treat patients at greatest risk of dying from this global pandemic. UGSs biocontainment labs at the Center for Vaccines and Immunology are ideally suited for these studies and will serve as critical assets in this collaboration with CEL-SCI.

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Collaboration initiated to develop COVID-19 immunotherapy - Drug Target Review

How to prevent overwhelming hospitals and build immunity – Harvard Gazette

The research indicates that one possible method for dealing with the epidemic amid a lack of other effective interventions may be multiple intermittent social-distancing periods that ease up when cases fall to a certain level and then are reimposed when they rise past a key threshold. The exact numbers, the work showed, depend on whether COVID-19 is a seasonal ailment like the flu and common cold also caused by a coronavirus or whether it is equally transmissible year-round. Depending on seasonality, the models show that social distancing occurring between 25 percent and 75 percent of the time would both build immunity and keep the health care system from overloading. As time passes and more of the population gains immunity, they said, the restrictive episodes could be shorter, with longer intervals between them.

Interventions such as development of a vaccine (12 to 18 months away at best), discovery of a treatment that lessens illness severity, or effective case identification and contact tracing would change the situation. They also modeled what would happen if the U.S. doubled the number of critical-care beds in the hospital system. That increase in capacity to handle the sickest patients would allow social distancing to end in early to mid-2021, with the epidemic here over in 2022. Absent any social distancing, the model predicts the epidemic would be over sometime this fall, but at the cost of an overwhelmed health care system and, presumably, many more deaths. After that, the virus would circulate periodically, similar to cold, flu and other regular contagions.

Grad acknowledged that he didnt know whether the political will existed for such an on-again, off-again treatment, but Sarah Fortune, chair of the Harvard Chan Schools Department of Immunology and Infectious Diseases, said the research presents what she thinks is the most realistic available strategy. Its unlikely, she said, that the U.S. will be able to drive the genie back into the bottle, as China seems to have, and, since fragile health-care systems cover large parts of the world, the virus will almost certainly have reservoirs from which to reinfect countries.

The limits of what we can achieve even locally, in terms of COVID control is set by the weakest health care systems globally, said Fortune, speaking on a media conference call Thursday morning.

The research, released this week as an academic preprint and awaiting peer review, came amid warnings that the U.S. health care system may not be robust enough to begin either once-and-for-all easing of social distancing or to start an on-again, off-again regimen. Ashish Jha, director of the Harvard Global Health Institute, said the U.S. health care system has a steeper hill to climb than it otherwise would after wasting two months of vital preparation time. He said very aggressive social distancing is needed now to give the system time to catch up to the virus current spread. He called for tripling testing, increasing production of protective equipment, and coordinating response nationally.

The limits of what we can achieve even locally, in terms of COVID control is set by the weakest health care systems globally.

Sarah Fortune

Jha said it seems clear the epicenter of the pandemic is shifting from Europe to the U.S. Current case numbers here are approaching those of Italy and will likely soon thereafter surpass Chinas. U.S. deaths have topped 1,000, while the pandemics economic toll was reflected in a record number of Americans more than 3 million filing for unemployment benefits last week.

As cases in New York continued to soar, Jha said he was also deeply concerned about the rapid growth of the epidemic in New Orleans. Federal leadership, he said, could encourage social distancing nationwide that will dampen the epidemic in places where its not yet severe. It could also, together with epidemic modeling, direct scarce resources like ventilators to locations seeing a surge in cases, moving the supply from hotspot to hotspot. He also called for a standard policy concerning what to do when faced with life-saving equipment shortages. Such guidelines would help clinicians faced with the awful choice of who should get access to the equipment and who should not.

This is how we get through this together. If every state and every community fights to maximize its own ventilators, were all going to be in trouble. But if we can work in a coordinated way, we can get through it much easier, said Jha, speaking during a webcast event sponsored by The Forum at Harvard T.H. Chan School of Public Health and PRIs The World. It has to ultimately be done by the federal government. This is why we have a federal government.

