AN INVESTIGATION OF THE INTERACTIONS OF COVID19 THERAPEUTICS REMDESIVIR AND MOLNUPIRAVIR WITH EQUILIBRATIVE NUCLEOSIDE TRANSPORTERS 1 & 2

Abstract

The bloodtestis barrier (BTB) is made up of phys ical, physiological, and immunological components which restrict the disposition of xenobiotics to the testes and permits some cancers and viral infections to persist after systemic clearance. The equilibrative nucleoside transporters (ENT) 1 and 2 allow s ome nucleoside analogs which treat these persistent infections to traverse the BTB. Along with Ebola virus, Zika virus, HIV, and others, SARSCoV2 may persist in the immune privileged site of the testis. Elucidating the transport mechanisms of nucleoside analogs active against this virus could be useful to prevent sexual transmission and relapse of Covid19. This study uses two HeLa S3 cell lines with ENT1 and ENT2 gene knockouts to investigate the interactions of Covid 19 therapeutics remdesivir and molnu piravir with the ENTs. LC-- MS/MS analysis was used to detect compound uptake by cells with and without the presence of ENT inhibitor NBMPR. These data show that molnupiravir is a weak inhibitor of the ENTs and remdesivir is a substrate that is able to trave rse the BTB. Development of compounds such as remdesivir which can both effectively treat Covid19 and cross the BTB should be a consideration during the development of novel therapeutics to treat this condition.