The antiviral activity of Isoprinosine

1972 ◽  
Vol 18 (9) ◽  
pp. 1463-1470 ◽  
Author(s):  
Paul Gordon ◽  
Eric R. Brown

A hypothesis predicting that increase in the rate of synthesis of host messenger RNA would be associated with antiviral activity was examined. Biochemically, Isoprinosine or NPT-10381 (methisoprinol) increased the rate of rapid labeling of polyribosomal RNA and protein in uninfected monkey kidney cells in tissue culture. In tissue-culture systems, Isoprinosine exerted antiviral effects against influenza virus, PR-8 and A2 strains; herpes virus, LU strain; polio virus 3; and adenovirus 10. In in vivo mortality studies, Isoprinosine was observed to exert therapeutic antiviral effects against the A2 strain of influenza and, as well, against a herpes infection of newborn mice. Experiments were carried out which demonstrated a correlation between the in vivo anti-influenza (PR-8) effects of Isoprinosine and reduction in the virus titer in lungs of infected mice.

1992 ◽  
Vol 3 (2) ◽  
pp. 107-112 ◽  
Author(s):  
D. Kinchington ◽  
J. J. Harvey ◽  
T. J. O'Connor ◽  
B. C. N. M. Jones ◽  
K. G. Devine ◽  
...  

A number of zidovudine phosphoramidate and phosphorodiamidate derivatives were prepared, including some previously unreported benzyl esterified amino acyl compounds. These were found to be active in vitro against the human immunodeficiency virus (HIV-1), and were tested subsequently in the S+L-tissue culture assay against urethane leukaemia virus (ULV), a murine leukaemia virus (MuLV). The fifteen compounds tested showed a similar range of activity against the two viruses. No active compounds were missed in the MuLV system which was usually more sensitive to antiviral effects. Five compounds showed some toxicity to the mouse cells only. We are using this system in parallel with HIV assays to identify those derivatives which will be tested subsequently against a murine retrovirus 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 ◽  
...  

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.


1959 ◽  
Vol 5 (5) ◽  
pp. 453-459 ◽  
Author(s):  
R. C. French ◽  
R. E. Armstrong ◽  
W. Yarosh

Under the conditions of the official Canadian test, it was found that two simultaneous first-order reactions were in competition. Thus, after 4 hours, while 15% of any initial live MEF1 poliovirus present was adsorbed to the monkey kidney cells, 9% of the virus was destroyed by spontaneous inactivation. When the adsorption rate was increased by decreasing the volume of fluid, it was found that significantly more isolations of virus were obtained. Utilizing the method of Baron for the concentration of polio virus it was found possible to maintain a low test volume without making the routine test unduly cumbersome. The modified test is simpler and more sensitive and may be used with undialyzed vaccines.


2020 ◽  
Author(s):  
Cui-Cui Li ◽  
Xiao-Jia Wang

Abstract Background: Porcine epidemic diarrhea virus (PEDV) of the family Coronaviridae has caused substantial economic losses in the swine husbandry industry. There’s currently no specific drug available for treatment of coronaviruses or PEDV. Method: In the current study, we use coronavirus PEDV as a model to study antiviral agents. Briefly, a fusion inhibitor tHR2, recombinant lentivirus-delivered shRNAs targeted to conserved M and N sequences, homoharringtonine (HHT), and hydroxychloroquine (HCQ) were surveyed for their antiviral effects. Results: Treatment with HCQ at 50 mM and HHT at 150 nM reduced virus titer in TCID50 by 30 and 3.5 fold respectively, and the combination reduced virus titer in TCID50 by 200 fold. Conclusion: Our report demonstrates that the combination of HHT and HCQ exhibited higher antiviral activity than either HHT or HCQ exhibited. The information may contribute to the development of antiviral strategies effective in controlling PEDV infection.