Once the peak passes here, Fortune said, nations with weak health-care infrastructure will still be in the crosshairs, and shes concerned that an uncontrolled epidemic in these countries will be catastrophic. India, for example, has reported just 700 cases but has done very little testing, she said.

I do fear, where the health-care system is very fragile, what comes next is the pandemic playing out in a really catastrophic way, Fortune said.

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How to prevent overwhelming hospitals and build immunity - Harvard Gazette

Zoonotic diseases: Why are infections from animals so dangerous to hu – Medical News Today

In the wake of the COVID-19 global pandemic, which started when the virus SARS-CoV-2 jumped from animals into humans, we ask an important question why are infections acquired from animals so dangerous to human health?

While it is not yet clear which animals were the source of the new coronavirus was it bats? Was it pangolins? Was it both? scientists are sure that SARS-CoV-2, the virus that causes COVID-19, originated from animals.

The numbers of confirmed COVID-19 cases across the world are staggering. According to Johns Hopkins University, more than 730,000 people have contracted the virus and 34,000 people have died.

But zoonotic diseases that is, diseases acquired from animals were affecting vast numbers of people across the world before COVID-19 took center stage.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

An international report from 2012, for example, informed that a total of 56 such diseases were responsible for 2.5 billion cases of illness and 2.7 million deaths across the globe each year. These illnesses included rabies, toxoplasmosis, Q fever, Dengue fever, avian influenza, Ebola, and anthrax.

Furthermore, respiratory, flu-like diseases acquired from animals wreaked havoc in the past century. The Spanish flu caused 50 million deaths in 1918, and the Hong Kong flu caused 700,000 deaths in 1968.

So, why are diseases that humans acquire from animals so dangerous? Part of it is due to our immune system. Part of it is natural selection. The specific animal that transmits the virus may also play a role.

Below, we explore some of these factors and how they intertwine.

One reason viruses from animals are so dangerous to humans is that people have no means to deal with them. Our immune system was never introduced to these novel viruses, so it doesnt know how to respond to the uninvited guest.

Researchers explain that most of the viruses that enter the human body are successfully destroyed by the immune system or pass through our gastrointestinal system. However, now and then, an animal virus manages to replicate within a human host.

The moment where the animal virus replicates within the body of the first human is crucial. At this critical point, the virus can mutate and evolve under the selective constraints of the human body for the first time, adapting and improving itself for replication in this new host.

As this occurs, the human immune system must retaliate. It needs to catch up with the virus evolution and create an immune response. The human body has never been confronted with this threat before, and therefore, has no pre-existing immunity in its arsenal so it must devise one fast.

But, this defense part of the adaptive immune system takes days or longer to activate. In the meantime, the virus may have already evolved to replicate faster or even escape the immune systems retaliation.

In other words, the animal virus and the human immune system have entered an arms race and like with any arms race, one of the two competitors could win, or both competitors could reach a stalemate.

Medical News Today spoke to Christopher Coleman, assistant professor of Infection Immunology at the University of Nottingham in the United Kingdom, about animal viruses, human hosts, and the role of evolution and natural selection.

[T]he general assumption, he explained, is that as viruses evolve to a host, they become less dangerous to that host (they want to ensure their own transmission so dont want to rapidly kill the host before they get a chance [to replicate]).

This is by no means [always] true, but a virus that adapts to humans might be less dangerous in the long term because the evolutionary arms race between virus and host has reached a sort of stalemate where neither is perfectly happy, but neither is killed off.

Christopher Coleman

Furthermore, a virus that fully adapts to an animal host may be completely harmless to humans, Coleman continued.

The scientist whose main research focuses on highly pathogenic human coronaviruses gave examples of aggressive animal viruses within the coronavirus family. These include the infectious bronchitis virus of chickens, feline infectious peritonitis virus in cats, or transmissible gastroenteritis virus, which is near 100% fatal in piglets.

None of these [viruses] are known to infect or cause any disease in humans, Coleman said.

On the other hand, a virus that evolves in animals but also has an ability to infect humans may be more deadly if and or when it infects humans.

