Ecotoxicological data of selected antiviral drugs acting against SARS-CoV-2: Aliivibrio fischeri bioluminescence inhibition, Daphnia magna immobilization, and comparison with in silico predictions

Abstract

Micropollutants such as pharmaceuticals that are released into the environment after wastewater treatment may have a severe impact on organisms in the aquatic environment. Especially ecotoxicological effects of antiviral drugs have been insufficiently investigated up to date. As a result of SARSCoV-2, favipiravir, remdesivir and molnupiravir, as well as their metabolites GS-441524 and EIDD-1931, have become the focus of treatment options against the COVID-19 virus. Thus, this study investigated potential ecotoxicological effects of these substances to the aquatic organisms Aliivibrio fischeri (DIN EN ISO 11348-1:2008) and Daphnia magna (OECD No. 202). The concentrations of the test substances in the exposure media were quantified using high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight high-resolution mass spectrometry. During the bioluminescence inhibition test using A. fischeri, effective concentration values indicating 10% efficacy were found for favipiravir and molnupiravir, i.e. 9.3 mg∙L− 1 and 95.5 mg∙L− 1. For EIDD-1931, ecotoxicological data were obtained and could fill the gap in available databases. As the effective concentrations indicating 50% efficacy on the test organisms were determined to exceed 1400 and 1500 mg∙L− 1, no ecotoxicological hazards during exposure of EIDD-1931 on both A. fischeri and D. magna are expected. Ecotoxicity values were further predicted using quantitative structure-activity relationship regarding the test organisms green algae and D. magna. Predicted values did not correlate with the findings of the acute immobilization tests with D. magna, suggesting predictions should be considered with caution. In general, the ecotoxicological findings as well as the calculation of the risk quotients indicated no or low ecotoxicological risks emerging from the five substances tested.