The usage of ivermectin (ivm) to treat COVID-19 is controversial. A recent clinical study evaluated ivermectin alone and in combination with the antibiotic doxycycline for their ability to treat COVID-19 patients. Antiviral drugs are commonly paired with antibiotics to help prevent secondary infections. Surprisingly, ivermectin alone was more effective than when combined with doxycycline. These observations suggested doxycycline blocked or overcame the antiviral effects of ivermectin. The goal of this project is to understand biochemically how doxycycline is affecting ivermectin activity using mammalian tissue culture cells as a model system. Previous work from other labs has demonstrated ivermectin can inhibit mitochondrial function. Our group recently showed that hydroxychloroquine, another controversial COVID therapeutic, also inhibits mitochondria. Thus, we hypothesized that ivermectin anti-viral activity involves mitochondrial inhibition, and that doxycycline might be interfering with this activity. To test this hypothesis, ivermectin inhibition of mitochondrial ATP production was recapitulated in human tissue culture cells. ATP levels were measured as the emission of light using CellTiterGlo<sup>TM</sup>. Order of addition experiments suggest that doxycycline can block but not overcome ivermectin inhibition of mitochondria, which could have clinical implications for administering this drug combination to treat COVID-19.

Effects of doxycycline on ivermectin activity against COVID-19

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.