The world is racing to develop diagnostic tests, treatments and vaccines for the dreaded Covid-19 virus. Academics, Global Life Sciences and Pharmaceutical companies are combining knowledge, experience and expertise to defeat the pandemic. Below is a summary of some of the most important projects in UK nearing fruition and contributing to the Global effort.
The largest randomised clinical trial of possible coronavirus treatments has begun with 1,000 adult patients hospitalised in 130 different NHS hospitals. These patients will be being evaluated with Lopinavir-Ritonavir (commonly used to treat HIV), Dexamethasone, (a commonly used steroid to reduce inflammation) and Hydroxychloroquine, a treatment for malaria and Azithromycin (a commonly used antibiotic). The data obtained from these RECOVERY trials will be regularly reviewed so that any effective treatment can be identified quickly and made available to all patients. This being coordinated by researchers at the University of Oxford, led by Peter Horby, Professor of Emerging Infectious Diseases and Global Health and Martin Landray, Professor of Medicine and Epidemiology.
University of Oxford researchers are working in an unprecedented manner towards the vaccine development effort to prevent COVID-19. A recent screening of healthy volunteers (aged 18-55) was carried out for their upcoming ChAdOx1 nCoV-19 vaccine trial. The vaccine based on an adenovirus vaccine vector, and the SARS-CoV-2 spike protein is already in production but will not be ready for some weeks. The trial will provide valuable information on the safety aspects of the vaccine, as well as its ability to generate an immune response against the virus. The trial, a collaboration between the University’s Jenner Institute and Oxford Vaccine Group clinical teams, will recruit up to 510 volunteers, who will receive either the ChAdOx1 nCoV-19 vaccine or a control injection for comparison. Detailed preclinical work is being done and the vaccine is being manufactured to clinical-grade standard at the Clinical Biomanufacturing Facility at Oxford University. The trial has been approved by UK regulators and ethical reviewers. Researchers are working as quickly as possible to get the vaccine ready to be used in the trial, which includes further preclinical investigations and production of a larger number of doses of the vaccine.
Diamond, the UK’s national synchrotron light source, have a joint initiative with Exscientia, the leading artificial intelligence driven drug discovery company and Calibr, the drug development division of Scripps Research, to search for FDA clinically approved drugs that could be viable clinical drug candidates for the rapid treatment of COVID-19. The collection of clinical drug molecules is being shipped from the Scripps Research in California to Exscientia in Oxford, UK. Exscientia will be applying biosensor platforms to screen them against several viral drug targets of SARS-CoV-2, the virus responsible for COVID-19. These targets include; the 3CL protease and the NSP12-NSP7-NSP8 RNA polymerase complex – both of which are vital components for how the virus replicates – and the interaction between the virus’s SPIKE protein and the human cell receptor ACE2, which enables the viruses’ entry to human cells. Diamond Light Source and Oxford University have been working together since January to develop methods for the production of the viral proteins for drug screening and structural analysis at Diamond on the Harwell Campus, which can provide an atomic level of detail in understanding how anti-viral drugs can work against the virus.
PostEra Inc. a start-up international group of scientists from academia and industry have teamed up to form a new, ground-breaking non-profit initiative – the COVID Moonshot. The name derives from its unprecedented aim to develop a clinically effective antiviral more rapidly than ever before, by crowdsourcing designs of new inhibitors from chemists around the world who are mining the massive crystal-based fragment screen, revealed the XChem facility at UK’s Diamond Light Source. Data will be measured in record time during March and April. All data will be released in real-time and in the open to enable worldwide collaboration and rapid progress. Chemists are being called on to come up with new molecules and to have a practical input towards the global efforts to combat COVID-19. Researchers can submit their designs to PostEra, who will be running machine learning algorithms in the background to triage suggestions and generate synthesis plans to enable a rapid turnaround. Promising compounds will then be synthesized and tested for antiviral activity and toxicity. This new approach is already paying dividends, following just two rounds of designs, the team has received over 3500 molecular design contributions and the first compounds will be tested this week. A paper is close to submission and they have already identified at least one serious therapeutic possibility at Oxford.
