Bio-IT Industry Continuing To Gain Insight On COVID-19, And Other News

May 15, 2020 | A genome in pangolins could reveal a treatment option for COVID-19. A lack amount MicroRNA may explain why older individuals and those with preexisting medical conditions are vulnerable for contracting the virus. We round up the week’s research and industry news for COVID-19.

Literature Updates |

The genome of pangolins could point to possible treatment options for COVID-19 in humans, according to researchers at the Medical University of Vienna. Their study, published in Frontiers in Immunology, finds that the exotic animal (resembling an anteater) lacks two of the virus-sensing genes that trigger an immune response in most mammals. The finding is significant because pangolins can be carriers of coronavirus, but they appear to tolerate it through some other unknown mechanism. Researchers focused on pangolins they are suspected of transmitting the virus to humans last year, creating the interspecies jump required for the current pandemic to take hold. They suggest that pharmaceutical suppression of gene signaling could be a possible treatment option for severe cases of COVID-19. DOI: 10.3389/fimmu.2020.00939

Korean research team has announced that it has developed a new vaccine platform using RNA-based adjuvants (immunostimulatory agents) for the MERS coronavirus (MERS-CoV). As reported in Angewandte Chemie, researchers conducted an experiment on nonhuman primates using a mixture of RNA of the cricket paralysis virus, an RNA stabilizer containing zinc complex, and the spike protein of the MERS-CoV. After just one inoculation, the vaccine was shown to have 100% protective efficacy against lethal doses of the virus; MERS-CoV infection was also suppressed through the induction of high neutralizing antibodies when the same vaccine was administered to macaque monkeys. Many protein-based vaccines are underdevelopment, but they induce a weak immune response in antibody-producing cells that highly stable adjuvants can address. Researchers say the platform will soon be applicable to the development of a COVID-19 vaccine, which is caused by the same type of virus, and they have formed a consortium with SK Bioscience to that end. DOI: 10.1002/anie.202002979

Controlling the body's inflammatory response to SARS-CoV-2 will likely be as important as antiviral therapies or a potential vaccine, according to a research brief appearing in Cancer & Metastasis Reviews. Rather than blocking cytokines, medical staff could turn off virus-induced inflammation by broadly activating the body's natural inflammation-clearing activities. Lipid mediators derived from omega-3 fatty acids serve as the body's natural "stop" signals to inflammation and increasing their levels could be a new therapeutic approach to preventing life-threatening inflammation caused by SARS-CoV-2. Such compounds are already in clinical trials for other inflammation-driven diseases, such as eye disease, periodontal disease and pain. DOI: 10.1007/s10555-020-09889-4

Researchers at Baylor College of Medicine and Texas Children's Hospital say designing a vaccine for COVID-19 has its unique challenges and requires an understanding of how the immune system naturally responds to a specific infection as well as how vaccines might trigger specific protective responses, as they discuss in a pair of papers published in Microbes and Infection and Nature Reviews Immunology. Evidence supports the likelihood that immunizing against the virus spike protein's receptor binding domain represents a realistic and viable vaccination strategy. In collaboration with the New York Blood Center, the researchers are developing a vaccine strategy based on this fragment of the viral protein. Prior attempts to develop vaccines against respiratory viruses suggest that some formulations may trigger undesirable responses, some cell-mediated and others as a result of “antibody-dependent enhancement” as has been previously observed in dengue. The receptor binding domain of the virus excludes sections of viral proteins that might potentially induce antibody-dependent enhancement. Experimental evidence suggests their vaccine leads to neutralization of the virus; in preclinical studies it was able to trigger an immune response that is protective and didn’t induce undesirable cellular immune responses. DOI: 10.1038/s41577-020-0323-4

