Identification and Tracking of Antiviral Drug Combinations

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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 , Shtaida , N , Kulesskiy , E , Jo , E , Yang , J , Lysvand , H , Loseth , K , Oksenych , V , Aas , P A , Tenson , T , Vitkauskiene , A , Windisch , M P , Fenstad , M H , Nordbo , S A , Ustav , M , Bjoras , M & Kainov , D E 2020 , ' Identification and Tracking of Antiviral Drug Combinations ' , Viruses-Basel , vol. 12 , no. 10 , 1178 .

Title: Identification and Tracking of Antiviral Drug Combinations
Author: Ianevski, Aleksandr; Yao, Rouan; Biza, Svetlana; Zusinaite, Eva; Mannik, Andres; Kivi, Gaily; Planken, Anu; Kurg, Kristiina; Tombak, Eva-Maria; Ustav, Mart; Shtaida, Nastassia; Kulesskiy, Evgeny; Jo, Eunji; Yang, Jaewon; Lysvand, Hilde; Loseth, Kirsti; Oksenych, Valentyn; Aas, Per Arne; Tenson, Tanel; Vitkauskiene, Astra; Windisch, Marc P.; Fenstad, Mona Hoysaeter; Nordbo, Svein Arne; Ustav, Mart; Bjoras, Magnar; Kainov, Denis E.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2020-10
Language: eng
Number of pages: 15
Belongs to series: Viruses-Basel
ISSN: 1999-4915
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.
Subject: antivirals
antiviral drug combinations
broad-spectrum antivirals
11832 Microbiology and virology

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