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.
Highlights
Every year, emerging and re-emerging viruses, such as severe acute respiratory syndromeEvery emerging and re-emerging viruses, such as severe acute respiratory coronavirusyear,2 (SARS-CoV-2), MiddleEast respiratory syndrome (MERS-CoV), Zika virussyndrome (ZIKV), coronavirus (SARS-CoV-2), Zika surface virus (ZIKV), Ebola virus (EBOV), influenza A virus (FLUAV), and Rift Valley fever virus (RVFV) fromEbola virus (EBOV), A virusRift fever2020, virusthe (RVFV)surface from natural reservoirs to influenza infect, disable, and(FLUAV), kill peopleand [1,2].AsValley of October number of people natural to infect, continues disable, and kill people [1,2]
We have demonstrated that the combination of obatoclax and saliphenylhalamide is synergistic against ZIKV infection in retinal pigment epithelium (RPE) cells [6]
We have shown that combinations of nelfinavir with salinomycin, amodiaquine, obatoclax, emetine, and homoharringtonine all exhibit synergistic activity against SARS-CoV-2 in kidney epithelial cells extracted from an African green monkey (Vero-E6) [7]
Summary
Every year, emerging and re-emerging viruses, such as severe acute respiratory syndromeEvery emerging and re-emerging viruses, such as severe acute respiratory coronavirusyear,2 (SARS-CoV-2), MiddleEast respiratory syndrome (MERS-CoV), Zika virussyndrome (ZIKV), coronavirus (SARS-CoV-2), Zika surface virus (ZIKV), Ebola virus (EBOV), influenza A virus (FLUAV), and Rift Valley fever virus (RVFV) fromEbola virus (EBOV), A virusRift fever2020, virusthe (RVFV)surface from natural reservoirs to influenza infect, disable, and(FLUAV), kill peopleand [1,2].AsValley of October number of people natural to infect, continues disable, and kill people [1,2]. Every year, emerging and re-emerging viruses, such as severe acute respiratory syndrome. Every emerging and re-emerging viruses, such as severe acute respiratory coronavirusyear,. East respiratory syndrome (MERS-CoV), Zika virussyndrome (ZIKV), coronavirus (SARS-CoV-2), Zika surface virus (ZIKV), Ebola virus (EBOV), influenza A virus (FLUAV), and Rift Valley fever virus (RVFV) from. Surface from natural reservoirs to influenza infect, disable, and(FLUAV), kill peopleand [1,2]. AsValley of October number of people natural to infect, continues disable, and kill people [1,2]. As of October the1number infectedreservoirs with SARS-CoV-2 to rise, with a global death toll of more than million. SARS-CoV-2 continues to rise, with a global death toll of more than As of October the1number infectedreservoirs with SARS-CoV-2 to rise, with a global death toll of more than million. of people infected with
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