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Identification and Tracking of Antiviral Drug Combinations

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
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Applied Molecular Virology Laboratory, Institut Pasteur Korea, Sampyeong-dong 696, Bundang-gu, Seongnam-si 463-400, Gyeonggi-do, Korea
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Department of Laboratory Medicine, Lithuanian University of Health Science, 44307 Kaunas, Lithuania
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Department of Medical Microbiology, St. Olavs Hospital, 7006 Trondheim, Norway
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Department of Immunology and Transfusion Medicine, St. Olavs Hospital, 7006 Trondheim, Norway
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(10), 1178; https://doi.org/10.3390/v12101178
Received: 22 September 2020 / Revised: 14 October 2020 / Accepted: 15 October 2020 / Published: 18 October 2020
(This article belongs to the Special Issue Antiviral Drug Combinations)
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. View Full-Text
Keywords: antivirals; antiviral drug combinations; broad-spectrum antivirals; virus antivirals; antiviral drug combinations; broad-spectrum antivirals; virus
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Ianevski, A.; Yao, R.; Biza, S.; Zusinaite, E.; Mannik, A.; Kivi, G.; Planken, A.; Kurg, K.; Tombak, E.-M.; Ustav, M., Jr.; Shtaida, N.; Kulesskiy, E.; Jo, E.; Yang, J.; Lysvand, H.; Løseth, K.; Oksenych, V.; Aas, P.A.; Tenson, T.; Vitkauskienė, A.; Windisch, M.P.; Fenstad, M.H.; Nordbø, S.A.; Ustav, M.; Bjørås, M.; Kainov, D.E. Identification and Tracking of Antiviral Drug Combinations. Viruses 2020, 12, 1178.

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