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Scientists Discover How Oral Secretions of Insect Pest Trigger Innate Defense Responses in Plants; Unprecedented Findings Represent Massive Step Forward Toward Developing Strategies for Pest Control In Crop Plants

In nature, every species must be equipped with a strategy to be able to survive in response to danger. Plants, too, have innate systems that are triggered in response to a particular threat, such as insects feeding on them. For example, some plants sense "herbivore-derived danger signals" (HDS), which are specific chemicals in oral secretions of insects. This activates a cascade of events in the plant's defense machinery, which leads to the plant developing "resistance" to (or "immunity" against) the predator. But despite decades of research, exactly how plants recognize these signals has remained a bit of a mystery. In a new study published in Communications Biology (https://www.nature.com/articles/s42003-020-0959-4), a research team from Tokyo University of Science, Ehime University, Okayama University, The University of Tokyo, and Iwate Biotechnology Research Center, led by Professor Gen-ichiro Arimura, PhD, attempts to shed light on exactly how plant HDS systems work. They chose to study membrane proteins called "receptor-like kinases" (RLKs), which are found in soybean leaves. They based their study on previous evidence from plants like Arabidopsis, tobacco, and cowpea, in which RLKs play a major role in HDS systems. Their results published online on May 8, 2020 in Communications Biology. The open-access article is titled” Soy and Arabidopsis receptor-like kinases respond to polysaccharide signals from Spodoptera species and mediate herbivore resistance.” Professor Arimura says, "Scientists have been trying to understand the molecular mechanism of plant resistance for years, but the 'sensors' involved in plant recognition of insect pests are still not known.

New Study Shines Light on Mysterious Giant Viruses

In recent years, giant viruses have been unearthed in several of the world's most mysterious locations, from the thawing permafrost of Siberia to locations unknown beneath the Antarctic ice. In a new study, a team of Michigan State University (MSU) scientists shed light on these enigmatic, yet captivating, giant microbes and key aspects of the process by which they infect cells. The study results were published online on May 8, 2020 in Cell. The article is titled "Structural and Proteomic Characterization of the Initiation of Giant Virus Infections." With the help of cutting-edge imaging technologies, this study developed a reliable model for studying giant viruses and is the first to identify and characterize several key proteins responsible for orchestrating infection. Giant viruses are bigger than 300 nanometers in diameter and can survive for many millennia. For comparison, the rhinovirus -- responsible for the common cold -- is roughly 30 nanometers in diameter. "Giant viruses are gargantuan in size and complexity," said principal investigator Kristin Parent, PhD, Associate Professor of Biochemistry and Molecular Biology at MSU. "The giant viruses recently discovered in Siberia retained the ability to infect after 30,000 years in permafrost." The outer shells -- or capsids -- are rugged and able to withstand harsh environments, protecting the viral genome inside. The capsids of the species analyzed in this study -- mimivirus, Antarctica virus, Samba virus, and the newly discovered Tupan viruses -- are icosahedral, or shaped like a twenty-sided die. These species have a unique mechanism for releasing their viral genome. A starfish-shaped seal sits atop one of the outer shell vertices.

Newly Discovered Dendritic Cell Plays Crucial Role in Immune Response to Respiratory Infections

With a discovery that could prompt a rewrite of immunology textbooks, an international group of scientists, including the research teams of Bart Lambrecht, PhD; Martin Guilliams, PhD; Hamida Hammad, PhD; and Charlotte Scott, PhD (all from the VIB-UGent Center for Inflammation Research) identified a new type of antigen-presenting immune cell. These cells, which are part of an expanding family of dendritic cells, play a crucial role in presenting antigens to other immune cells during respiratory virus infections, and could explain how convalescent plasma helps to boost immune responses in virus-infected patients. When our body faces an infection, it responds with inflammation and fever. This is a sign that the immune system is doing its work, and leads to the activation of many cells, like soldiers in an army. Dendritic cells (DCs) are the generals of that army. They can precisely activate and instruct the soldiers to kill infected cells by presenting antigens derived from the “invaders” to cells of the immune system. There are several types of DCs that perform antigen-presenting functions in the body. A first type of conventional DCs continuously scans the body for dangerous invaders, even when there is no infection. When there is inflammation triggered by infection, another subset of DCs emerges from inflammatory monocytes. Because monocyte-derived DCs are easily prepared in vitro from monocytes isolated form human blood, it was always assumed these cells were very important antigen-presenting cells. Clinical trials using monocyte-derived DCs in cancer therapy have, however, been disappointing.

