October 23, 2020 | A global survey finds mixed responses to vaccine views and in the US they are driven partially by politics, neuropilin-1 facilitates virus entry, CRISPR identifies commonalities between the lethal coronaviruses, and early results on a Chinese vaccine. Plus: the University of Liverpool investigates how COVID-19 impacts the brain, Centivax and Thermo Fisher sign licensing agreement, and a call to action for the upcoming flu season.
Research Updates
A global survey published in Nature Medicine of 13,426 people in 19 countries found that 71.5% of participants reported that they would be very or somewhat likely to take a COVID-19 vaccine, and 61.4% reported that they would accept their employer’s recommendation to do so. Differences in acceptance rates ranged from almost 90% (in China) to less than 55% (in Russia). Respondents reporting higher levels of trust in information from government sources were more likely to accept a vaccine and take their employer’s advice to do so. DOI: 10.1038/s41591-020-1124-9. A separate study, published in JAMA Network Open, identified vaccine-related attributes (eg, vaccine efficacy, adverse effects, and protection duration) and political factors (eg, US Food and Drug Administration approval process, national origin of vaccine, and endorsements) as factors influencing whether or not US adults would take a COVID-19 vaccine. DOI:10.1001/jamanetworkopen.2020.25594
An international research team under German-Finnish coordination has identified neuropilin-1 as a factor that can facilitate SARS-CoV-2 entry into the cells' interior. Neuropilin-1 is localized in the respiratory and olfactory epithelia, which could be a strategically important localization to contribute to SARS-CoV-2 infectivity and spreading. The findings were published in Science. Pathological analysis of human COVID-19 autopsies revealed SARS-CoV-2 infected cells including olfactory neuronal cells facing the nasal cavity positive for NRP1, the authors write, providing insight into SARS-CoV-2 cell infectivity and defining a potential target for antiviral intervention. DOI: 10.1126/science.abd2985
There are common vulnerabilities among three lethal coronaviruses, SARS-CoV-2, SARS-CoV-1 and MERS-CoV, such as frequently hijacked cellular pathways, that could lead to promising targets for broad coronavirus inhibition, according to a study by a large international research team published in Science. They generated and compared three different coronavirus-human protein-protein interaction maps in an attempt to identify and understand pan-coronavirus molecular mechanisms. Researchers ran analyses on Real-Time Insights and Evidence, an instance of the Aetion Evidence Platform with real-time health care data generated evidence on prospective treatments for COVID-19. Synthego delivered multiple CRISPR-based engineered cell lines to accelerate the study of potential treatment targets for SARS-CoV-2. Their results suggest that protein localization can often differ when comparing individually-expressed viral proteins with the localization of the same protein in the context of infection. DOI: 10.1126/science.abe9403
An international team profiled the lung and colon transcriptomes and lung proteomes of nine patients who died of COVID-19 during the first wave of the pandemic in Wuhan, China, and published their findings in PNAS. They found little virus present in lung tissue at the time of death suggests that these patients may have died of sequelae related to COVID-19 pneumonia (i.e., the host inflammatory response) rather than an ongoing, fulminant active viral infection. Although there is no obvious pathogenesis in the colon tissue based on histological examination, there is a dramatic change in the transcriptome in the colon tissues in the fatal cases when compared to healthy controls. These findings inform the treatment choices of COVID-19 patients, the authors write. DOI: 10.1073/pnas.2018030117
A group of Chinese researchers has released a molecular docking-based webserver, D3Targets-2019-nCoV, to predict drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies and identify lead compounds against potential drug targets via docking. The freely available server contains 42 proteins, 20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release, with 69 different conformations/structures and 557 potential ligand-binding pockets in total. DOI: 10.1016/j.apsb.2020.04.006
A Chinese team reports preliminary results from a vaccine candidate, BBIBP-CorV, based on inactivated SARS-CoV-2 virus that is safe and induces an immune response in healthy volunteers, they say in Lancet Infectious Diseases. The Phase 1/2 randomized controlled trial of an inactivated SARS-CoV-2 vaccine candidate was carried out in China between 29 April and 30 July 2020 and involved more than 600 healthy volunteers. The study detected antibody responses in all recipients by day 42 after vaccination and provides some data for participants aged over 60 years. DOI: 10.1016/S1473-3099(20)30831-8
Asymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a major contributing factor in skilled nursing facility (SNF) outbreaks, say a team of Brown researchers in a Research Letter published in JAMA Internal Medicine. Using data from a multi-state care provider, the team reviewed data from 350 SNFs between March and July. They observed high asymptomatic and presymptomatic SARS-CoV-2 infection rates in a large multistate sample of SNFs, demonstrating the importance of universal testing for identifying and isolating cases. DOI: 10.1001/jamainternmed.2020.5664
