scholarly journals Antiviral Activity of PD-L1 and PD-L4, Type 1 Ribosome Inactivating Proteins from Leaves of Phytolacca dioica L. in the Pathosystem Phaseolus vulgaris–Tobacco Necrosis Virus (TNV)

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 524
Author(s):  
Daniela Bulgari ◽  
Nicola Landi ◽  
Sara Ragucci ◽  
Franco Faoro ◽  
Antimo Di Maro
Keyword(s):  
Cell Death ◽  
Phaseolus Vulgaris ◽  
Antiviral Activity ◽  
Early Stage ◽  
Host Cells ◽  
Tobacco Necrosis Virus ◽  
Necrosis Virus ◽  
Ribosome Inactivating Proteins ◽  
Strong Antiviral Activity

Using the pathosystem Phaseolus vulgaris–tobacco necrosis virus (TNV), we demonstrated that PD-L1 and PD-L4, type-1 ribosome inactivating proteins (RIPs) from leaves of Phytolacca dioica L., possess a strong antiviral activity. This activity was exerted both when the RIPs and the virus were inoculated together in the same leaf and when they were inoculated or applied separately in the adaxial and abaxial leaf surfaces. This suggests that virus inhibition would mainly occur inside plant cells at the onset of infection. Histochemical studies showed that both PD-L1 and PD-L4 were not able to induce oxidative burst and cell death in treated leaves, which were instead elicited by inoculation of the virus alone. Furthermore, when RIPs and TNV were inoculated together, no sign of H2O2 deposits and cell death were detectable, indicating that the virus could have been inactivated in a very early stage of infection, before the elicitation of a hypersensitivity reaction. In conclusion, the strong antiviral activity is likely exerted inside host cells as soon the virus disassembles to start translation of the viral genome. This activity is likely directed towards both viral and ribosomal RNA, explaining the almost complete abolition of infection when virus and RIP enter together into the cells.

Injured cells required for the initiation of plant virus infections

1969 ◽  
Vol 47 (3) ◽  
pp. 499-500 ◽  
Author(s):  
W. C. Kimmins ◽  
M. D. Casselman
Keyword(s):  
Phaseolus Vulgaris ◽  
Virus Infection ◽  
Plant Virus ◽  
Tobacco Necrosis Virus ◽  
Virus Infections ◽  
Necrosis Virus

To investigate whether a plant virus infection could be initiated in uninjured cells, the trifoliate leaves of Phaseolus vulgaris var. Prince were dipped into suspensions of tobacco necrosis virus. It is concluded that infection can only be established through injured leaf cells.

scholarly journals Antiviral Activity of a Turbot (Scophthalmus maximus) NK-Lysin Peptide by Inhibition of Low-pH Virus-Induced Membrane Fusion

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 87 ◽  
Author(s):  
Alberto Falco ◽  
Regla Medina-Gali ◽  
José Poveda ◽  
Melissa Bello-Perez ◽  
Beatriz Novoa ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Scophthalmus Maximus ◽  
Low Ph ◽  
Host Cells ◽  
Viral Origin ◽  
Membrane Rupture ◽  
Viral Particles ◽  
Strong Antiviral Activity ◽  
Turbot Scophthalmus Maximus

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl71–100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl71–100 with different glycerophospholipid vesicles. At acidic pH, Nkl71–100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl71–100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl71–100 is shown as a promising broad-spectrum antiviral candidate.

scholarly journals A Polyphenol Rich Extract from Solanum melongena L. DR2 Peel Exhibits Antioxidant Properties and Anti-Herpes Simplex virus Type 1 Activity In Vitro

2018 ◽  
Author(s):  
Antonella Di Sotto ◽  
Silvia Di Giacomo ◽  
Donatella Amatore ◽  
Marcello Locatelli ◽  
Annabella Vitalone ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antioxidant Properties ◽  
Solanum Melongena ◽  
Vero Cells ◽  
Host Cells ◽  
Reducing Conditions ◽  
Simplex Virus ◽  
Hsv 1

DR2B and DR2C extracts, from peel of commercially and physiologically ripe eggplants, were studied for the antioxidative cytoprotective properties and anti-HSV-1 activity, in line with the evidence that several antioxidants can impair viral replication by maintaining reducing conditions into the host cells. The antioxidative cytoprotective effects against tBOOH-induced damage was assessed in Caco2 cells, while the antiviral activity was studied in Vero cells; phenolic and anthocyanin fingerprint was characterized by integrated phytochemical methods. Results highlighted different compositions of the extracts, with chlorogenic acid and delphinidin-3-rutinoside as the major constituents; other peculiar phytochemicals were also identified. DR2C resulted able to partly counteract the tBOOH-induced cytotoxicity, with a remarkable lowering of lactate metabolism under both normoxia and hypoxia. DR2B and DR2C reduced ROS production, possessed scavenging and chelating properties. Interestingly, DR2C increased intracellular GSH levels. Furthermore, DR2C inhibited the HSV-1 replication when added for 24 h after viral adsorption, as also confirmed by the reduction of many viral proteins expression. Since DR2C was able to reduce NOX4 expression during HSV-1 infection, its antiviral activity may be correlated to its antioxidant properties. Although further studies are needed to better characterize DR2C activity, the results suggest this extract as a promising new anti-HSV-1 agent.

