SWIFT CORONAVIRUS THERAPEUTICS RESPONSE
Highly potent and safe directly-acting antiviral drugs are already available for the treatment of a number of chronic viral infections like HIV and hepatitis C virus. Combinations of drugs with different mode of action, provided in daily pills, can suppress or even cure these viral infections. This demonstrates how successful and life-saving antiviral drug treatments can be.
Potent small-molecule antiviral drugs can without doubt also be developed against any other virus group, including coronaviruses. Ideally these would be pan-coronavirus antiviral drugs that are not only active against SARS-CoV-2, but also against other coronaviruses like the still circulating lethal MERS-coronavirus and other members of the coronavirus family that may cause another pandemic in the future. Such drugs would allow therapeutictreatment of covid-19 patients, and may also be applied prophylactically to protect people who come in direct contact with SARS-CoV-2 infected persons: like health care workers, frontline workers and teachers. By reducing virus shedding by infected patients, their direct contacts can be protected as well. In this manner, sufficiently potent prophylactic drug treatment should help to reduce the R0 to below 1, which would be an essential tool for worldwide efforts to curb the pandemic.
For all these reasons, at the very beginning of the SARS-CoV-2 pandemic, eight academic and commercial partners, with extensive expertise in coronavirus research and antiviral drug development, established the SCORE consortium.
The SCORE consortium aims to develop antiviral therapy to combat SARS-CoV-2, and coronaviruses in general. We have developed a tailored SARS-CoV-2-specific toolbox with reagents, biochemical and biological assays, virus strains, reverse genetics systems, animal models and a range of protocols. These efforts were importantly supported by our vast experience with closely related corona viruses.
Using this toolbox, major steps were made in the structure-function characterization of a number of of key viral drug targets, including both viral proteases, the RNA polymerase and methyltransferases, the proofreading exoribonuclease and the Spike protein. In parallel, our drug discovery efforts started already in February 2020.
Different strategies have been applied to discover and develop highly potent and directly-acting coronavirus inhibitors. To that end the consortium uses not only a target-based approach to inhibit viral entry or replicative enzyme functions, but also high-throughput antiviral screens in cell culture-based SARS-CoV-2 infection models. The latter approach has already been highly successful and identified a number of robust antiviral hits that are currently further optimized using a medicinal chemistry approach. During its first year, the SCORE research and development program yielded 21 peer-reviewed scientific publications, many of which appeared in leading journals https://www.score-cov.eu/Article/Publications.
In the coming year, the obtained hits will be further developed to improve their activity. These new compounds will also be employed as part of our ongoing efforts to dissect coronavirus molecular biology and evolution, map SARS-CoV-2 drug targets at the molecular level and uncover the Achilles’ heel(s) of viral replication. These studies will be essential in our preparation for future encounters with newly emerging coronavirus pandemic threats.
The SCORE partnership is uniquely shaped to dampen the economical and public-health threats of present and future emerging coronaviruses. Due to its intersectoral nature, the SCORE consortium incorporates highly complementary expertise to explore, deliver, and transfer anti-coronavirus drug candidates and the associated high-end research to our societies.