scholarly journals Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction

Cell Research ◽  
2017 ◽  
Vol 27 (8) ◽  
pp. 1046-1064 ◽  
Author(s):  
Zhong Li ◽  
Matthew Brecher ◽  
Yong-Qiang Deng ◽  
Jing Zhang ◽  
Srilatha Sakamuru ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus

scholarly journals Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 774
Author(s):  
Chengfeng Gao ◽  
Chunxia Wen ◽  
Zhifeng Li ◽  
Shuhan Lin ◽  
Shu Gao ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus ◽  
Therapeutic Agent ◽  
Viral Infections ◽  
Rna Virus ◽  
Emerging Viruses ◽  
Enterovirus A71 ◽  
Ic50 Values ◽  
High Doses ◽  
Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

scholarly journals Efficacy of the broad-spectrum antiviral compound BCX4430 against Zika virus in cell culture and in a mouse model

2017 ◽  
Vol 137 ◽  
pp. 14-22 ◽  
Author(s):  
Justin G. Julander ◽  
Venkatraman Siddharthan ◽  
Joe Evans ◽  
Ray Taylor ◽  
Kelsey Tolbert ◽  
...  
Keyword(s):  
Cell Culture ◽  
Mouse Model ◽  
Broad Spectrum ◽  
Zika Virus ◽  
Antiviral Compound

scholarly journals Labyrinthopeptins Exert Broad-Spectrum Antiviral Activity through Lipid-Binding-Mediated Virolysis

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Hans Prochnow ◽  
Katharina Rox ◽  
N. V. Suryanarayana Birudukota ◽  
Loreen Weichert ◽  
Sven-Kevin Hotop ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Host Cell ◽  
Broad Spectrum ◽  
Zika Virus ◽  
Kaposi's Sarcoma ◽  
Chikungunya Virus ◽  
Viral Infections ◽  
Kaposi’S Sarcoma ◽  
Membrane Lipid ◽  
Virus Zika

ABSTRACT To counteract the serious health threat posed by known and novel viral pathogens, drugs that target a variety of viruses through a common mechanism have attracted recent attention due to their potential in treating (re)emerging infections, for which direct-acting antivirals are not available. We found that labyrinthopeptins A1 and A2, the prototype congeners of carbacyclic lanthipeptides, inhibit the proliferation of diverse enveloped viruses, including dengue virus, Zika virus, West Nile virus, hepatitis C virus, chikungunya virus, Kaposi’s sarcoma-associated herpesvirus, cytomegalovirus, and herpes simplex virus, in the low micromolar to nanomolar range. Mechanistic studies on viral particles revealed that labyrinthopeptins induce a virolytic effect through binding to the viral membrane lipid phosphatidylethanolamine (PE). These effects are enhanced by a combined equimolar application of both labyrinthopeptins, and a clear synergism was observed across a concentration range corresponding to 10% to 90% inhibitory concentrations of the compounds. Time-resolved experiments with large unilamellar vesicles (LUVs) reveal that membrane lipid raft compositions (phosphatidylcholine [PC]/PE/cholesterol/sphingomyelin at 17:10:33:40) are particularly sensitive to labyrinthopeptins in comparison to PC/PE (90:10) LUVs, even though the overall PE amount remains constant. Labyrinthopeptins exhibited low cytotoxicity and had favorable pharmacokinetic properties in mice (half-life [t1/2] = 10.0 h), which designates them promising antiviral compounds acting by an unusual viral lipid targeting mechanism. IMPORTANCE For many viral infections, current treatment options are insufficient. Because the development of each antiviral drug is time-consuming and expensive, the prospect of finding broad-spectrum antivirals that can fight multiple, diverse viruses—well-known viruses as well as (re)emerging species—has gained attention, especially for the treatment of viral coinfections. While most known broad-spectrum agents address processes in the host cell, we found that targeting lipids of the free virus outside the host cell with the natural products labyrinthopeptin A1 and A2 is a viable strategy to inhibit the proliferation of a broad range of viruses from different families, including chikungunya virus, dengue virus, Zika virus, Kaposi’s sarcoma-associated herpesvirus, and cytomegalovirus. Labyrinthopeptins bind to viral phosphatidylethanolamine and induce virolysis without exerting cytotoxicity on host cells. This represents a novel and unusual mechanism to tackle medically relevant viral infections.