AstraZeneca & Oxford University Announce Landmark Agreement for COVID-19 Vaccine (Weakened Adenovirus Containing mRNA for Viral Spike Protein); Collaboration Will Enable Global Development, Manufacturing, and Distribution of Vaccine

On April 30, 2020, AstraZeneca and the University of Oxford announced an agreement for the global development and distribution of the University’s potential recombinant adenovirus vaccine aimed at preventing COVID-19 infection from SARS-CoV-2. The collaboration aims to bring to patients the potential vaccine known as ChAdOx1 nCoV-19, being developed by the Jenner Institute and Oxford Vaccine Group, at the University of Oxford. Under the agreement, AstraZeneca would be responsible for development and worldwide manufacturing and distribution of the vaccine. Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “As COVID-19 continues its grip on the world, the need for a vaccine to defeat the virus is urgent. This collaboration brings together the University of Oxford’s world-class expertise in vaccinology and AstraZeneca’s global development, manufacturing, and distribution capabilities. Our hope is that, by joining forces, we can accelerate the globalization of a vaccine to combat the virus and protect people from the deadliest pandemic in a generation.” Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “The University of Oxford and AstraZeneca have a longstanding relationship to advance basic research and we are hugely excited to be working with them on advancing a vaccine to prevent COVID-19 around the world. We are looking forward to working with the University of Oxford and innovative companies such as Vaccitech (https://www.vaccitech.co.uk/), as part of our new partnership.” Alok Sharma, UK Business Secretary, said: “This collaboration between Oxford University and AstraZeneca is a vital step that could help rapidly advance the manufacture of a coronavirus vaccine.

New Vaccine Platform Applicable to Various Viruses; Includes RNA As Immunostimulatory Agent (Adjuvant) and Compounds to Maintain Stability of RNA; Platform with Spike Protein Antigen Confers Immunity When Tested Against MERS in Mice

Middle East Respiratory Syndrome (MERS), which struck South Korea in a 2015 outbreak, was caused by a coronavirus--the same family of viruses that is responsible for COVID-19 (disease: COVID-19, virus: SARS-CoV2). Recently, a Korean research team announced that it had developed a new vaccine platform using RNA-based adjuvants for the MERS coronavirus (MERS-CoV). The research team successfully conducted an experiment on non-human primates. It is expected that the new vaccine platform will soon be applicable to the development of a COVID-19 vaccine, an urgent global health priority. The Korea Institute of Science and Technology (KIST) (https://www.nst.re.kr/nst_en/member/03_02.jsp) recently released the results of the joint research on the RNA-based vaccine platform for MERS-CoV, conducted by a research team led by Dr. Keum Gyo-chang and Dr. Bang Eun-kyoung from the KIST's Center for Neuro-Medicine and a research team led by Professor Nam Jae-Hwan from the Catholic University of Korea (CUK). The vaccine platform uses RNA as an immunostimulatory agent known as an adjuvant and consists also of compounds that maintain the stability of the RNA, together with the spike protein that the virus uses to invade the host cell. The new vaccine platform is expected to be used in the development of a vaccine for the COVID-19 virus, which is also a type of coronavirus. Recently, many protein-based vaccines have been developed as they are regarded as having a high level of safety. However, protein-based vaccines induce a weak immune response in antibody-producing cells. This requires the use of a highly stable adjuvant for a more balanced immune response.