Researchers at the Luxembourg Centre for Systems Biomedicine (LCSB) at the University of Luxembourg are coordinating an international collaboration to build a COVID-19 Disease Map to serve as a repository of all current knowledge on the virus-host interaction mechanisms to support research and improve understanding of the disease. They describe the project and call for contributions from the R&D community worldwide in an article published in Nature Scientific Data. Currently, the collaborative effort has 162 participants from 25 countries. The disease map will provide a graphical, interactive representation of the disease mechanisms and a computational resource for analyses and disease modelling. Researchers are relying on a distributed, multi-tool, multi-group approach dictated by emergency time-constraints of the ongoing pandemic. They are also seeking looking for practicing physicians, clinicians and domain experts to help review the content and scope of the map to improve its quality and applicability. DOI: 10.1038/s41597-020-0477-8

Scientists in China have identified a pair of neutralizing antibodies, isolated from a patient who recovered from COVID-19, which bind to the glycoprotein spike of the SARS-CoV-2 virus and block its ability to bind to the human ACE2 receptor and mediate viral entry into host cells. Preliminary tests in a mouse model resulted in a reduction of virus titers, suggesting the antibodies (names B38 and H4) may offer therapeutic benefits in addition to informing the design of small molecule therapeutics and vaccine candidates to fight COVID-19. Each antibody binds simultaneously to different epitopes on the spike's receptor binding domain (RBD) and together may confer a stronger neutralizing effect than either antibody on its own—a prediction supported by in vitro experiments. Imaging confirmed that B38 binds to a subset of the amino acids bound by ACE2 in the RBD, explaining the strength of its neutralizing effects. DOI: 10.1126/science.abc2241

MicroRNA that should attack the virus causing COVID-19 when it tries to infect the body are diminished with age and chronic health problems, which may help explain why older individuals and those with preexisting medical conditions are vulnerable populations, investigators report in Aging and Disease. The researchers, from Augusta University and the University of Florida, say their long-term goal is to identify the biggest hitters and replenish those troops. In the current study, they looked at the RNA sequences of SARS, SARS-CoV-2 and the microRNAs that appeared to be attacking the virus, then used computer simulation to figure out which would logically fit together like puzzle pieces. The perusal included four samples of SARS and 29 samples of SARS-CoV-2, taken between January and April 2020 from individuals in 17 countries. MicroRNAs most proficient at attacking SARS-CoV-2 showed more than 10 target sites and might ultimately be found to be the most proficient at fighting the virus. MicroRNAs targeting SARS-CoV-2 were also associated with more than 72 biological processes, many known to become dysregulated and/or diminish in number with age and with underlying medical conditions like diabetes and cardiovascular disease. Nineteen of the 29 SARS-CoV-2 samples had identical microRNAs, indicating the virus has a uniform presence internationally and that any effective treatments or vaccines should have broad impact. DOI: 10.14336/AD.2020.0428

Scientists in the U.S. and Japan report that in the laboratory, cats can readily become infected with SARS-CoV-2 and may be able to pass the virus to other cats. The study, published in the New England Journal of Medicine, involved three cats administered SARS-CoV-2 isolated from a human patient. Within three days, the virus was detectable in all three cats. Another cat that hadn’t been administered the virus was also put in each of the three cages and, within six days, all the cats were infected. The virus was detectable via nasal swab but not rectally. The virus was not lethal and none of the cats showed signs of illness; all the animals cleared the virus after six days. Researchers say people quarantined in their house could pass COVID-19 to their animals as well as their children and spouse. They advise those with symptoms to avoid contact with cats and cat owners to keep their pet indoors. People are much less likely to get COVID-19 from a cat than vice versa. DOI: 10.1056/NEJMc2013400

