1. Academic Validation
  2. Identification and Tracking of Antiviral Drug Combinations

Identification and Tracking of Antiviral Drug Combinations

  • Viruses. 2020 Oct 18;12(10):1178. doi: 10.3390/v12101178.
Aleksandr Ianevski 1 Rouan Yao 1 Svetlana Biza 1 Eva Zusinaite 2 Andres Mannik 3 Gaily Kivi 3 Anu Planken 3 Kristiina Kurg 3 Eva-Maria Tombak 3 Mart Ustav Jr 3 Nastassia Shtaida 2 Evgeny Kulesskiy 4 Eunji Jo 5 Jaewon Yang 5 Hilde Lysvand 1 Kirsti Løseth 1 Valentyn Oksenych 1 Per Arne Aas 1 Tanel Tenson 2 Astra Vitkauskienė 6 Marc P Windisch 5 Mona Høysæter Fenstad 1 7 Svein Arne Nordbø 1 8 Mart Ustav 3 Magnar Bjørås 1 Denis E Kainov 1 2 4
Affiliations

Affiliations

  • 1 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7028 Trondheim, Norway.
  • 2 Institute of Technology, University of Tartu, 50090 Tartu, Estonia.
  • 3 Icosagen Cell Factory OÜ, 61713 Kambja vald Tartumaa, Estonia.
  • 4 Institute for Molecular Medicine Finland, FIMM, University of Helsinki, 00014 Helsinki, Finland.
  • 5 Applied Molecular Virology Laboratory, Institut Pasteur Korea, Sampyeong-dong 696, Bundang-gu, Seongnam-si 463-400, Gyeonggi-do, Korea.
  • 6 Department of Laboratory Medicine, Lithuanian University of Health Science, 44307 Kaunas, Lithuania.
  • 7 Department of Medical Microbiology, St. Olavs Hospital, 7006 Trondheim, Norway.
  • 8 Department of Immunology and Transfusion Medicine, St. Olavs Hospital, 7006 Trondheim, Norway.
Abstract

Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. We observed synergistic activity of nelfinavir with convalescent serum and with purified neutralizing antibody 23G7 against SARS-CoV-2 in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of nelfinavir with EIDD-2801 or remdesivir in Calu-3 cells. In addition, we showed synergistic activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 Infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV Infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 Infection in human cervical TZM-bl cells. These results indicate that synergy is achieved when a virus-directed Antiviral is combined with another virus- or host-directed agent. Finally, we present an online resource that summarizes novel and known Antiviral drug combinations and their developmental status.

Keywords

antiviral drug combinations; antivirals; broad-spectrum antivirals; virus.

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