Novant Health Initiates Phase 2b/3 Trial with CytoDyn’s Leronlimab for Severely and Critically Ill COVID-19 Patients; FDA Has Approved 54 Emergency INDs to Allow Access to Leronlimab for Severely & Critically Ill COVID-19 Patients

On May 7, 2020, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced that Novant Health (link) is initiating patient enrollment in CytoDyn’s Phase 2b/3 trial for severely and critically ill COVID-19patients. Leronlimab has been administered to 54 severely and critically ill COVID-19 patients thus far under Emergency Investigational New Drug (EINDs) authorizations granted by the FDA. Preliminary results from this patient population led to the FDA’s recent clearance for CytoDyn’s Phase 2b/3 clinical trial for 390 patients, which is a randomized, placebo-controlled trial with a 2:1 ratio of active drug to placebo ratio. Patients enrolled in this trial are expected to be administered leronlimab for two weeks with the primary endpoint being the mortality rate at 28 days, and a secondary endpoint of mortality rate at 14 days. The Company will perform an interim analysis on the data from 50 patients. “We’re grateful for our partnership with CytoDyn and the opportunity to bring cutting-edge, innovative and investigative treatments to our community,” said Eric Eskioglu, MD, Executive Vice President and Chief Medical Officer for Novant Health. “Since initiating the leronlimab mild/moderate last month, Novant Health has screened nearly 400 patients for eligibility. A number of these patients have been enrolled and treated on the mild/moderate clinical trial. Expanding treatment options for our more critically ill patients is a vital step in our fight against COVID-19.

Moderna Announces FDA Clearance for Phase 2 Study of mRNA Vaccine (mRNA-1273) for COVID-19; Company Awarded Up to $483 Million from BARDA for Accelerated Development of mRNA-1273; Lonza to Manufacture Up to One Billion Doses of mRNA-1273 Per Year

On May 7, 2020, Cambridge, MA-based Moderna, Inc. (Nasdaq: MRNA), a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today reported financial results and provided business updates for the first quarter of 2020 and highlighted pipeline progress. The company also announced FDA approval of the company progressing to a Phase 2 trial for its mRNA vaccine (mRNA-1273) for COVID-19. Moderna is conducting clinical trials of this vaccine in collaboration with the National Institute of Allergy and Infectious Diseaes (NIAID), headed by Dr. Anthony Fauci. “The imminent Phase 2 study start is a crucial step forward as we continue to advance the clinical development of mRNA-1273, our vaccine candidate against SARS-CoV-2. With the goal of starting the mRNA-1273 pivotal Phase 3 study early this summer, Moderna is now preparing to potentially have its first BLA approved as soon as 2021. We are accelerating manufacturing scale-up and our partnership with Lonza puts us in a position to make and distribute as many vaccine doses of mRNA-1273 as possible, should it prove to be safe and effective,” said Stéphane Bancel, Moderna’s Chief Executive Officer. “We also are continuing to progress our development pipeline and invest in our future. We are very pleased with Vertex’s decision, based on our preclinical progress, to extend our strategic collaboration working to develop the technology to allow for delivery of mRNA in the lung.” NEW UPDATES AND RECENT PROGRESS: Infectious Diseases-- The U.S.

Bat “Super Immunity” May Explain How Bats Can Carry Coronaviruses with No Apparent Harm, Saskatchewan Study Suggests; Effects of Stress on Delicate Balance of Bat-Virus Mutual Adaptation May Underlie Virus Jumps to Humans & Other Species