A team of biochemists and virologists at Goethe University and the Frankfurt University Hospital in Germany have discovered potential targets for COVID-19 therapy. In a cell culture model, several compounds were found to slow down or stop the SARS-CoV-2 virus. Based on the findings, published in Nature, U.S. company Moleculin Biotech reports that it will conduct a clinical trial of WP1122, a prodrug akin to 2-Deoxy-D-Glucose shown to stop viral reproduction in the cell culture system. Canadian company Bausch Health Americas has also announced it is starting a 50-participant clinical study of Ribavirin, another one of the substances tested in Frankfurt. The virus was cultivated in colon cells from swabs taken from two infected individuals returning from Wuhan. Scientists used a form of mass spectrometry called the mePROD method, developed only a few months previously, which makes it possible to determine the amount and synthesis rate of thousands of proteins within a cell. SARS-CoV-2 infection leads to an increased protein synthesis machinery in the host cell and this was a weak spot of the virus, allowing them to shut down protein production using translation inhibitors. DOI: 10.1038/s41586-020-2332-7

Other News |

Entos Pharmaceuticals is partnering with Precision Nanosystems, Inc. (PNI) to manufacture its DNA COVID-19 vaccine Covigenix and other genetic nanomedicines using PNI’s NanoAssemblr GMP System, which will be added to the Alberta Cell Therapy Manufacturing facility in the University of Alberta's Li Ka Shing Centre for Health Research Innovation. Entos develops next-generation, nucleic acid-based therapies using the proprietary Fusogenix drug delivery system, a proteo-lipid vehicle that delivers molecules, intact and unmodified, directly into the cytosol of target cells. The company recently launched a DNA vaccine rapid prototyping project around the development of a pan-coronavirus DNA vaccine, with the aim of broad availability within one year. Press release.  

Leaders from some of the world's top X-ray facilities, including Advanced Photon Source at the U.S. Department of Energy’s Argonne National Laboratory have developed a strategy for cooperatively combating COVID-19 via new drugs, therapeutic strategies and medical equipment. At a virtual summit last month, they developed an action plan that includes development of a shared IT system to accelerate the process of information distribution, as well as exchange of experiences with remote access and sample mail-in procedures. Press release.  

Thanks to the efforts of University of the Western Cape and Stellenbosch University, South Africa obtained its first known laboratory isolate of SARS-CoV-2 on April 1. This will allow researchers to supply diagnostic labs with large amounts of virus genetic material that is identical in genetic makeup and concentration, offering opportunities for further research and providing reference material for standardizing diagnostic tests across multiple platforms between laboratories. The lives virus was created from clinical samples taken from COVID-19-positive patients at a hospital in Cape Town and inoculated onto live cells cultured in the laboratory. The growth requirements of SARS-CoV-2 are like that of SARS-CoV-1, which gave researchers a roadmap. One of the greatest limitations in growing SARS-CoV-2 is the need to be a “biosafety level-3" lab, which are scarce, and in South Africa most such labs lack the setup for dealing with respiratory viruses. Press release

Parexel has launched its COVID-19 Risk Mitigation offering, which leverages the company’s significant experience with global viral outbreaks as well as cGMP inspection and CMC review processes to ensure that manufacturers can safely and confidently continue operations through the COVID-19 pandemic. Parexel’s regulatory experts will partner with life sciences companies to ensure business continuity during these challenging times by rigorously analyzing manufacturing operations to reduce the risk of viral contamination. This will be accomplished through a four-step methodology, including risk assessment, development of a risk mitigation action plan, implementation of solutions and routine re-assessment to ensure companies are supported over time and as circumstances change or new risks arise. Press release.  

UK-headquartered iPSC disease modelling company DefiniGEN has identified iPSC-derived intestinal organoids that could be used to help structure in vitro studies of the biology of SARS-CoV2 infection across cohorts of multiple patients. While SARS-CoV-2 primarily targets the respiratory system, studies have shown that it also infects and multiplies within the intestinal epithelium. IPSC-derived organoids exhibit characteristics that closely mimic the in vivo intestinal epithelium, making them a valuable surrogate model for studying the virus. Press release.  

