Antiviral activity of uridine 5′-diphosphate glucose analogues against some enveloped viruses in cell culture

Introduction. The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen.The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus.Material and methods. The experiments had been carried out on Vero Cl008, the continuous line of African green monkey (Chlorocebus sabaeus) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro. The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies.Results. The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 102–106 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated.Discussion. IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (>1000).Conclusion. Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.

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Nanodroplet-Benzalkonium Chloride Formulation Demonstrates In Vitro and Ex- Vivo Broad-Spectrum Antiviral Activity Against SARS-CoV-2 and other Enveloped Viruses

10.21203/rs.3.rs-362864/v1 ◽

2021 ◽

Author(s):

Jessie Pannu ◽

Susan Ciotti ◽

Shyamala Ganesan ◽

George Arida ◽

Chad Costley ◽

...

Keyword(s):

Antiviral Activity ◽

Broad Spectrum ◽

Benzalkonium Chloride ◽

Ex Vivo ◽

Viral Disease ◽

Influenza B ◽

Human Coronavirus ◽

Enveloped Viruses ◽

Nasal Irritation

Abstract Objective: The Covid-19 pandemic has highlighted the importance of aerosolized droplets inhaled into the nose in the transmission of respiratory viral disease. Inactivating pathogenic viruses at the nasal port of entry may reduce viral loads, thereby reducing infection, transmission and spread. In this communication, we demonstrate safe and broad anti-viral activity of oil-in-water nanoemulsion (nanodroplet) formulation containing the potent antiseptic 0.13% Benzalkonium Chloride (NE-BZK). Results: We have demonstrated that NE-BZK exhibits broad-spectrum, long-lasting antiviral activity with >99.9% in vitro killing of enveloped viruses including SARS-CoV-2, human coronavirus, RSV, and influenza B. In vitro and ex-vivo studies demonstrated continued killing of >99.99% of human coronavirus with diluted NE-BZK and persistent for 8 hours post application, respectively. The repeated application of NE-BZK, twice daily for 2 weeks into rabbit nostrils demonstrated its safety with no nasal irritation. These findings demonstrate that formulating BZK into the proprietary nanodroplets offers a safe and effective antiviral and a significant addition to strategies to combat the spread of respiratory viral infectious diseases.

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Inhibition of human cytomegalovirus immediate-early gene expression by an antisense oligonucleotide complementary to immediate-early RNA.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2004 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2004-2011 ◽

Cited By ~ 97

Author(s):

K P Anderson ◽

M C Fox ◽

V Brown-Driver ◽

M J Martin ◽

R F Azad

Keyword(s):

Gene Expression ◽

Cell Culture ◽

Antiviral Activity ◽

Protein Expression ◽

Human Cytomegalovirus ◽

Host Cells ◽

Early Gene ◽

Immediate Early ◽

Mrna Levels ◽

Virus Adsorption

ISIS 2922 is a phosphorothioate oligonucleotide that is complementary to human cytomegalovirus (CMV) immediate-early (IE) RNA and that exhibits potent and specific antiviral activity against CMV in cell culture assays. Specific assay systems were developed to separately characterize the antisense and nonantisense components of the antiviral activity mediated by ISIS 2922. In U373 cells transformed with cDNA encoding the CMV IE 55-kDa (IE55) protein, expression was inhibited at nanomolar concentrations comparable to effective concentrations in antiviral assays. The specificity of inhibition was demonstrated by using control oligonucleotides incorporating progressive base changes to destabilize oligonucleotide-RNA base pairing and by showing a lack of inhibition of the CMV IE72 product expressed from the same promoter. Inhibition of IE55 protein expression correlated with a reduction in mRNA levels consistent with an RNase H-mediated termination event. Studies with virus-infected cells demonstrated that antisense and nonantisense mechanisms contribute to the antiviral activity of ISIS 2922. Base complementarity to target RNA was important for optimal activity in antiviral assays, but base changes affecting parameters other than hybridization affinity also influenced antiviral activity. Sequence-independent inhibition of virus adsorption to host cells by phosphorothioate oligonucleotides was also observed at high concentrations. Therefore, at least three different mechanisms may contribute to the antiviral activity of ISIS 2922 in cell culture: antisense-mediated inhibition of target gene expression; nonantisense, sequence-dependent inhibition of virus replication; and sequence-independent inhibition of virus adsorption to host cells.

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Potent β-Lactam Inhibitors of Human Cytomegalovirus Protease

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029800900502 ◽

1998 ◽

Vol 9 (5) ◽

pp. 379-387 ◽

Cited By ~ 23

Author(s):

C Yoakim ◽

WW Ogilvie ◽

DR Cameron ◽

C Chabot ◽

C Grand-Maître ◽

...

