Defeating COVID-19: the race we will win together
Michel Pairet, Member of the Board of Managing Directors, Innovation
Clive R. Wood, Global Head of Discovery Research, Boehringer Ingelheim
We are all in a race to find solutions to halt the catastrophic toll on human health and wellbeing that COVID-19 is exacting. Two things will ensure success in fighting this pandemic: first, we are all standing together in open collaboration for common cause; and second, we will succeed because of science.
It is alarming how much misery and havoc that the 29,903 ribonucleotide bases of SARS-CoV-2 have inflicted upon the world. However, no pandemic threat has previously faced the combined intellect and technology of 21st century science, with lines of communication powered by the internet and rapid research publications open to all. Humanity and its scientific community are united in a way that is unprecedented in our lifetimes. And we are using all our scientific capabilities and committing them in an international spirit of open science on a scale that has never been seen before.
As early as mid-January we started to consider how Boehringer Ingelheim could best help. We started to work on two key questions:
How can we re-direct existing products and drug candidates to combat SARS-CoV-2?
We reviewed our clinical and preclinical pipelines. We asked whether we may have compounds that could work directly against the virus, or compounds that might ameliorate the course of the disease in the most severely affected patients. This included using our extensive background in respiratory and cardiovascular diseases. As of today, we are investigating a number of potential opportunities that include:
Our tissue plasminogen activator alteplase (Actilyse®), following case reports suggesting potential to block hypercoagulation and prevent organ failure in severely ill COVID-19 patients.
Direct-acting antiviral small molecule compounds from previous virology projects, such as polymerase and protease inhibitors from our legacy HIV and HCV research.
The potential of our Inflammation and Cardiometabolic Diseases portfolio, including preclinical and early clinical stage drug candidates to address the hyperinflammation and epithelial/vasculature pathologies.
How can we discover new drugs that combat SARS-CoV-2?
Our scientists are using four platforms to generate monoclonal antibodies against the SARS-CoV-2 spike protein: human antibody phage display; immunized human antibody transgenic mice; antibodies isolated from the blood of people who have recovered from infection; and computational structure-based antibody design. It is already paying off: we have identified first candidates and partner laboratories are testing them for viral neutralizing effects.
In parallel to our work on antibodies, we are using all of our expertise in medicinal chemistry and chemical assets to find small molecule inhibitors. We are screening our entire molecular library of more than one million compounds to identify those with potential activity to treat COVID-19. Our teams are using computational screening to speedily search this huge resource, starting with two priority viral targets: SARS-CoV-2 main protease and SARS-CoV-2 papain-like protease1. The expertise we have built in artificial intelligence-aided optimization of drug candidates will speed our path.
As important as identifying the best therapeutic candidates will be how quickly we can go from discovery to clinical testing. Our plans are advanced to do this at a record-breaking pace.
Joining forces in new collaborations
Boehringer Ingelheim researchers are active members of innovative collaborative approaches bringing together world-leading scientists from across the world, including:
A fast-track call initiated by the Innovative Medicines Initiative (IMI) of the European Union, bringing together industry and academic researchers to develop existing or new treatments to respond rapidly to COVID-19.2
The COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation in a unique collaboration across the life sciences industry to help address this global health emergency and prepare for future public health challenges.3
These partnerships are moving very rapidly with an unprecedented spirit of co-operation to push the boundaries of biomedical progress.
Science serving society
We are starting to make progress in the fight against COVID-19 although there will inevitably be twists and turns ahead. However, we are confident that biomedical science and our industry will succeed in playing a critical part in defeating this menace. It is an opportunity for the power of open science and collaboration to shine in the service of society. The race is on and we know it is a race we will win together.
References
1. Zhang L, Lin D, Sun X et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. https://science.sciencemag.org/content/368/6489/409
2. IMI launches EUR45m call for proposals on the coronavirus. 3 March 2020. https://www.imi.europa.eu/news-events/press-releases/imi-launches-eur-45m-call-proposals-coronavirus
3. Bill & Melinda Gates Foundation. Life sciences companies commit expertise and assets to the fight against COVID-19 pandemic alongside Bill & Melinda Gates Foundation. 25 March 2020. https://www.gatesfoundation.org/Media-Center/Press-Releases/2020/03/Life-Science-Companies-Commit-to-the-Fight-Against-COVID-19-Pandemic-alongside-Gates-Foundation