This may be especially true when the animals immune systems are very different from those of humans, or when the animals have special defense mechanisms that humans lack.

For instance, the fact that very harmful viruses such as SARS, MERS, and Ebola have all originated in bats begs the question what do bats have that we dont?

How can bats fly around carrying viruses that, in some cases, are extremely deadly to humans (such as Ebola), but that do not seem to harm these creatures in the slightest?

A new study, led by Cara Brook, a postdoctoral Miller Fellow at the University of California Berkeley, asked this very question. The research shows how bats unique immune capabilities enable them to carry and maintain a high viral load without getting sick themselves.

[S]ome bats, explain Brook and colleagues in their paper, have an antiviral immune response called the interferon pathway perpetually switched on.

In most other mammals, having such a hyper-vigilant immune response would cause harmful inflammation. Bats, however, have adapted anti-inflammatory traits that protect them from such harm.

Cara Brook et al

This is all great news for bats, but what does it do for other mammals? Sadly, not much. The fact that bats have such good defenses means that the virus has all the encouragement it needs to replicate more quickly.

The bats unique immune capabilities eventually make the viruses stronger. It is like training with an outstanding competitor and getting stronger as a result.

Brook and her team carried out experiments using cell lines from two species of bats. The results showed that in both bat species, the strongest antiviral responses were countered by the virus spreading more quickly from cell to cell.

This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures, including humans, are not.

Cara Brook et al.

Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology, says Brook.

In the case of the new coronavirus, multiple theories are circulating about the specific animal that passed on SARS-CoV-2 to humans. Scientists have implicated pangolins or even snakes as possible carriers.

Pinning down specific mammals is vital because the animal can offer insights into the genetic structure of the virus and ways to tackle it. However, it is essential not to discount the possibility that the new coronavirus might have several animal sources.

Commenting on the theory that humans contracted SARS-CoV-2 from pangolins, Coleman said: Its as good a theory as any [] This, of course, does not mean that pangolins are the only source it may be that there are other species.

For example, with the original SARS-CoV, civet cats were the most famous species involved, but there were other small mammals infected. Also, although dromedary camels are the source of MERS-CoV, there is strong evidence that other camelids can also be infected.

Regardless of which animals specifically gave humans the new coronavirus, it may be more important to ask, when and where did the virus mutate?

In a recent study, researchers led by Kristian Andersen, Ph.D., an associate professor of immunology and microbiology at the Scripps Research Institute in LaJolla, CA, used the available genomic data to determine whether the origin of the new coronavirus was natural or made by humans.

Having determined that the virus is the result of natural evolution, the authors explain that depending on whether the virus adapted in its current form in animals or humans, the course of the new coronavirus pandemic could be quite different.

[I]f SARS-CoV-2 pre-adapted in another animal species, write the authors in the journal Nature, then there is the risk of future re-emergence events.

In other words, if the virus evolved to its current state in animals, then animals would continue to pass it amongst each other, and the virus could jump back into humans at any point.

Furthermore, the researchers suggest that this scenario would explain why the virus spread so quickly. Seeing that it had already developed its pathogenic traits in animals, SARS-CoV-2 was already trained to spread and replicate quickly once it entered its first human host.

In contrast, write Andersen and colleagues, if the adaptive process occurred in humans, then even if repeated [animal-to-human] transfers occur, they are unlikely to take off without the same series of mutations, therefore minimizing the chances of another outbreak.

For now, it is impossible to know which of the two scenarios is more likely. Only time, and more research, will tell.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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Zoonotic diseases: Why are infections from animals so dangerous to hu - Medical News Today

What Swiss researchers are doing to beat Covid-19 – swissinfo.ch

A colourisedscanning electron micrograph of a cell infected with SARS-COV-2 viruswhich causes the Covid-19 disease.

While Switzerland continues to be a hotspot for coronavirus cases, Swiss scientists and drug companies are playing an important role in the global effort to develop treatments or a vaccine for the virus.

