scholarly journals The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 601 ◽  
Author(s):  
Hui-Jun Dong ◽  
Zhao-Hua Wang ◽  
Wen Meng ◽  
Cui-Cui Li ◽  
Yan-Xin Hu ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Messenger Rna ◽  
Initiation Factor ◽  
Diarrhea Virus ◽  
Eukaryotic Initiation Factor 4E ◽  
Starting Point ◽  
Selective Translation ◽  
Simplex Virus

To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively. Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals. HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses. In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC50) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude. Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA). HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals.

scholarly journals Phosphorylation of eukaryotic initiation factor 4E (eIF4E) at Ser209 is not required for protein synthesis in vitro and in vivo

2001 ◽  
Vol 268 (20) ◽  
pp. 5375-5385 ◽  
Author(s):  
Linda McKendrick ◽  
Simon J. Morley ◽  
Virginia M. Pain ◽  
Rosemary Jagus ◽  
Bhavesh Joshi
Keyword(s):  
Protein Synthesis ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 4E

scholarly journals Antiviral activity of PHA767491 against human herpes simplex virus in vitro and in vivo

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Jue Hou ◽  
Zili Zhang ◽  
Qiang Huang ◽  
Jun Yan ◽  
Xiaohu Zhang ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Human Herpes ◽  
Simplex Virus

Antiherpesvirus Activity of the Combination of 5-iodo-2′-deoxycytidine with methotrexate: An in vitro and in vivo Study

1994 ◽  
Vol 5 (5) ◽  
pp. 283-289
Author(s):  
C. Cremonesi ◽  
C. Scarpini ◽  
R. Bianchi ◽  
A. Radaelli ◽  
M. Gimelli ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dihydrofolate Reductase ◽  
Reductase Inhibitor ◽  
Cellular Viability ◽  
Cutaneous Lesions ◽  
Guinea Pig Model ◽  
Simplex Virus ◽  
Hsv 1

We evaluated the in vitro and in vivo antiviral activity of the deoxyribonucleoside analogue 5-iodo-2′-deoxycytidine (IDC) combined with the dihydrofolate reductase inhibitor methotrexate (MTX) on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). The IDC-MTX combination synergistically inhibited HSV-1 and HSV-2 replication in vitro at concentrations that did not reduce cellular viability and was very effective in reducing the severity of cutaneous lesions in the experimental guinea pig model in vivo. The antiviral activity of the IDC-MTX combination in guinea pigs was also compared with that of acyclovir and was demonstrated to be higher.

scholarly journals Amphipathic DNA Polymers Exhibit Antiherpetic Activity In Vitro and In Vivo

2008 ◽  
Vol 52 (8) ◽  
pp. 2727-2733 ◽  
Author(s):  
David I. Bernstein ◽  
Nathalie Goyette ◽  
Rhonda Cardin ◽  
Earl R. Kern ◽  
Guy Boivin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Parent Compound ◽  
Human Herpesvirus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Simplex Virus ◽  
Acid Stable

ABSTRACT Phosphorothioated oligonucleotides have a sequence-independent antiviral activity as amphipathic polymers (APs). The activity of these agents against herpesvirus infections in vitro and in vivo was investigated. The previously established sequence-independent, phosphorothioation-dependent antiviral activity of APs was confirmed in vitro by showing that a variety of equivalently sized homo- and heteropolymeric AP sequences were similarly active against herpes simplex virus type 1 (HSV-1) infection in vitro compared to the 40mer degenerate parent compound (REP 9), while the absence of phosphorothioation resulted in the loss of antiviral activity. In addition, REP 9 demonstrated in vitro activity against a broad spectrum of other herpesviruses: HSV-2 (50% effective concentration [EC50], 0.02 to 0.06 μM), human cytomegalovirus (EC50, 0.02 to 0.13 μM), varicella zoster virus (EC50, <0.02 μM), Epstein-Barr virus (EC50, 14.7 μM) and human herpesvirus types 6A/B (EC50, 2.9 to 10.2 μM). The murine microbicide model of genital HSV-2 was then used to evaluate in vivo activity. REP 9 (275 mg/ml) protected 75% of animals from disease and infection when provided 5 or 30 min prior to vaginal challenge. When an acid-stable analog (REP 9C) was used, 75% of mice were protected when treated with 240 mg/ml 5 min prior to infection (P < 0.001), while a lower dose (100 mg/ml) protected 100% of the mice (P < 0.001). The acid stable REP 9C formulation also provided protection at 30 min (83%, P < 0.001) and 60 min (50%, P = 0.07) against disease. These observations suggest that APs may have microbicidal activity and potential as broad-spectrum antiherpetic agents and represent a novel class of agents that should be studied further.

scholarly journals Potent In Vivo Antiviral Activity of the Herpes Simplex Virus Primase-Helicase Inhibitor BAY 57-1293

2002 ◽  
Vol 46 (6) ◽  
pp. 1766-1772 ◽  
Author(s):  
Ulrich A. K. Betz ◽  
Rüdiger Fischer ◽  
Gerald Kleymann ◽  
Martin Hendrix ◽  
Helga Rübsamen-Waigmann
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Lethal Challenge ◽  
Antiviral Compounds ◽  
Ocular Herpes ◽  
Spread Model ◽  
Simplex Virus

