artemisone and Cytomegalovirus-Infections

We have recently shown that the artemisinin derivative artemisone, which was screened against malaria in human clinical studies, is a potent inhibitor of human cytomegalovirus (HCMV). Here we evaluated the antiviral effect of artemisone when employed in 2-drug combinations with approved and experimental anti-HCMV agents. Using the Chou-Talalay method, we found that in-vitro combination of artemisone with cidofovir, brincidofovir, or with the HCMV UL97 inhibitor maribavir resulted in antiviral synergism and the combination of artemisone with ganciclovir or with the viral terminase inhibitors letermovir and BDCRB resulted in moderate synergism. Importantly, the combination of artemisone with maribavir demonstrated synergistic antiviral activity ex-vivo, in a clinically-relevant multicellular model of human placental tissues maintained in organ culture. Our findings provide the basis for the use of artemisone in synergistically acting drug combinations, to enhance viral control and reduce antiviral drug toxicities.

Topics: Acetates; Antiviral Agents; Artemisinins; Benzimidazoles; Cidofovir; Cytomegalovirus; Cytomegalovirus Infections; Cytosine; Drug Interactions; Drug Synergism; Drugs, Investigational; Female; Ganciclovir; Humans; Organ Culture Techniques; Organophosphonates; Placenta; Pregnancy; Quinazolines; Ribonucleosides

Human cytomegalovirus (HCMV) is a major cause of disease in immunocompromised individuals and the most common cause of congenital infection and neurosensorial disease. The expanding target populations for HCMV antiviral treatment along with the limitations of the currently available HCMV DNA polymerase inhibitors underscore the need for new antiviral agents with alternative modes of action. The antimalarial artemisinin derivative artesunate was shown to inhibit HCMV

Topics: Antiviral Agents; Artemisinins; Cell Line; Cytomegalovirus; Cytomegalovirus Infections; Fibroblasts; Ganciclovir; Humans; Microbial Sensitivity Tests; Virus Replication