The scientific community has responded much more effectively to the Covid-19 outbreak than to the SARS outbreak, Francesco Stellacci, professor at Lausannes Federal Institute of Technology (EPFL) said.

Stellacci has been working on developing a broad-spectrum anti-viral drug for the past 10 years. In an interview published by EPFLexternal link, he said data had been shared very quickly and everyone has helped each other out.

The scientific community truly grasped the importance of expanding the scope of research and sharing everything openly.

The collaboration appears to be bearing fruit. Only three months have gone by since Chinese health officials first informed the World Health Organization about a cluster of 41 patients with a mysterious pneumonia in Wuhan on December 31. Despite the short time frame, there is a lot of progress to report on the research side.

The Department of Immunology at the University Hospital in Bernhas been working on a vaccine since January. Initial sequences of the virus were quickly isolated. The vaccine has already been tested on animals.

Meanwhile,Peter Burkhard, an immunologist with a private laboratory in cantonBasel City, has alsodeveloped aprecursor of the Covid-19 vaccine, which has been tested on animals and he is now testing on himself. See the full report in this swissinfo.ch video .

There will soon be more research in the pipeline after the Swiss National Science Foundation (SNSF) put out an emergency call for proposals on research into coronaviruses on February 25 to tackle the current crisis and prepare for future likely epidemics. A sum of CHF5 million ($5.2 million) has been earmarked for projects.

The first call of its kind ever organised by the SNSF received 220 applications. The majority of projects were biomedical, including studies of viruses and infections, the immune response in humans and the spread of the disease.

The selected projects will provide a basis for the subsequent industrial development of active agents. The grants available are between CHF50,000 and CHF300,000 per project.

The best defence against this virus is a vaccine, but since it is likely to take at least 18 months to develop one, a broad-spectrum anti-viral drug could buy us some time, according to Franceso Stellaccio.

While a miracle cure is still the dream of all those working hard in the lab, Stellaccio explains that a less effective drug would also be beneficial to society.

Current data show that every person who catches the virus infects 2.6 other people on average. So a drug with an efficacy of 50% would reduce this figure to 1.3, and that would slow the viruss spread considerably.

It is often the case that a drug developed for one condition can turn out to be useful for other indications. In a promising development, Relief Therapeutics, headquartered in Zurich, is making progress with its erectile dysfunction drug Aviptadil, which has been found to be helpful in treating patients with Acute Respiratory Distress Sydrome (ARDS).

With the coronavirus, death is primarily caused by ARDS, in which severe inflammation causes the lungs to fill with fluid. Aviptadil is a patented formulation of Vasoactive Intestinal Polypeptide (VIP), a naturally occurring peptide hormone that is concentrated in the lungs.

Relief Therapeutics announced on March 26external link that it has filed an investigational new drug application with the US Food and Drug Administration (FDA), in collaboration with an American drug development company, NeuroRx. The application is for a phase two trial of Aviptadil in the treatment of acute and moderate respiratory distress in patients infected by the coronavirus.

Also in the last week, Swiss pharmaceutical giant Roche announced it was launching a clinical trial of a potential new Covid-19 drug, another case of repurposing. Roche is working with the FDA and the US government to initiate a phase three trial to evaluate the safety of Actemra, a drug used to treat two inflammatory diseases. The drug is known as RoActemra outside the US. As reported on March 20, the study will enrol about 330 patients globally starting next month, including in the US. Actemra works by inhibiting the bodys immune response.

Meanwhile, a number of Swiss university hospitals in Zurich, Lausanne, Geneva and St Gallen are preparing to carry out serological tests to detect the presence of Covid-19 antibodies in the blood.

The aim is to estimate the proportion of the population that is already immune to the disease. The higher the proportion, the better the protection against a second wave of infections.

"Today we know that we have a certain number of infected people but we dont have the exact denominator, because only symptomatic people are being tested. It would be useful to have those numbers to better manage the crisis as a whole, Gilbert Greub, senior physician at the Institute of Microbiology in Lausanne University Hospital told Swiss public television RTS.