ABSTRACT BAY 57-1293 belongs to a new class of antiviral compounds and inhibits replication of herpes simplex virus (HSV) type 1 and type 2 in the nanomolar range in vitro by abrogating the enzymatic activity of the viral primase-helicase complex. In various rodent models of HSV infection the antiviral activity of BAY 57-1293 in vivo was found to be superior compared to all compounds currently used to treat HSV infections. The compound shows profound antiviral activity in murine and rat lethal challenge models of disseminated herpes, in a murine zosteriform spread model of cutaneous disease, and in a murine ocular herpes model. It is active in parenteral, oral, and topical formulations. BAY 57-1293 continued to demonstrate efficacy when the onset of treatment was initiated after symptoms of herpetic disease were already apparent.

scholarly journals Dendrimers, a New Class of Candidate Topical Microbicides with Activity against Herpes Simplex Virus Infection

2000 ◽  
Vol 44 (9) ◽  
pp. 2471-2474 ◽  
Author(s):  
N. Bourne ◽  
L. R. Stanberry ◽  
E. R. Kern ◽  
G. Holan ◽  
B. Matthews ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Rectal Mucosa ◽  
Biological Properties ◽  
Sexually Transmitted ◽  
Topical Microbicides ◽  
Simplex Virus

ABSTRACT Dendrimers are large highly branched macromolecules synthesized from a polyfunctional core. They have shown a variety of biological properties, including, in some instances, antiviral activity. In this study, five dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) types 1 and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in human foreskin fibroblast cells. All of the compounds were active against both virus types in the CPE inhibition assay, in which drug was added to the cells prior to the addition of virus. Antiviral activity was reduced or lost in the PR assays, in which the cells were incubated with the virus before the drug was added. The prophylactic efficacy suggested that the dendrimers might have potential as topical microbicides, products intended to be applied to the vaginal or rectal mucosa to protect against sexually transmitted infections. Three dendrimers were evaluated for this application against genital HSV infection in mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced infection rates when 15 μl of a 100-mg/ml solution was administered immediately prior to intravaginal challenge, and the most effective compound, BRI-2999, provided significant protection even when applied 30 min before challenge. This is the first report of microbicidal activity by dendrimers in vivo.

scholarly journals Cordia americana: Evaluation of in vitro anti-herpes simplex virus activity and in vivo toxicity of leaf extracts

2021 ◽  
pp. 362-368
Author(s):  
Gislaine Franco de Moura- Costa ◽  
Gean Pier Panizzon ◽  
Thalita Zago Oliveira ◽  
Marco Antonio Costa ◽  
João Carlos Palazzo de Mello ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Biological Activities ◽  
Leaf Extracts ◽  
In Vivo Toxicity ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections

Antisense strategies and therapeutic applications

1996 ◽  
Vol 53 (2) ◽  
pp. 151-160 ◽  
Author(s):  
Putnam David A.
Keyword(s):  
Virus Infection ◽  
Messenger Rna ◽  
Therapeutic Agents ◽  
Water Soluble ◽  
Rna Sequences ◽  
Potential Applications ◽  
Antisense Approach ◽  
Simplex Virus

The concepts underlying the antisense approach to disease therapy are discussed, and potential applications are examined. Antisense therapeutic agents bind to DNA or RNA sequences, biocking the synthesis of cellular proteins with unparalleled specificity. Transcription and translation are the two processes with which the agents interfere. There are three major classes of antisense agents: antisense sequences, commonly called antisense oligonucleotides; antigene sequences; and ribozymes. Antisense sequences are derivatives of nucleic acids that hybridize cytosolic messenger RNA (mRNA) sense strands through hydrogen bonding to complementary nucleic acid bases. Antigene sequences hybridize double-stranded DNA in the nucleus, forming triple helixes. Ribozymes, rather than inhibiting protein synthesis simply by binding to a single targeted mRNA. combine enzymatic processes with the specificity of antisense Iwse pairing, creating a molecule that can incapacitate multiple targeted niRNAs. Anti-sense therapeutic agents are being investigated in vitro and in vivo for use in treating human immunodeficiency virus infection, hepatitis B virus infection, herpes simplex virus infection, papillomavirus infection, cancer, restenosis, rheumatoid arthritis, and allergic disorders. Although many results are preliminary, some are promising and has e led to clinical trials. A major goal in developing methods of delivering antisense agents is to reduce their susceptibility to nucleases while retaining their ability to bind to targeted sites. Modification of the phosphodiester linkages in oligonucleotides can lend the sequences enzymatic stability without affecting their binding capacities. Carrier systems designed to protect the antisense structure and improve passage through the cell membrane include liposomes, water-soluble polyrners, and nanoparticles. The pharmacokinetics of anti-sense agents are under investigation. Antisense therapeutic agents have the potential to become an integral part of medicinal regimens.

Antiviral activity of arbidol hydrochloride against herpes simplex virus I in vitro and in vivo

2018 ◽  
Vol 51 (1) ◽  
pp. 98-106 ◽  
Author(s):  
Min-ke Li ◽  
Yuan-yuan Liu ◽  
Fei Wei ◽  
Meng-xin Shen ◽  
Yan Zhong ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Simplex Virus
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