A University of Saskatchewan (USask) research team has uncovered how bats can carry the Middle East respiratory syndrome (MERS) coronavirus without getting sick--research that could shed light on how coronaviruses make the jump to humans and other animals. Coronaviruses such as MERS, Severe Acute Respiratory Syndrome (SARS), and more recently the COVID19-causing SARS-CoV-2 virus, are thought to have originated in bats. While these viruses can cause serious, and often fatal, disease in people, for reasons not previously well understood, bats seem unharmed. "The bats don't get rid of the virus and yet don't get sick. We wanted to understand why the MERS virus doesn't shut down the bat immune responses as it does in humans," said USask microbiologist Vikram Misra, PhD. In research just published in Scientific Reports, the team has demonstrated, for the first time, that cells from an insect-eating brown bat can be persistently infected with MERS coronavirus for months, due to important adaptations from both the bat and the virus working together. The open-access article is titled “Selection of Viral Variants During Persistent Infection of Insectivorous Bat Cells with Middle east Respiratory Syndrome Coronavirus.” "Instead of killing bat cells as the virus does with human cells, the MERS coronavirus enters a long-term relationship with the host, maintained by the bat's unique 'super' immune system," said Dr. Misra, corresponding author on the paper. "SARS-CoV-2 is thought to operate in the same way." Dr. Misra says the team's work suggests that stresses on bats--such as wet markets, other diseases, and possibly habitat loss--may have a role in coronavirus spilling over to other species.

Most Critically Ill COVID-19 Patients Survive with Standard Treatment; MGH & BIDMC Clinicians Urge Evidence-Based ARDS Treatments for COVID-19 Patients; Docs Should Await Standardized Clinical Trials Before Contemplating Novel Therapies

Clinicians from two hospitals in Boston report that the majority of even the sickest patients with COVID-19--those who require ventilators in intensive care units--get better when they receive existing guideline-supported treatment for respiratory failure. The clinicians, who are from Massachusetts General Hospital (MGH) and Beth Israel Deaconess Medical Center, published their findings in the American Journal of Respiratory and Critical Care Medicine. The open-access article was published online on April 29,2020 and is titled “Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study.” During the COVID-19 pandemic, hospitals around the world have shared anecdotal experiences to help inform the care of affected patients, but such anecdotes do not always reveal the best treatment strategies, and they can even lead to harm. To provide more reliable information, a team led by C. Corey Hardin, MD, PhD, an Assistant Professor of Medicine at MGH and Harvard Medical School, carefully examined the records of 66 critically ill patients with COVID-19 who experienced respiratory failure and were put on ventilators, making note of their responses to the care they received. The investigators found that the most severe cases of COVID-19 result in a syndrome called Acute Respiratory Distress Syndrome (ARDS), a life-threatening lung condition that can be caused by a wide range of pathogens. "The good news is we have been studying ARDS for over 50 years and we have a number of effective evidenced-based therapies with which to treat it," said Dr. Hardin. "We applied these treatments--such as prone ventilation where patients are turned onto their stomachs--to patients in our study and they responded to them as we would expect patients with ARDS to respond.

Four-Amino-Acid Region in Loop of COVID-19 Spike Protein Structure May Be Clue to High Infection Rate

Cornell University researchers, with a collaborator from the Université Paris-Saclay, INRAE, UVSQ, Virologie et Immunologie Moléculaires, have been studying the structure of the virus that causes COVID-19, and found a unique feature that might explain why it is so transmissible between people. Researchers also note that--aside from primates--cats, ferrets, and mink are the animal species apparently most susceptible to the human virus. Gary Whittaker, PhD, Professor of Virology, is the senior author on the study, which identifies a structural loop in the SARS-CoV-2 spike protein, the area of the virus that facilitates entry into a cell, and a sequence of four amino acids in this loop that is different from other known human coronaviruses in this viral lineage. An analysis of the lineage of SARS-CoV-2 showed it shared properties of the closely related SARS-CoV-1, which first appeared in humans in 2003 and is lethal but not highly contagious, and HCoV-HKU1, a highly transmissible but relatively benign human coronavirus. SARS-CoV-2 is both highly transmissible and sometimes lethal. "It's got this strange combination of both properties," Dr. Whittaker said. "The prediction is that the loop is very important to transmissibility or stability, or both." Dr. Whittaker said the researchers are focused on further study of this structural loop and the sequence of four amino acids. Cats, ferrets, and minks are also susceptible. In order to infect a cell, features of the spike protein must bind with a receptor on the host cell's surface, and cats have a receptor binding site that closely matches that of humans. To date, infections in cats appear to be mild and infrequent, and there is no evidence that cats can, in turn, infect humans. Dr.

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