Although many different avenues are being pursued simultaneously, there will be no quick fix to the immediate problem through a drug or vaccine. Professor Stellacci stressed the importance of managing the expectations of the public in this stressful time.

We have to be clearer about what were doing, the challenges we face and the time it will take. Otherwise we may be selling false hope.

Switzerland is oneof the countries most affected by the coronavirus, with almost 16,000 positive tests and more than 350 deaths.

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Meet the Black Female Scientist Paving the Way In Race to Develop COVID-19 Vaccine – Atlanta Black Star

Dozens of researchers around the world are racing to create a vaccine to eliminate the COVID-19 pandemic. Dr. Kizzmekia S. Corbett, a viral immunologist working with the National Institute of Allergy and Infectious Diseases, is a front-runner in its development.

Corbett is a lead researcher with Dr. Barney Grahams coronavirus team in the Vaccine Research Center in the NIAID, which is part of the National Institutes of Health. (The NIH, an agency within the Department of Health and Human Services, is the federal governments main biomedical research organization.)

Corbetts team has been working in recent weeks to help test and develop An experimental vaccine invented by private biotech company Moderna Inc. Along the way, her teams role was to grow so-called spike protein, a key component of Modernas coronavirus vaccine. (The NIH describes the spikes and virus thusly: Coronaviruses are spherical and have spikes protruding from their surface, giving the particles a crown-like appearance. The spike binds to human cells, allowing the virus to gain entry.)

Years of research into similar viruses had given Corbetts Vaccine Research Center team valuable experience at growing this protein, which they did quickly and sent to Moderna. With they received the first research doses of vaccine from Moderna, Corbett and her fellow scientists immunized dozens of mice. Days later, blood samples that were collected from the mice where checked to see if the mice were producing antibodies against that all-important spike protein.

When her team sent word of the positive results, it was absolutely amazing, Corbett told The Associated Press earlier this month.

The work, which cleared the way for a new phase 1 clinical trial on March 3, couldnt have moved so quickly had it not been for years of behind-the-scenes lab testing of a possible MERS vaccine, Corbett added.

I think about it a lot, how many of the little experimental questions we did not have to belabor this time around, Corbett said. As she saw the first promising mouse tests, she told AP, I felt like there was a beginning of all of this coming full circle.

Corbett had told Dr. Anthony S. Fauci, the NIAID director, it would take about 100 days to move into the trial. The group did it in 66.

Although an actual vaccine wont be ready for another 12 to 18 months, the announcement marks a new record in moving to human testing, Bloomberg reports. The NIH fellow started her work in January, when researchers first learned how infectious and contagious the virus is and how easily it spreads.

Corbett has nearly 10 years of research experience in immunology.

She received a B.S. in biological sciences, with a secondary major in sociology, from the University of Maryland-Baltimore County in 2008. After one year of post-baccalaureate training at NIH, she enrolled at University of North Carolina, from where she obtained her Ph.D. in microbiology and immunology in 2014.

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Meet the Black Female Scientist Paving the Way In Race to Develop COVID-19 Vaccine - Atlanta Black Star

Unlocking the Secrets of Brown Fat – Michigan Medicine

In recent years, brown fat has garnered attention as the so-called good fat that can protect against obesity and its associated health risks, like cardiovascular disease and diabetes. Two separate major studies, one led by Liangyou Rui, Ph.D. and one by Ling Qi, Ph.D., both with the department of molecular & integrative physiology, help explain brown fats properties.

Located in small pockets throughout the body, most mammals use brown fat (and its closely related cousin beige fat) to stay warm. In mice and humans, if you have more brown or beige fat, you are more protected from metabolic disease, says Rui, the Louis G. D'Alecy Collegiate Professor of physiology at U-M Medical School, whose lab studies the molecular and physiological mechanisms of obesity, diabetes and fatty liver disease. In a new study published in Nature Communications, Rui, first author Lin Jiang, Ph.D., and their colleagues reveal a pathway by which the hormone leptin contributes to weight loss.

