Antiviral unveiled that goes after multiple coronaviruses

At the American Chemical Society Spring 2025 meeting on Tuesday, Ed Griffen of MedChemica disclosed the structure of a pancoronavirus antiviral that targets the main protease (M^pro ) of the two different coronaviruses that cause Middle East respiratory syndrome (MERS) and COVID-19. The antiviral, ASAP-0017445, was presented as part of a digital session titled “Developing Countermeasures for Viruses of Pandemic Potential” organized by the Division of Medicinal Chemistry of the ACS.

The work to build ASAP-0017445 was performed by researchers who are part of the ASAP (artificial intelligence–driven structure-enabled antiviral platform) Discovery Consortium, where Griffen heads up lead optimization. The ASAP team has been building on open-science antiviral discovery efforts started by the COVID Moonshot team during the early days of the COVID-19 pandemic.

Over the past 5 years, chemists around the world who participated in the open-science projects have proposed thousands of compound structures that might target the SARS-CoV-2 virus. Griffen explained that MERS-CoV is also a pathogen of concern for future pandemics. In addition, the virus presents a danger of recombination with SARS-CoV-2. So the team decided to expand its coronavirus work to pursue MERS as well.

That proved tricky, as the main protease of the MERS virus is less efficient at processing peptides, which means that the group’s lead compound for targeting the SARS-CoV-2 M^pro was too weak. Using structural data, the team found where it could extend the ligands in an attempt to increase the potency.

Griffen described how the group realized that it needed an amine at one end of the molecule and a heterocycle on the other. A combination of in vitro and in vivo tests, as well as machine learning, helped the researchers optimize these two groups for potency, permeability, and stability.

Preclinical profiling of ASAP-0017445 is still ongoing, but Griffen said researchers at the pharmaceutical chemical provider Enamine have already started work on scale-up and have synthesized half a kilo of ASAP-0017445.

Griffen said that because there will always be new viral outbreaks, the team hopes that its pandemic preparedness efforts mean that drugs can get where they’re needed as quickly as possible when the time comes. In turn, that will help control outbreaks before they become pandemics.