Oxford Nanopore Technologies (ONT) aims to disrupt the paradigm of biological analysis by making high performance, novel DNA/RNA sequencing technology that is accessible and easy to use by anyone, anywhere. The portable MinION can sequence the SARS-CoV-2 virus (responsible for COVID-19) in 7 hours. ONT’s sequencing technology offers real-time analysis in fully scalable formats that can analyse native DNA or RNA and sequence any length of fragment to achieve short to ultra-long read lengths. Sequencing the novel coronavirus SARS-CoV-2 and metagenomic sequencing of other pathogens or microorganism present in the sample can support ‘genomic epidemiology’. Thus characterising the virus and helping public health authorities understand the identity of the virus, whether it is changing and how it is being transmitted- in conjunction with all the other epidemiological data. ONT is working with public health labs and related researchers around the world to support the pandemic.
Diagnostic research to increase the UK’s testing capacity, new vaccine targets, understanding more about people who are asymptomatic, and digital support for people with diabetes, are some of the 25 new projects announced by the University of Bristol that will undertake vital COVID-19 research to tackle the global health crisis. A project to help increase the UK’s testing capacity is being led by Adam Finn, Professor of Paediatrics at Bristol, Director of the Bristol Children’s Vaccine Centre at Bristol Medical School and lead of Bristol UNCOVER (Bristol COVID Emergency Research), a group of Bristol researchers. Prof Finn’s lab is establishing quantitative real-time PCR tests which enable scientists to look for the genetic sequences specific to the virus and show if someone is infected at the time of testing. Currently used by Public Health England (PHE) to test patients and NHS staff, the team will use PCRs to validate other tests and kits to check they are reliable enough so that capacity could be scaled-up. The team also plan to analyse swab samples taken as part of other research studies during recent weeks to chart the early stages of the epidemic.
Professor Imre Berger, Director of the Max Planck-Bristol Centre for Minimal Biology with scientists from Bristol biotech start-up Imophoron are using ADDomer©, their innovative rapid response synthetic virus-like particle (VLP) platform to develop new COVID-19 candidate vaccines, apparently with a reduced risk of side effects. By inserting harmless bits of the viral surface proteins into the VLP platform they generated SARS-CoV-2 virus-like mimics. These ADDomer©-COVID19 candidate vaccines exploit the virus’s ‘Achilles Heel’ epitope – critical for reducing the virus’s infectivity. Prof Berger said: “Our aim is to perform animal immunisation and virus neutralisation experiments, then move towards a bona fide vaccine and into trials as soon as possible.”
A new testing laboratory is being set up by GSK, AstraZeneca and Cambridge University’s Anne McLaren laboratory for Regenerative Medicine. This facility will be used for high throughput screening for COVID-19 testing and to explore the use of alternative chemical reagents for test kits in order to help overcome the current supply shortages. The partnership will also provide expertise in automation and robotics to help the national testing system to continue to expand capacity.
BioSure in Sussex, who are known for their HIV Self-Test, are working on the antibody self-test for those who have had the virus in the past, whether with or without symptoms and are no longer infectious and they probably have immunity- no detectable SARS-CoV- 2 antigen but have COVID 19 antibodies. With their world-leading molecular diagnostics partner BioSure have a test and are now in the process of validation. The BioSure Covid-19 self-test is based in its entirety upon their pre-existing and highly accurate HIV Self- test kit which is CE certified for self -use and has been successfully in the market since 2015, supplying to both healthcare and directly to consumers. This was the highest risk vitro diagnostic device to be granted a CE mark. The device, the design, instructions and test result interpretation are identical, the only difference is that the test strip inside the device will detect antibodies to SARS- CoV-2 as opposed to antibodies to HIV, hence to help identify people who have been infected by the virus.
This is just a sample of all the brilliance and collaboration the coronavirus has triggered in UK, demonstrating how Britain is a world leader in innovation.