Inhibition of Herpes Simplex Virus by Polyamines

2009 ◽  
Vol 20 (2) ◽  
pp. 87-98 ◽  
Author(s):  
Ira Yudovin-Farber ◽  
Irina Gurt ◽  
Ronen Hope ◽  
Abraham J Domb ◽  
Ehud Katz
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Clinical Investigation ◽  
Host Cells ◽  
Direct Exposure ◽  
Simplex Virus ◽  
Hsv 1

Background: Herpes simplex virus (HSV) establishes latent infection in humans with periodic reactivation. Acyclovir, valacyclovir and foscarnet are in medical use today against HSV type-1 (HSV-1) and type-2 (HSV-2), inhibiting the DNA synthesis of the viruses. Additional drugs that will affect the growth of these viruses by other mechanisms and also decrease the frequency of appearance of drug-resistant mutants are required. Methods: Cationic polysaccharides were synthesized by conjugation of various oligoamines to oxidized polysaccharides by reductive amination. Polycations of dextran, pullulan and arabinogalactan were grafted with oligoamines of 2–4 amino groups forming Schiff-base imine-based conjugates followed by reduction with borohydride to obtain the stable amine-based conjugate. Evaluation of toxicity to BS-C-1 cells and antiviral activity against HSV-1 and HSV-2 of the different compounds was performed in vitro by a semiquantitative assay. A quantitative study with a selected compound followed. Results: Structure–activity relationship studies showed that the nature of the grafted oligoamine of the polycation plays an essential role in the antiviral activity against HSV-1 and HSV-2. Dextran-propan-1,3-diamine (DPD) was found to be the most potent of all the compounds examined. DPD did not decrease the infectivity of HSV upon direct exposure to the virions. The growth of HSV was significantly inhibited when DPD was added to the host cells 1 h prior to infection, thus preventing the adsorption and penetration of the virus into the cells. Conclusions: Our in vitro data warrant clinical investigation. DPD could have an advantage as a topical application in combination therapy of HSV lesions.

scholarly journals Inhibition of Cyclin-Dependent Kinase 1 by Purines and Pyrrolo[2,3-d]Pyrimidines Does Not Correlate with Antiviral Activity

2002 ◽  
Vol 46 (8) ◽  
pp. 2470-2476 ◽  
Author(s):  
David L. Evers ◽  
Julie M. Breitenbach ◽  
Katherine Z. Borysko ◽  
Leroy B. Townsend ◽  
John C. Drach
Keyword(s):  
Antiviral Activity ◽  
Early Stage ◽  
Nucleoside Analogs ◽  
Cyclin B ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinases ◽  
Hcmv Replication ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT We have previously shown that a series of nonnucleoside pyrrolo[2,3-d]pyrimidines selectively inhibit the replication of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). These compounds act at the immediate-early or early stage of HCMV replication and have antiviral properties somewhat similar to those of roscovitine and olomoucine, specific inhibitors of cyclin-dependent kinases (cdks). In the present study we examine the hypothesis that pyrrolo[2,3-d]pyrimidines exert their antiviral effects by inhibition of cellular cdks. Much higher concentrations of a panel of pyrrolo[2,3-d]pyrimidine nucleoside analogs with antiviral activity were required to inhibit recombinant cdk1/cyclin B compared to the submicromolar concentrations required to inhibit HCMV and HSV-1 replication. 4,6-Diamino-5-cyano-7-(2-phenylethyl)pyrrolo[2,3-d]pyrimidine (compound 1369) was the best inhibitor of cdk1 and cyclin B, with a 50% inhibitory concentration (IC50; 14 μM) similar to that of roscovitine; it was competitive with respect to ATP (Ki = 14 μM). The potency of compound 1369 against cdk1 and cyclin B was similar to its cytotoxicity (IC50s, 32 to 100 μM) but not its antiviral efficacy (IC50s, 0.02 to 0.3 μM). Thus, our results indicated the null hypothesis. In contrast, roscovitine was only weakly active against HSV-1 (IC50, 38 μM) and HCMV (IC50, 40 μM). These values were similar to those derived by cytotoxicity and cell growth inhibition assays, thereby suggesting that roscovitine is not a selective antiviral. Therefore, we propose that inhibition of cdk1 and cyclin B is not responsible for selective antiviral activity and that pyrrolo[2,3-d]pyrimidines constitute novel pharmacophores which compete with ATP to inhibit cdk1 and cyclin B.

scholarly journals Preferential Cytolysis of Peripheral Memory CD4+ T Cells by In Vitro X4-Tropic Human Immunodeficiency Virus Type 1 Infection before the Completion of Reverse Transcription

2008 ◽  
Vol 82 (18) ◽  
pp. 9154-9163 ◽  
Author(s):  
Yan Zhou ◽  
Lin Shen ◽  
Hung-Chih Yang ◽  
Robert F. Siliciano
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Reverse Transcription ◽  
Host Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT CD4+ T-cell depletion is the hallmark of AIDS pathogenesis. Multiple mechanisms may contribute to the death of productively infected CD4+ T cells and innocent-bystander cells. In this study, we characterize a novel mechanism in which human immunodeficiency virus type 1 (HIV-1) infection preferentially depletes peripheral memory CD4+ T cells before the completion of reverse transcription. Using a recombinant HIV-1 carrying the green fluorescent protein reporter gene, we demonstrate that memory CD4+ T cells were susceptible to infection-induced cell death at a low multiplicity of infection. Infected memory CD4+ T cells underwent rapid necrotic cell death. Killing of host cells was dependent on X4 envelope-mediated viral fusion, but not on virion-associated Vpr or Nef. In contrast to peripheral resting CD4+ T cells, CD4+ T cells stimulated by mitogen or certain cytokines were resistant to HIV-1-induced early cell death. These results demonstrate that early steps in HIV-1 infection have a detrimental effect on certain subsets of CD4+ T cells. The early cell death may serve as a selective disadvantage for X4-tropic HIV-1 in acute infection but may play a role in accelerated disease progression, which is associated with the emergence of X4-tropic HIV-1 in the late stage of AIDS.

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