How The SARS-CoV-19 Virus Attacks Cells, Other COVID-19 News
July 2, 2020 | New research shows how the SARS-CoV-19 virus shifts the cell's activity to promote its own replication and to infect nearby cells. This, plus more, are featured in this week’s COVID-19 news from the biotech and research industries.
Research Updates
A team of researchers from EMBL's European Bioinformatics Institute (EMBL-EBI), the Quantitative Biosciences Institute's Coronavirus Research Group in the School of Pharmacy at University of California San Francisco (UCSF), the Howard Hughes Medical Institute, the Institut Pasteur, and the Excellence Cluster CIBSS of the University of Freiburg have published work in Cell that shows how the SARS-CoV-19 virus shifts the cell's activity to promote its own replication and to infect nearby cells. The team identified dozens of clinically-approved drugs that could disrupt these mechanisms, and recommended that seven of these compounds, primarily anticancer and inflammatory disease compounds, be immediately tested in clinical trials. DOI: 10.1016/j.cell.2020.06.034.
A Cold Spring Harbor team proposes that overactive neutrophils—a common type of circulating immune cell—may drive the life-threatening blood clots and inflammation that occur in some patients with COVID-19. High levels of the sticky, pathogen-trapping webs produced by the cells were associated with the most severe cases of COVID-19. The team studied 33 COVID-19 patients and 17 age and sex-matched controls. They found that NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19 and NETs may represent targets for therapeutic intervention. Their work was reported online in the journal Blood. DOI: 10.1182/blood.2020007008
Researchers at the Department of Energy's Oak Ridge and Argonne national laboratories have performed the first room-temperature X-ray measurements on the SARS-CoV-2 main protease, the enzyme that enables the virus to reproduce. The X-ray measurements mark an important first step in the researchers' ultimate goal of building a comprehensive 3D model of the enzymatic protein. The model will be used to advance supercomputing simulations aimed at finding drug inhibitors to block the virus's replication mechanism and help end the COVID-19 pandemic. Their research results are publicly available and have been published in the journal Nature Communications. DOI: 10.1038/s41467-020-16954-7
Investigators from Poland and Germany describe how excessive activation of the aryl hydrocarbon receptors (AhRs) by the SARS-CoV-19 virus via the IDO1-kynurenine-AhR signaling pathway leads to "Systemic AhR Activation Syndrome" (SAAS). The authors hypothesize that therapies targeting downregulation of AhRs and IDO1 genes should decrease severity of infection. Their work was published in Restorative Neurology and Neuroscience. DOI: 10.3233/RNN-201042.
Industry Updates
Sanford Burnham Prebys Medical Discovery Institute announced a research agreement with Eli Lilly and Company (Lilly) to characterize Lilly's next-generation anti-SARS-CoV-2 antibodies. These collaborative studies aim to build on Lilly's current portfolio of neutralizing antibodies by exploring novel cocktails, half-life extension technologies and strategies to further enhance potency. The research team will evaluate antibody candidates, delivered from Lilly through their partnership with AbCellera, using the live virus in the Institute's Biosafety Level 3 (BSL-3) laboratory. Press release.
Sherlock Biosciences and binx health have entered into a strategic partnership to develop a rapid, point-of-care diagnostic test for COVID-19 leveraging CRISPR technology. The organizations will combine the binx io diagnostic platform with SHERLOCK CRISPR technology to create a test that is robust and simple to use. The currently-available Sherlock CRISPR SARS-CoV-2 kit uses the SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) method to program a CRISPR molecule to detect the presence of a specific SARS-CoV-2 genetic signature in specimens collected from patients suspected of COVID-19 by their healthcare provider. The kit is intended for use in CLIA laboratories to assay nasal swabs, nasopharyngeal swabs, oropharyngeal swabs or bronchoalveolar lavage (BAL) specimens. This planned solution with binx health is designed to provide rapid and accurate results in a single patient visit across many diverse CLIA-waived settings, such as clinics, doctors’ offices, assisted living centers, pharmacies and other easily accessible consumer venues. Press release.
Entos Pharmaceuticals announced the selection of two lead candidates for a pan-coronavirus Fusogenix DNA vaccine (Covigenix) from its prototyping program launched at the onset of the global COVID-19 pandemic. The two lead Covigenix candidates show robust preclinical in vivo results, achieving all vaccine profile targets, including potency, ADE safety assessment, high immunogenicity, and efficacy. Lead Covigenix candidates stimulated neutralizing antibody levels and balanced T helper cell immunity in mouse models. In addition, no weight loss was observed at multiple doses of vaccine candidates. A $4.2M grant from the Canadian Institutes of Health Research (CIHR), Research Nova Scotia (RNS), and the Institute for Ageing (IA) will be used to further develop the Covigenix vaccine candidates through animal challenge studies and human clinical trials. Entos will partner with the Clinical Trials Research Center at the Canadian Center for Vaccinology (CCfV) in Nova Scotia, Canada to initiate Phase I/II human clinical trials which will evaluate the safety, tolerability, immunogenicity and efficacy of the Covigenix vaccine candidates in late July. Press release.
The Canadian Institutes of Health Research (CIHR) has awarded three University of Saskatchewan (USask) research teams a total of $900,000 to help strengthen Canada's rapid response to the COVID-19 pandemic. The projects will investigate the re-purposing of currently approved drugs to treat COVID-19 patients, evaluate some highly promising therapeutics against COVID-19, and help prepare for future outbreaks by gathering information on the best interventions public health officers have developed across the country. Press release. An additional $1.2 million from CIHR will focus on developing a saliva-based COVID-19 biomarker diagnostic test and prototype testing and examining COVID-19 incidence rates among Canadian dentists. Press release.
Zoic Labs and The Krogan Lab have partnered to make the SARS-CoV-2 Virus-Human Protein Interaction Map, an interactive data visualization tool that allows global scientists dynamic ways to visually connect with research. Coupled with the labs' SARS-CoV-2 protein-protein-interaction network, this Zoic Labs visualization can be a powerful tool for understanding the virus on a molecular level. It allows scientists around the world to share their findings and characterizes critical connections between the 27 SARS-CoV-2 proteins and the 332 human genes they interact with, lending a wealth of information about each gathered through research. The tool also provides in-depth knowledge about all current drug interactions and their statuses, and links to external sources for additional information about the virus proteins. More information.