Objectives

Highly potent and safe directly-acting antiviral drugs are available for the treatment of a number of chronic viral infections like HIV (~30 approved drugs, used in efficient combinations) and hepatitis C virus (HCV). In the latter case, a very well tolerated, two-month therapy of one or two pills per day now allows to cure ~99% of the patients with chronic HCV. This demonstrates how successful potent and specifically-developed antiviral drugs can be.

Highly 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 active against 2019-nCoV, and also against MERS-CoV and any other member of this large virus family that could emerge in the future and cause an epidemic. Such drugs would allow treatment of SARS-CoV-2 infected patients, and in particular save the lives of those that become critically ill. Importantly, as long as vaccines are not available or when the virus would escape from vaccine-induced immune responses, effective measures are also urgently needed to protect the direct contacts of infected patients, including health-care workers and household members. As in influenza control, such antiviral prophylaxis can be an important weapon to control outbreaks. By reducing virus shedding by infected patients, their direct contacts can be protected as well. In this manner, sufficiently potent prophylactic drug treatment should allow to reduce the R0 to below 1, which would be an essential tool for worldwide efforts to curb the epidemic.

Therefore, it is the primary and urgent objective of the SCORE consortium to develop antiviral therapy to combat SARS-CoV-2, and coronaviruses in general. We will develop a tailored SARS-CoV-2 -specific toolbox withreagents, assays, and protocols, efforts that will be importantly supported by our vast experience with the closelyrelated SARS-CoV. In parallel, drug discovery efforts will be started immediately, using four independent tracks to target a range of key SARS-CoV-2 replicative enzyme functions and the viral entry process. Our first aim isto identify (within the next few weeks) inhibitors of SARS-CoV-2 replication by screening libraries of approved drugs,or molecules that have gone through some stage of clinical development for other indications. As these inhibitorsmay not be sufficiently potent on their own, we will also establish (in vitro, ex-vivo and in small animal infectionmodels), if specific drug combinations are more potent and may directly be considered for clinical trials. The secondaim is to discover/develop highly potent and directly-acting (pan-)coronavirus inhibitors. To that end the consortiumwill use (i) a target-based approach to inhibit viral entry, viral proteases or the viral RNA polymerase, and (ii) high throughputphenotypic antiviral screens in cell culture-based SARS-CoV-2 infection models. The latter approach willallow the identification of antiviral hits that will be further optimized using a medicinal chemistry approach.

Moreover, these molecules will be employed to map 2019-nCoV drug targets at the molecular level and uncover the Achilles’ heel(s) of viral replication. This will yield essential information for novel target-based drug development strategies. The SCORE partnership is uniquely shaped to dampen the economical and public-health threats of present and future emerging coronaviruses. The intersectoral SCORE consortium incorporates highly complementary expertise to pilot, deliver, and transfer anti-coronavirus drugs and the associated high-end research to our societies.