Cannabidiol (CBD) may ameliorate the symptoms of acute respiratory distress syndrome (ARDS) through up‐regulation of apelin, a peptide with significant role in the central and peripheral regulation of immunity, CNS, metabolic and cardiovascular system, researchers showed in a mouse model. CBD treatment increased the apelin expression significantly, suggesting a potential crosstalk between apelinergic system and CBD may be the therapeutic target in the treatment of inflammatory diseases such as COVID‐19 and many other pathologic conditions. The results are published in the Journal of Cellular and Molecular Medicine. DOI: 10.1111/jcmm.15883
A team from the University of New Mexico screened 4,000 approved drugs for structural similarity to hydroxychloroquine, theorizing that similar drugs may be useful in COVID-19 treatment. They found several that efficiently block SARS-CoV-2 infection and propose zuclopenthixol, nebivolol, and amodiaquine as potential candidates for clinical trials against the early phase of the SARS-CoV-2 infection and discuss their potential use as adjuvant to the current (i.e., remdesivir and favipiravir) COVID-19 therapeutics. They publish their findings in ACS Pharmacology & Translational Science. DOI: 10.1021/acsptsci.0c00131
American and Polish scientists, reporting in Science Advances, laid out a novel rationale for COVID-19 drug design: blocking an enzyme called SARS-CoV-2-PLpro that the virus uses for virus production and to disable human proteins crucial to the immune response. The team designed optimal fluorogenic substrates and irreversible inhibitors with a high degree of selectivity for SARS PLpro and confirmed the inhibitory mechanisms via crystal structures of two of these inhibitors in complex with SARS-CoV-2 PLpro. The authors say the work has revealed the molecular rules governing PLpro substrate specificity and provides a framework for development of inhibitors with potential therapeutic value or drug repurposing. DOI: 10.1126/sciadv.abd4596
In the journal PeerJ, Duke researchers used statistical methods they developed to identify adaptive changes that arose in the SARS-CoV-2 genome in humans, but not in closely related coronaviruses found in bats and pangolins. They flagged mutations that altered the spike proteins, suggesting that viral strains carrying these mutations were more likely to thrive, and also found mutations in two other regions of the SARS-CoV-2 genome, Nsp4 and Nsp16. These changes likely affected how the virus's RNA folds up into 3-D shapes and functions inside human cells. DOI: 10.7717/peerj.10234
A University of Hong Kong team reports a class of metallodrugs currently used in the treatment of other infectious diseases is showing efficacy to potently suppress SARS-CoV-2 replication and relieve viral-associated symptoms in an animal model. Ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, is a potent anti-SARS-CoV-2 agent, both in vitro and in vivo they say in a study published in Nature Microbiology. DOI: 10.1038/s41564-020-00802-x
Industry Updates
Centivax, the therapeutics spinout of Contract Research Organization Distributed Bio, has announced a licensing agreement with Thermo Fisher Scientific. Thermo Fisher has developed and evaluated several variants of Centivax's highly specific and effective therapeutic antibody candidates against COVID-19 for use in research, including flow cytometry, histopathology, in vitro and in vivo neutralization, Luminex and ELISA applications. These products are now commercially available to academic and industry research laboratories. Centivax's engineered antibodies have been validated for potency and efficacy both in vitro and in vivo, protecting an animal model of hamsters from SARS-CoV-2, the virus that causes COVID-19. Press release.
The University of Liverpool is leading a new global project to better understand how and why COVID-19 affects the brain in order to develop measures to help improve patient outcomes. The University has secured £860,000 from the National Institute for Health Research (NIHR), in partnership with UK Research and Innovation (UKRI) to establish the COVID-Neuro Global program in partnership with five leading research organizations in Brazil, India and Malawi. The researchers plan to compile data from patients across the world to create a single large report of the full range of neurological disease in COVID-19. The team will also carry out research studies with COVID-19 patients in hospitals in Brazil, India and Malawi to identify risk factors for neurological disease, especially those which can be treated, such as lack of oxygen in the blood. They will also look at outcomes for neurological patients, to help better understand what might predict a poor outcome. Press release.
The National Foundation for Infectious Diseases (NFID) issued a new Call to Action report detailing the risks of co-infection with influenza (flu) and COVID-19 in adults with chronic health conditions, and the importance of flu vaccination during the 2020-2021 season. The goals of the report, The Dangers of Influenza and COVID-19 in Adults with Chronic Health Conditions, have been supported by more than 35 leading medical organizations, including the American College of Cardiology, American College of Emergency Physicians, American Diabetes Association, and American Lung Association, who are now urging their stakeholders to prioritize flu vaccination for these high-risk populations. Call to Action.
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October 23, 2020 at 11:45AM
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Vaccine Outlook Mixed, Commonalities Between Coronaviruses, Brain Impacts: COVID-19 Updates - Bio-IT World
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