2. Academic Validation
  3. Artemisone demonstrates synergistic antiviral activity in combination with approved and experimental drugs active against human cytomegalovirus

Artemisone demonstrates synergistic antiviral activity in combination with approved and experimental drugs active against human cytomegalovirus

  • Antiviral Res. 2019 Dec;172:104639. doi: 10.1016/j.antiviral.2019.104639.
Esther Oiknine-Djian 1,  Shikma Bar-On 2,  Ido Laskov 2,  Daniel Lantsberg 2,  Richard K Haynes 3,  Amos Panet 4,  Dana G Wolf 5
Affiliations

Affiliations

  • 1 Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel; The Lautenberg Center for General and Tumor Immunology, IMRIC, The Hebrew University, Israel.
  • 2 Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 3 Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
  • 4 Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
  • 5 Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; The Lautenberg Center for General and Tumor Immunology, IMRIC, The Hebrew University, Israel. Electronic address: dana.wolf@ekmd.huji.ac.il.
PMID: 31654672 DOI: 10.1016/j.antiviral.2019.104639
Abstract

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.

Keywords

Antiviral drug combinations; Antiviral drugs; Artemisone; Human cytomegalovirus.

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