The rapid development of Covid-19 vaccines is a scientific triumph. But the recipes for making these vaccines are the exclusive intellectual property of pharmaceutical companies, which means countries cannot make an approved vaccine on their own, limiting distribution around the world. For this and other reasons, such as medical infrastructure issues and a lack of trained personnel to administer the vaccine, most poor countries will not be widely immunized until at least 2024.
Much of the process of finding a new drug or vaccine – as researchers seek out new candidates and companies develop them into safe and effective products – usually takes place behind closed doors. Even once a product is approved, patent protections prevent other manufacturers from making and selling it. Eventually, the patents expire; but some aspects of the vital science behind the development of these patented products – such as candidates that don’t work – often remain forever locked in corporate silos, hampering research that could prevent future pandemics.
A variety of molecular fragments bind to Mpro, one of the proteins on which SARS-CoV-2 relies to replicate. Design
a medicine that blocks Mpro could prevent the virus from reproducing.
We believe there is a better and fairer way to fight Covid-19 and any future pandemic: open science.
Open science works on the principle that any scientific result should be shared immediately, with no restrictions on its use. Some say open science won’t work for drug development because it removes financial incentives: without the promise of patent protections, they believe, no one will bear the costs and risks of discovering and developing new ones. medications. We do not agree.
In March 2020, we launched COVID Moonshot, which we believe is the first open science effort to develop an antiviral drug. We are now on the verge of bringing to the clinic an effective oral antiviral against SARS-CoV-2 (the virus that causes Covid-19), without patent protection. As soon as the drug is approved, any drug manufacturer in the world can make and sell it without needing a license, which brings the prices down.
It shouldn’t be a one-size-fits-all thing: we believe that open science drug discovery for current and future pandemics is a essential public service – a project that should be fully funded by governments for the benefit of their people.
The idea started from a Tweeter. At the start of the pandemic, structural biologist Martin Walsh released a 3D structure of one of the main proteins that SARS-CoV-2 must replicate. We knew that this protein was an interesting therapeutic target because it does not mutate easily, which can make a drug less effective. (In contrast, the peak coronavirus protein targeted by vaccines and therapeutic antibodies is more likely to acquire mutations.) The protein, called Mpro, is also present in other pathogenic coronaviruses, suggesting that any antiviral drug targeting Mpro has a good chance of being effective against future coronavirus pandemics.
As time is running out, we’ve decided to approach drug discovery in a whole different way – putting all of our work online and asking the international scientific community to contribute. Ideas immediately began to flow, and scientists around the world submitted more than 17,000 potential drug candidates targeting Mpro, each drawing on ideas and data generated by others.
We have synthesized and tested over 1,400 of these designs, using a network of collaborating laboratories including the Weizmann Institute of Science, the University of Oxford and Diamond Light Source. We have also forged partnerships with pharmaceutical companies (UCB, Boehringer Ingelheim), contract research organizations (Enamine, Sai Life Sciences), computer networks (Folding @ home) and charities (DNDi and LifeArc) which make donation of manpower and resources. This is a grassroots movement – our entire drug discovery process is based on crowdsourcing ideas, experiments, and support from the scientific community.
We now have potential drug candidates that appear to do a good job of blocking the virus, as well as satisfying a variety of other properties that are required for a drug that can easily be taken as a pill (such as surrender and stay in. the blood). This, in itself, is a remarkable achievement, which took just over a year – a dizzying timeline in drug development. It usually takes several years to get to where we are now.
Even though there are several vaccines that help protect many people from severe Covid contamination, we still need oral antivirals that can cure people once they are infected. A packet of shelf-stable pills are much easier to distribute, store, and administer around the world than vaccines, should only be used by those who contract or are exposed to the virus, and have the potential to suppress the loads completely. viruses to prevent symptoms and transmission.
We are currently working to identify funding partners to continue efforts in clinical trials over the next 12 months, and we are seeking grants and charities to ensure that any approved drug remains patent-free; we recently secured an £ 8million ($ 11million) grant from the Wellcome Trust for preclinical regulatory studies. If successful, we believe this would be the first time in history that a clinical drug candidate would be outsourced from scratch.
During a global crisis such as a deadly pandemic, this is how drug development should work. Society appears to have collectively decided that governments should not financially support efforts to discover new drugs, even on issues of great public health importance. We buy our drugs from pharmaceutical companies, who bear the risks and costs of discovery, development and associated failure, and in return, they charge the highest prices the market will bear.
With pandemics, this economic model does not work. Our most advanced compounds appear to be equally effective against the virus that caused the SARS epidemic in 2003. In other words, if we had looked for an antiviral in 2004, we could have developed drugs capable of suppressing the SARS epidemic. Covid-19 more than a decade ago. But no private entity was willing to bet that another SARS-related epidemic would occur during the term of a patent. This market failure has already cost the world millions of lives and possibly billions of dollars.
We understand that drug development doesn’t come cheap – it costs around $ 300 million to develop the antiviral Tamiflu, for example. (Tamiflu, however, made almost $ 1 billion in six months in 2009.) We estimate that we have spent about $ 1 million on supplies and other expenses so far, and that does not include time and costs. resources that we donated (which probably exceed $ 1 million). We estimate that we will need $ 50 million to $ 100 million to fund full clinical trials that will bring our new antiviral through regulatory approval, so it can be manufactured and distributed.
The discovery of drugs in open science contributes significantly to the public good. For example, as a by-product of our drug discovery effect, COVID Moonshot has generated – and released for free – nearly 50% of all available structural data on SARS-CoV-2 Mpro, and a multitude of biochemical data on Mpro inhibitors. .
This provides a detailed atlas that helps drug hunters navigate this key protein of SARS-CoV-2 and associated coronaviruses, eliminating years of wasted time in drug discovery efforts for future pandemics. It’s a rising tide that lifts all boats. Many companies keep this data private to maintain a competitive advantage, so that no one can learn from the failures of others, dooming to repeat the mistakes of others.
Governments should be responsible for addressing existential threats to society. Unlike most illnesses, which are personal in nature, a pandemic cuts the heart of civic life. Once an open science drug is approved, it can be quickly manufactured and sold cheaply around the world without legal barriers. Think how transformative that would be and what public service it would provide.
As scientists, we launched the COVID Moonshot in hopes of doing our part to provide equitable global access to antivirals. Our progress shows that open science drug discovery is scientifically viable. The ball is now in the court of policymakers to fund and deploy efforts like the Moonshot with patients. Until we begin to view infectious disease drug discovery as a public service, pandemics will continue to reoccur and no one will come out unscathed.
This article originally appeared in Knowable Magazine, an independent journalistic company of Annual Reviews. Register to receive the newsletter.