Fighting coronavirus: European supercomputers join forces with pharmaceutical companies in hunt for new drugs
Exscalate4CoV (E4C) consists of a coalition between public and private partners located across seven European countries (Belgium, Germany, Italy, Poland, Spain, Sweden and Switzerland), working together to combat the spread of the novel coronavirus. Coordinated by the Italian pharmaceutical company Dompé and disposing of the best researchers in their respective fields, along with three powerful high-performance computing (HPC) centres in Bologna, Barcelona and Jülich, E4C is searching for potential drugs to fight the COVID-19 disease.
With new contributors from the pharmaceutical industry, research institutions, and biological laboratories signing non-disclosure agreements with E4C on an almost daily basis, the chances of finding molecules to create an antiviral medication continue to grow. Eight European companies – Pierre Fabre, Alfasigma, Almirall, Axxam, Esteve, Lilly, Sanofi and Greenpharma – have already joined the scheme since 10 April 2020, and discussions with other companies are now in the works, such as Merck, Takeda, Abbott and many more.
Pharma companies are opening their medical libraries to testing and donating molecules via the online DrugBox data platform to provide E4C access to new and existing drugs, enlarging its database and increasing the probability of identifying and producing a fully repurposed treatment.
The strengths of Exscalate4CoV emerge from synergies between the partners’ different scientific backgrounds. The project will build on two distinct but interconnected streams of activities, both converging to the biological screening. One mostly relies on supercomputer capacities, in combination with artificial intelligence (AI), bioinformatic and chemoinformatic technologies. The other combines the available project knowledge with a genomic, biochemical and biological approach so as to identify interesting molecules that could be used for a potential drug.
The first step is to obtain the structure of the virus. Three partners – the International Institute of Molecular and Cell Biology (IIMCB), Elettra Sincrotrone Trieste and the Swiss Institute of Bioinformatics (SIB) – use their technologies to crystallise the virus’ protein and provide its 3D structure. E4C has identified 25 different protein models that are constantly evolving, with various mutations received weekly, which are translated into a digital form for further testing.
The next step is the docking operations. E4C has a database of over 10,000 drugs and 500 billion molecules; with a computing capacity of 50 million billion operations per second, the three European supercomputers are able to match the digital signature of coronavirus proteins against molecules from the chemical library, in the aim of identifying a drug and ultimately saving thousands of lives. The pharma companies joining the project will provide new molecules under the DrugBox initiative, boosting the potential to find possible COVID-19 treatments.
From the initial implementation of its two working streams of activities, the project has already identified a set of 93 antiviral molecules, now under biological screening at KU Leuven, Fraunhofer IME and the University of Cagliari. These screenings determine the potency of each compound; 10 compounds have already been identified as promising candidates and are still under successive screening, with the hope that some could finally undergo clinical trials, in the hope for a possible cure to be used on patients in the upcoming months.
The virus multiplies by attaching itself to cells via its internal spiral structure, so the goal is to find a substance that could damage the spiral or inhibit its protein from sticking to other cells. As confirmed by Nobel Prize winner Dr. Robert Gallo, the coronavirus has a complex nature, and therapy will likely involve a cluster of different molecules rather than a single one.