Keyword(s):

Cell Culture ◽

Antiviral Activity ◽

Human Cytomegalovirus ◽

Inhibitory Activity ◽

Enzymatic Assay ◽

Side Chain ◽

Plaque Reduction Assay ◽

Reduction Assay ◽

Culture Activity

A series of novel monobactam inhibitors of human cytomegalovirus (HCMV) protease has been described that possess a heterocyclic thiomethyl side chain at C-4. Changes to the heterocycle did not significantly change the inhibitory activity of these compounds in an enzymatic assay, although improvements in solubility and cell culture activity were noted. A number of permutations between C-4 substitutions and N-1 derivatives led to the identification of several β-lactams with antiviral activity in a plaque reduction assay. N-methyl thiotetrazole-containing compounds were found to be the most potent inhibitors in the enzymatic assay.

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Modeling the antiviral activity of ribavirin against hepatitis C virus in cell culture

Hepatology ◽

10.1002/hep.26493 ◽

2013 ◽

Vol 58 (4) ◽

pp. 1203-1206

Author(s):

Daniel J. Felmlee ◽

Fei Xiao ◽

Thomas F. Baumert

Keyword(s):

Cell Culture ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Activity

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Potent antiviral activity of brequinar against the emerging Cantagalo virus in cell culture

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2011.07.002 ◽

2011 ◽

Vol 38 (5) ◽

pp. 435-441 ◽

Cited By ~ 6

Author(s):

Laila Castro Schnellrath ◽

Clarissa R. Damaso

Keyword(s):

Cell Culture ◽

Antiviral Activity ◽

Potent Antiviral Activity

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Activity of Penciclovir in Combination with Azido-Thymidine, Ganciclovir, Acyclovir, Foscarnet and Human Interferons against Herpes Simplex Virus Replication in Cell Culture

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029200300203 ◽

1992 ◽

Vol 3 (2) ◽

pp. 85-94 ◽

Cited By ~ 3

Author(s):

D. Sutton ◽

J. Taylor ◽

T. H. Bacon ◽

M. R. Boyd

Keyword(s):

Cell Culture ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Antiviral Activity ◽

Antiviral Agents ◽

High Concentrations ◽

Simplex Virus ◽

Hsv 1

Combinations of penciclovir (PCV) with other antiviral agents (acyclovir, ACV; ganciclovir, GCV; foscarnet, PFA; azido-thymidine, AZT) or with human interferons (HulFN-α,β,γ) were tested for inhibitory activity against herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) in cell culture. The antiviral interactions observed between combinations of PCV with ACV or GCV were purely additive. Combinations of PCV with HulFNs demonstrated highly synergistic anti-herpesvirus activity; some synergy was also detected between PCV and PFA against HSV-1. High concentrations of AZT inhibited the antiviral activity of PCV; this antagonism was competitive. In more detailed studies it was demonstrated that high concentrations of AZT also inhibited the antiviral activity of ACV, and that ACV was more sensitive to this antagonism than PCV. It was concluded that the antagonism was unlikely to have clinical significance.

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Effect of Oral Administration of Emtricitabine on Woodchuck Hepatitis Virus Replication in Chronically Infected Woodchucks

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.6.1757-1760.2000 ◽

2000 ◽

Vol 44 (6) ◽

pp. 1757-1760 ◽

Cited By ~ 42

Author(s):

Brent E. Korba ◽

R. F. Schinazi ◽

Paul Cote ◽

Bud C. Tennant ◽

John L. Gerin

Keyword(s):

Cell Culture ◽

Antiviral Activity ◽

Oral Administration ◽

Hepatitis Virus ◽

Controlled Study ◽

Woodchuck Hepatitis Virus ◽

Dependent Manner ◽

Effective Inhibitor ◽

B Virus ◽

Dose Dependent

ABSTRACT Emtricitabine [(−)FTC] [(−)-β-2′,3′-dideoxy-5-fluoro-3′-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (−)FTC against WHV replication in chronically infected woodchucks, an established and predictive model for antiviral therapy against HBV, was examined in a placebo-controlled study. (−)FTC significantly reduced viremia and intrahepatic WHV replication in a dose-dependent manner that was comparable to the antiviral activity of lamivudine observed in previous studies conducted by our laboratories. No effect on the levels of hepatic WHV RNA or the levels of woodchuck hepatitis surface antigen or anti-woodchuck hepatitis surface and core antibodies in the serum of the treated animals was observed. No evidence of drug-related toxicity was observed in any of the animals treated.

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