Ramot, Tel Aviv University's technology transfer company, and Neovii, a Swiss-based biopharmaceutical company and a member of Israel-based Neopharm Group, have signed a research and license agreement to develop a COVID-19 epitope-based vaccine that will target the most vulnerable part of the viral spike protein—its receptor-binding motif (RBM). Reconstruction of the RBM will be the basis of the vaccine, which could be ready for use in 12 to 18 months. Press release

An international team of more than 30 computational scientists, medicinal chemists, biochemists, and virologists joined forces to rapidly screen millions of small molecules that inhibit SARS-CoV-19 replication by leveraging some of the world’s most powerful supercomputers. The COVID-19 Drug Discovery Consortium is now moving quickly to test the most promising candidates against the virus in high containment facilities. The most potent antiviral compounds will transition to manufacturing and safety/toxicity studies in preparation for first-in-human clinical studies. The effort originated with researchers who previously used the Drug Discovery @ TACC portal of the University of Texas Medical Branch and Texas Advanced Computing Center, launched in 2015, which helped hundreds of researchers find promising drug leads for other, non-coronavirus, diseases. Consortium members have settled on seven potential viral protein targets to screen drug-like molecules against and come up with 20 likely 3D models of the virus that show where a drug might bind in a way that changes the virus's shape or disrupts its function. The small molecules being screened are all readily available for purchase from Enamine Chemical Company. The compounds will be tested at Boston University’s level 4 screening facility. Press release

The Institute of Cancer Research (ICR, London) has fast-tracked development of the database Coronavirus canSAR , driven by artificial intelligence (AI), to warehouse the world's coronavirus research in a single online space. It is an adaptation of an existing system that pulls together data from across cancer research and drug discovery. The new resource will make freely available vast amounts of data on the biology and treatment of COVID-19, accelerating the search for new drugs and knowledge sharing across international boundaries to understand and overcome the disease. Included are data on viral proteins, interactions of viral proteins with human proteins, drugs and drug mechanisms, and more than 1,100 COVID-19 clinical trials. It is believed to be the world's first one-stop shop for research on COVID-19 and related diseases such as SARS and MERS. The knowledgebase, updated weekly, pulls in every 3D structure of biological molecules published in the international Protein Databank (450,000 so far). ICR has analyzed more than four million sites across all proteins in its database, including more than 8,000 from coronavirus protein structures and have identified several druggable cavities. Coronavirus-CanSAR uses AI to generate complex 3D maps of how virus and human proteins interact that resemble visualizations of space and highlight interactions that could potentially be disrupted with new drugs. ICR researchers have used the map to find new druggable sites at the interfaces of coronavirus and the critical proteins ACE2 and B(O)AT1, which is guiding development of new antibodies. Press release

University of Alberta (U of A) researchers have teamed up with U.S.-based Tonix Pharmaceuticals to develop and test a vaccine against COVID-19. The vaccine’s unique delivery method—synthetic vaccinia and horsepox viruses (poxviruses)—is ideally suited to deliver antigens needed to invoke an immune response against a virus like SARS-CoV-2, they say. The antigens are SARS-CoV-2 proteins that the poxvirus has been engineered to make and supply for processing by the immune system. The U of A team is proposing to insert genes copied from the SARS-CoV-2 virus genome into Tonix's proprietary vaccinia and horsepox viruses, then test whether they are expressing SARS-CoV-2 proteins, including the spike protein critical for infection. Press release

Biomedical visualization studio Visual Science reports that is has created the most detailed and scientifically accurate 3D model of the full SARS-CoV-2 virus at atomic resolution. The model is based on the latest scientific research on the structure of coronaviruses and communication with virologists currently working with the virus and was generated with the same structural bioinformatics techniques used in basic research and drug development. It is part of the company’s non-commercial Viral Park project, which also includes award-winning HIV virion and Ebola virus models. The detailed SARS-CoV-2 model shows the intact particle with its spike glycoproteins embedded in the membrane and a cutaway view reveals the viral nucleocapsid inside the particle. Press release.

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