Ferulic acid derivatives block coronaviruses HCoV-229E and SARS-CoV-2 replication in vitro

A novel coronavirus, SARS-CoV-2, emerged in China at the end of 2019 causing a large global outbreak. As treatments are of the utmost importance, drugs with broad anti-coronavirus activity embody a rich and rapid drug discovery landscape, where candidate drug compounds could be identified and optimized. To this end, we tested ten small-molecules with chemical structures close to ferulic acid derivatives (FADs) (n=8), caffeic acid derivatives (CAFDs) (n=1) and carboxamide derivatives (CAMDs) (n=1) for their ability to reduce HCoV-229E replication, another member of the coronavirus family. Among these ten drugs tested, five of them namely MBA112, MBA33, MBA27-1, OS4-1 and MBA108-1 were highly cytotoxic and did not warrant further testing. In contrast, we observed a moderate cytotoxicity for two of them, MBA152 and 5c. Three drugs, namely MBA140, LIJ2P40, and MBA28 showed lower cytotoxicity. These candidates were then tested for their antiviral propreties against HCoV-229E and SARS-CoV2 replication. We first observed encouraging results in HCoV-229E. We then measured a reduction of the viral SARS-CoV2 replication by 46% with MBA28 (EC50>200 mu M), by 58% with MBA140 (EC50=176 mu M), and by 82% with LIJ2P40 (EC50=66.5 mu M). Overall, the FAD LIJ2P40 showed a reduction of the viral titer on SARS-CoV-2 up to two logs with moderate cytotoxicity which opens the door to further evaluation to fight Covid-19.

Automated summary

In this study, several compounds were tested for their antiviral activity against coronaviruses, and one compound, FAD LIJ2P40, showed low cytotoxicity and significant reduction in viral titer of SARS-CoV-2, which opens up the possibility for further evaluation as a potential treatment for Covid-19.