Leptin regulates body weight by controlling appetite and energy expenditure, but exactly how has been a mystery. What is known, says Rui, is that leptin activates brown and beige fat. The new study elucidates a molecular accelerator of leptin action in the brain called Sh2b1. His team has found that Sh2b1 in the hypothalamus, an important brain region controlling body temperature and hunger among other functions, promotes the stimulation of the sympathetic nervous system. The sympathetic nervous system sends signals to brown and beige fat to activate it, thus maintaining body weight and metabolism.

The team demonstrated this proof-of-principle by creating two mouse models. Mice that lacked the Sh2b1 gene in the leptin receptor neurons had an incredibly reduced sympathetic drive to the brown and beige fat and reduced capability to promote energy expenditure, says Rui. This reduced the ability of brown fat to be metabolized into heat, lowering the mices core body temperature. Whats more, the mice also developed obesity, insulin resistance and a fatty liver. In contrast, mice with extra expression of Sh2b1 in their brains were protected from obesity.

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No one knew that Sh2b1 in the brain controls the sympathetic nervous system or was required for leptin to activate brown fat to increase energy expenditure, notes Rui. As for how this finding could be applied to humans, he says the hope is to eventually find a way to increase expression of Sh2b1 or its ability to enhance leptin signaling and fat burning.

Other U-M authors contributing to this paper include: Haoran Su, Xiaoyin Wu, Hong Shen, Min-Hyun Kim, Yuan Li, Martin G. Myers Jr, and Chung Owyang.

Brown fat gets its color from high amounts of iron-containing mitochondria, unlike the standard white fat linked to obesity. A team led by Qi, a professor of molecular & integrative physiology and internal medicine at U-M Medical School has been studying how mitochondria, the power plant of the cell, and another cellular structure called the endoplasmic reticulum (ER), which is involved in the production of proteins and lipids, interact inside brown fat cells.

In particular, theyve studied the role of a protein complex involved in a process called ER-associated protein degradation, or ERAD. Simply put, ERAD is the process of removing and destroying misfolded proteins, like taking out the trash out of the ER.

Everyone thought that ERAD was just part of the general cellular response when cells are undergoing ER stress, says Qi. Weve shown over the past six years that it plays a fundamental role in health and disease.

In a new study, published in Science, Qi along with first authors Zhangsen Zhou, Ph.D., Mauricio Torres, Ph.D., and their colleagues demonstrate how an ERAD protein complex affects the proper function of mitochondria.

Typically, the ER and mitochondria have ongoing interaction at touch points called mitochondria-associated membranes. These points of contact mark areas for mitochondria to divide for the production of new mitochondria and for the exchange of other molecules such as lipids and calcium. The ER forms tubules that surround the mitochondria to get them ready for division.

Using state of the art 3D imaging, the researchers discovered what happens to mitochondria in brown fat that are missing part of an ERAD protein complex, called Sel1L-Hrd1, when exposed to cold.

When you delete this complex in brown adipocytes, the mitochondria become elongated and enlarged, says Qi. The 3D image enabled them to view a previously unrecognized interaction between the mitochondria and the ER, with the mitochondria wrapping in a U-shape around the ER tubules.

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When the mice were placed in a cold environment, the ends of the outer membrane of the mitochondria folded back on itself, eventually fusing and completely enveloping the ER tubules. The result, says Qi, are abnormally large, misshapen, dysfunctional mitochondria.

We showed that these mitochondria dont function normally and the mice become cold sensitive, their body temperature dropping very quickly, says Qi. In other words, without this ERAD protein complex, the brown fat is not being used to generate heat. Under a microscope, this dysfunctional brown fat had larger droplets of lipids than brown fat from mice with the protein complex intact.

This is highly unexpected. The results here fundamentally change our understanding of ER-mitochondrial communication and further demonstrate the importance of an ER degradation complex in cell biology.

This paper also includes contributions from the following U-M authors: Christopher Halbrook, Franoise Van den Bergh, Rachel B. Reinert, Siwen Wang, Yingying Luo, Allen H. Hunter, Thomas H. Sanderson, Aaron Taylor, Costas A. Lyssiotis, Jun Wu and Daniel A. Beard.