scholarly journals Methylene blue is a potent and broad-spectrum inhibitor against Zika virus in vitro and in vivo

2020 ◽  
Vol 9 (1) ◽  
pp. 2404-2416
Author(s):  
Zhong Li ◽  
Yuekun Lang ◽  
Srilatha Sakamuru ◽  
Subodh Samrat ◽  
Nicole Trudeau ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Broad Spectrum ◽  
Zika Virus

scholarly journals Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus

Cell Reports ◽  
2017 ◽  
Vol 18 (3) ◽  
pp. 804-815 ◽  
Author(s):  
Keiko Rausch ◽  
Brent A. Hackett ◽  
Nathan L. Weinbren ◽  
Sophia M. Reeder ◽  
Yoel Sadovsky ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus

scholarly journals Identification of Broad-Spectrum Dengue/Zika Virus Replication Inhibitors by Functionalization of Quinoline and 2,6-Diaminopurine Scaffolds

ChemMedChem ◽  
2018 ◽  
Vol 13 (14) ◽  
pp. 1371-1376 ◽  
Author(s):  
Suzanne J. F. Kaptein ◽  
Paolo Vincetti ◽  
Emmanuele Crespan ◽  
Jorge I. Armijos Rivera ◽  
Gabriele Costantino ◽  
...  
Keyword(s):  
Virus Replication ◽  
Broad Spectrum ◽  
Zika Virus

scholarly journals Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus

EBioMedicine ◽  
2019 ◽  
Vol 47 ◽  
pp. 269-283 ◽  
Author(s):  
Alicia Martinez-Lopez ◽  
Mirjana Persaud ◽  
Maritza Puray Chavez ◽  
Hongjie Zhang ◽  
Lijun Rong ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus ◽  
Antiviral Agent

scholarly journals Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1019 ◽  
Author(s):  
Gao ◽  
Tai ◽  
Wang ◽  
Li ◽  
Jiang ◽  
...  
Keyword(s):  
Natural Products ◽  
Broad Spectrum ◽  
Zika Virus ◽  
The Other ◽  
Protein Domain ◽  
Mechanistic Study ◽  
Zikv Infection ◽  
Domain Iii ◽  
Almost All

Zika virus (ZIKV) infection during pregnancy leads to severe congenital Zika syndrome, which includes microcephaly and other neurological malformations. No therapeutic agents have, so far, been approved for the treatment of ZIKV infection in humans; as such, there is a need for a continuous effort to develop effective and safe antiviral drugs to treat ZIKV-caused diseases. After screening a natural product library, we have herein identified four natural products with anti-ZIKV activity in Vero E6 cells, including gossypol, curcumin, digitonin, and conessine. Except for curcumin, the other three natural products have not been reported before to have anti-ZIKV activity. Among them, gossypol exhibited the strongest inhibitory activity against almost all 10 ZIKV strains tested, including six recent epidemic human strains. The mechanistic study indicated that gossypol could neutralize ZIKV infection by targeting the envelope protein domain III (EDIII) of ZIKV. In contrast, the other natural products inhibited ZIKV infection by targeting the host cell or cell-associated entry and replication stages of ZIKV. A combination of gossypol with any of the three natural products identified in this study, as well as with bortezomib, a previously reported anti-ZIKV compound, exhibited significant combinatorial inhibitory effects against three ZIKV human strains tested. Importantly, gossypol also demonstrated marked potency against all four serotypes of dengue virus (DENV) human strains in vitro. Taken together, this study indicates the potential for further development of these natural products, particularly gossypol, as the lead compound or broad-spectrum inhibitors against ZIKV and other flaviviruses, such as DENV.

scholarly journals Cover Feature: Identification of Broad-Spectrum Dengue/Zika Virus Replication Inhibitors by Functionalization of Quinoline and 2,6-Diaminopurine Scaffolds (ChemMedChem 14/2018)

ChemMedChem ◽  
2018 ◽  
Vol 13 (14) ◽  
pp. 1370-1370
Author(s):  
Suzanne J. F. Kaptein ◽  
Paolo Vincetti ◽  
Emmanuele Crespan ◽  
Jorge I. Armijos Rivera ◽  
Gabriele Costantino ◽  
...  
Keyword(s):  
Virus Replication ◽  
Broad Spectrum ◽  
Zika Virus ◽  
Feature Identification
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