2020 ◽  
Vol 11 (4) ◽  
pp. 11172-11186

The challenges of SARS-CoV-2 have frightened the world due to a lack of effective treatment. Many clinicians have adopted drug repositioning because of the urgent need to contain the viral pandemic. Several studies have demonstrated the in vitro and in vivo antiviral efficacy of chloroquine and hydroxychloroquine in the treatment of SARS-CoV-2. However, the cardiovascular toxicity of chloroquine and hydroxychloroquine stand as a limitation to their general use to treat SARS-CoV-2. Thus, it is necessitated the search for an adjuvant that could be used alongside these treatments to mitigate the undesired effect. The cardioprotective activity of resveratrol could serve to mitigate the cardiovascular toxicity of chloroquine and hydroxychloroquine. Its antioxidant and anti-inflammatory properties synergistically with chloroquine or hydroxychloroquine could also mitigate the antiviral activity of SARS-CoV-2. In this review, we explore chloroquine and hydroxychloroquine for SARS-CoV-2 treatment and suggest their synergetic use with resveratrol as a recommended therapy to mitigate cardiovascular toxicity and contribute to their antiviral effects.


1960 ◽  
Vol XXXIII (II) ◽  
pp. 277-286 ◽  
Author(s):  
Weiert Velle ◽  
Stian Erichsen

ABSTRACT A review is given of previous in vitro investigations on oestrogen metabolism. In the present investigation use has been made of the tissue culture technique, whereby possible blood or serum effects on oestrogen transformations could be excluded. The conversion products were characterized by chemical methods. In the presence of bovine kidney cells grown on a medium of known composition, the following conversions were recorded: Oestrone to oestradiol-17β, oestradiol-17β to oestrone, oestradiol-17α to oestrone. Control incubations of the hormones with medium only showed that the transformations must be due to the presence of the living cells. The rate of conversion to oestrone was markedly higher for oestradiol-17β than for oestradiol-17α. As previous in vivo experiments have shown oestradiol-17α to be an important end product in the bovine, following injections of both oestrone and oestradiol-17β, the free interconvertibility of oestrone and oestradiol-17β demonstrated in the present investigation becomes significant. The findings are discussed in relation to recent observations on hormoneenzyme interrelations.


1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S369-S380 ◽  
Author(s):  
Francis T. Kenney ◽  
Kai-Lin Lee ◽  
Charles D. Stiles

ABSTRACT Analyses of the response of hydrocortisone-induced tyrosine transaminase in cultured H-35 cells to inhibitors of translation (cycloheximide, puromycin) suggest: (1) that bound ribosomes stabilize messenger RNA in vivo; (2) that messenger is degraded at a rate determined by the rate of translation. Since specific messenger RNAs of mammalian cells are degraded at quite different rates, there may be extensive heterogeneity either in the rate at which ribosomes traverse different messengers or in the number of ribosomes which translate specific messenger RNAs.


1980 ◽  
Vol 45 (8) ◽  
pp. 2364-2370 ◽  
Author(s):  
Antonín Holý ◽  
Erik De Clercq

Reaction of 3',5'-di-O-benzoyl-6-methyl-2'-deoxyuridine (IIa) with elementary bromine or iodine afforded 5-halogeno derivatives IIc and IId which on methanolysis gave 5-bromo-6-methyl-2'-deoxyurine (Ic) and 5-iodo-6-methyl-2'-deoxyurine (Id), respectively. The CD spectra of Ic, Id and 6-methyl-2'-deoxyuridine (Ia) are compared and discussed with regard to determination of the nucleoside conformation. Unlike 5-bromo- and 5-iodo-2'-deoxyuridine, the 6-methyl derivatives Ic and Id exhibit neither antibacterial nor antiviral activity. Nor do they exert any antimetabolic effect on the de novo DNA synthesis in primary rabbit kidney cells.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 308
Author(s):  
Ying-Ray Lee ◽  
Chia-Ming Chang ◽  
Yuan-Chieh Yeh ◽  
Chi-Ying F. Huang ◽  
Feng-Mao Lin ◽  
...  

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.


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