Papers cited:

Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease, Nature Communications, DOI: 10.1038/s41467-020-15328-3

Endoplasmic reticulumassociated degradation regulates mitochondrial dynamics in brown adipocytes, Science, DOI: 10.1126/science.aay2494

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Unlocking the Secrets of Brown Fat - Michigan Medicine

What does it take to receive a National Science Foundation CAREER award? – Nevada Today

The National Science Foundations Faculty Early Career Development (CAREER) Program sets the bar high. It is the NSFs most prestigious award in support of early-career faculty, described by the NSF as supporting those with the potential to serve as academic role models in research and education and to lead advances in the mission of their department or organization.

Feifei Fan, assistant professor in the College of Engineering; Heather Holmes, assistant professor in the College of Science; and Robert Renden, assistant professor in the School of Medicine are the latest University of Nevada, Reno faculty to receive CAREER awards, bringing the total number of University faculty to receive the award since 2013 to 20.

Holmes wildfire-smoke research through the Department of Physics Atmospheric Sciences Program has received support from NASA, NSF and NIH and has resulted in epidemiological advancements. Her CAREER proposal, supported by a $400,000 grant, seeks to improve forecasting of wildfire smoke by improving atmospheric modeling, especially for summer atmospheric mixing over mountainous areas.

Fans research through the Department of Mechanical Engineering is set against the backdrop of the growing and critical importance of rechargeable batteries. Her CAREER proposal, supported by a $500,000 grant, focuses on the complex electrochemical cycling of batteries and, through study of the mechanics and other physical and chemical processes in electrodes, seeks to improve energy density, power density and capacity retention.

Rendens neurological research through UNR Meds Department of Physiology and Cell Biology and the Universitys Neuroscience Institute explores how brain cells maintain the energy needed to communicate at contact sites, called synapses. The prevailing view is that mitochondria supply this energy, but Rendens research data suggests other mechanisms are at play. Understanding this will inform experiments to correct systems where mitochondrial function is impaired, such as in neurodegenerative disease and aging. A $1.1 million CAREER grant will support his work.

The CAREER proposals of Holmes, Fan and Renden are in line with advice that Jamie Voyles-Ensor, associate professor of biology and 2019 CAREER awardee, received from an NSF program manager and shared during a February 2020 panel session sponsored by Research & Innovation. It should be something that can be accomplished, yet is a stretch, Voyles-Ensor said Its a tricky line to define.

More than 30 faculty members gathered for the panel session, indicating growing campus interest in the CAREER program and awards. Joining Voyles-Ensor as panelists were 2019 CAREER awardees Matteo Aureli, associate professor of mechanical engineering, and Mohammed Ben-Idris, assistant professor electrical and biomedical engineering.

Aureli shared that he held off applying until he was at a place in his career where he was more confident of his research interest and had a body of work to substantiate it. As he said, Its about your career. You need to show a line that is different from the work of your mentor.

It has to be new, advised Ben-Idris. Come up with a unique research approach. Make the case in the first two pages.

Describe the work in a way that is widely understandable one that your grandmother will understand before describing it in a scientific way that your science colleagues will understand, said Voyles-Ensor. Your proposal will be reviewed by scientists, but from a range of fields and not necessarily familiar with your field.

Aureli also encouraged developing a thorough, thought-out budget. It shows you are serious and committed. It helped me get more specific and dialed in about the scope of my project, he said.

In addition to the panel session, efforts by Research & Innovation to encourage and support faculty to prepare for the CAREER award application process include proposal writing workshops, a suggested timeline and the opportunity for external review. In the months of April and May, potential applicants are encouraged to draft their full-project summary for external-review. By June 1, contact your colleges grant coordinator or, if your college doesnt have a grant coordinator, contact Proposal Capture Manager Carrie Busha or Proposal Editor Kate Dunkelberger to develop a personalized timeline for submission.

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What does it take to receive a National Science Foundation CAREER award? - Nevada Today