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      Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms

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          Abstract

          Mosquito-borne Zika virus (ZIKV) is a Flavivirus that came under intense study from 2014 to 2016 for its well-known ability to cause congenital microcephaly in fetuses and neurological Guillain–Barré disease in adults. Substantial research on screening antiviral agents against ZIKV and preventing ZIKV infection are globally underway, but Food and Drug Administration (FDA)-approved treatments are not available yet. Compounds from Chinese medicinal herbs may offer an opportunity for potential therapies for anti-ZIKV infection. In this study, we evaluated the antiviral efficacy of harringtonine against ZIKV. Harringtonine possessed anti-ZIKV properties against the binding, entry, replication, and release stage through the virus life cycle. In addition, harringtonine have strong virucidal effects in ZIKV and exhibited prophylaxis antiviral ability prior ZIKV infection. The antiviral activity also observed in the treatment against Japanese encephalitis reporter virus (RP9-GFP strain). Overall, this study demonstrated that harringtonine would be a favorable potential candidate for the development of anti-ZIKV infection therapies.

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

          Ka-Tim Choy, Alvina Yin-Lam Wong, Prathanporn Kaewpreedee … (2020)
          An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.
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            PatchDock and SymmDock: servers for rigid and symmetric docking

            Dina Schneidman-Duhovny, Yuval Inbar, Ruth Nussinov … (2005)
            Here, we describe two freely available web servers for molecular docking. The PatchDock method performs structure prediction of protein–protein and protein–small molecule complexes. The SymmDock method predicts the structure of a homomultimer with cyclic symmetry given the structure of the monomeric unit. The inputs to the servers are either protein PDB codes or uploaded protein structures. The services are available at . The methods behind the servers are very efficient, allowing large-scale docking experiments.
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              Zika virus outbreak on Yap Island, Federated States of Micronesia.

              Mark Duffy, Tai-Ho Chen, W. Thane Hancock … (2009)
              In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission. 2009 Massachusetts Medical Society
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                Author and article information

                Contributors
                Justin Jang Hann Chu: Role: Academic Editor
                Chee Keng Mok: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 07 September 2020
                Publication date Collection: September 2020
                Volume: 25
                Issue: 18
                Electronic Location Identifier: 4082
                Affiliations
                [1 ]Department and Graduate Institute of Pharmacology, National Defense Medical Center, Taipei 114, Taiwan; laizengzong@ 123456gmail.com
                [2 ]Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
                [3 ]Graduate Institute of Medical Science, National Defense Medical Center, Taipei 114, Taiwan
                [4 ]School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan
                [5 ]Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan
                [6 ]Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
                Author notes
                [* ]Correspondence: ejung330@ 123456gmail.com (Y.-J.H.); jengweilu@ 123456gmail.com (J.-W.L.); Tel.: +886-2-87923100 (ext. 18886) (Y.-J.H.); +65-6516-8940 (J.-W.L.)
                Author information
                https://orcid.org/0000-0003-2128-2046
                Article
                Publisher ID: molecules-25-04082
                DOI: 10.3390/molecules25184082
                PMC ID: 7570876
                PubMed ID: 32906689
                SO-VID: bb21ff19-a415-43b1-baea-4e0238d90d09
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 14 August 2020
                Date accepted : 06 September 2020
                Categories
                Subject: Article

                Keywords: antiviral,harringtonine,binding,entry,replication,zika virus
                Data availability:
                Keywords: antiviral, harringtonine, binding, entry, replication, zika virus

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