Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

Abstract

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.

Tilorone: a Broad-Spectrum Antiviral Invented in the USA and Commercialized in Russia and beyond

“…A further role may be via its lysosomotropic activity which could impact viral entry. Antiviral Activity EBOV: viral replication EC 50 Tablets supplied in a single dosage strength and packaged for maximal stability in high-humidity and warm temperature environments.…”

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

“…Omacetaxine, a semi-synthetic form of homoharringtonine, is approved by FDA for treatment of chronic myeloid leukemia. Homoharringtonine has also been reported to exhibit potent anti-viral activity against herpesviruses (varicella-zoster virus, herpes simplex virus-1, pseudorabies virus), coronaviruses (porcine epidemic diarrhea virus and murine hepatitis virus), rhabdoviruses (VSV and rabies virus), and other viruses (hepatitis B virus, Newcastle disease virus, and echovirus 1) (Dong et al, 2018;Andersen et al, 2019). Here, we observed homoharringtonine inhibits SARS-CoV-2 with EC 50 at 2.10 μM (Fig.…”

“…However, its potential cardiotoxicity has restricted its clinical use in the recent years. It was found to process antiviral activity against a broad range of RNA and DNA viruses, including Zika virus, Ebolavirus, Cytomegalovirus, rabies virus, HIV-1, echovirus 1, buffalo poxvirus, bovine herpesvirus 1, peste des petits ruminants virus, Newcastle disease virus, herpes simplex virus-2, metapneumovirus, Rift Valley fever virus, and influenza (Andersen et al, 2019;Chaves Valadao et al, 2015;Khandelwal et al, 2017;MacGibeny et al, 2018;Mukhopadhyay et al, 2016;Yang et al, 2018). Emetine was also identified to inhibit hCoV-OC43, hCoV-NL43, SARS-CoV, MERS-CoV, and MHV-A59 in vitro with EC 50 reported at low micromolar range (Dyall et al, 2014;Shen et al, 2019).…”

Discovery and development of safe-in-man broad-spectrum antiviral agents

“…For example, TZM-bl cells expressing firefly luciferase under control of HIV-1 LTR promoter allowed quantitation of BSAA action on HIV-1 infection (tat-protein expression by integrated HIV-1 provirus) using firefly luciferase assay (Sarzotti-Kelsoe et al, 2014;Xing et al, 2016). RFPexpressing RVFV, nanoLuc-expressing CHIKV and RRV, as well as GFP-expressing FLUAV, HCV and HMPV also allowed identification of novel activities of several BSAAs (Andersen et al, 2019b;Bosl et al, 2019;de Graaf et al, 2007;Habjan et al, 2008;Ianevski et al, 2018;Jupille et al, 2011;Kittel et al, 2004;Lee et al, 2017;Utt et al., 2016). In addition, qPCR/RT-qPCR, RNA/DNA sequencing, RNA/DNA hybridization, immuno-and plaque assays as well as CRISPR-CAS9 systems could be used for detection of inhibitory effects of BSAAs (Boonham et al, 2014;Fischer et al, 2017;Konig et al, 2019;Laamiri et al, 2018;Landry, 1990;Perez et al, 2013;Sashital, 2018;Zhou et al, 2018).…”

“…Novel anti-HSV-2 and anti-EV1 activities of emetine were discovered recently using CTG/plaque assays in human non-malignant RPE cells. Moreover, novel antiviral activities of the drug were identified using RFP-expressing RVFV, and GFP-expressing HMPV or FLUAV strains in RPE cells (Andersen et al, 2019a).…”