Absence Of Antiviral Activity Research Articles

Development and Characterization of an In Silico Database of In Vitro Tested Antiviral Compounds

Antivirals are substances that inhibit viral infection or virus replication, acting as drugs to treat viral diseases. However, due the diversity of pathogens, it is important to seek new antivirals. Among the options, repositioning already approved drugs is a cheaper and faster strategy when compared to classical research and development methods. Since there is a lack of compiled and standardized data on these drugs, this work aims to build a database of in vitro antiviral tests. Thus, the compounds and their information were obtained through publications of in vitro methods for testing antiviral drugs, we created six databases covering SMILES, MOL, SDF 2D, MOL2, PDB and PDBQT extensions, classified by the presence and/or absence of antiviral activity. Each file contains its IUPAC name and structural data in up to three dimensions.

The Antiviral Activity of the Cellular Glycoprotein LGALS3BP/90K Is Species Specific.

ABSTRACTCellular antiviral proteins interfere with distinct steps of replication cycles of viruses. The galectin 3 binding protein (LGALS3BP, also known as 90K) was previously shown to lower the infectivity of nascent human immunodeficiency virus type 1 (HIV-1) virions when expressed in virus-producing cells. This antiviral effect was accompanied by impaired gp160Env processing and reduced viral incorporation of mature Env glycoproteins. Here, we examined the ability of 90K orthologs from primate species to reduce the particle infectivity of distinct lentiviruses. We show that 90K's ability to diminish the infectivity of lentiviral particles is conserved within primate species, with the notable exception of 90K from rhesus macaque. Comparison of active and inactive 90K orthologs and variants uncovered the fact that inhibition of processing of the HIV-1 Env precursor and reduction of cell surface expression of HIV-1 Env gp120 are required, but not sufficient, for 90K-mediated antiviral activity. Rather, 90K-mediated reduction of virion-associated gp120 coincided with antiviral activity, suggesting that 90K impairs the incorporation of HIV-1 Env into budding virions. We show that a single “humanizing” amino acid exchange in the BTB (broad-complex, tramtrack, and bric-à-brac)/POZ (poxvirus and zinc finger) domain is sufficient to fully rescue the antiviral activity of a shortened version of rhesus macaque 90K, but not that of the full-length protein. Comparison of the X-ray structures of the BTB/POZ domains of 90K from rhesus macaques and humans point toward a slightly larger hydrophobic patch at the surface of the rhesus macaque BTB domain that may modulate a direct interaction with either a second 90K domain or a different protein.IMPORTANCE The cellular 90K protein has been shown to diminish the infectivity of nascent HIV-1 particles. When produced in 90K-expressing cells, particles bear smaller amounts of the HIV-1 Env glycoprotein, which is essential for attaching to and entering new target cells in the subsequent infection round. However, whether the antiviral function of 90K is conserved across primates is unknown. Here, we found that 90K orthologs from most primate species, but, surprisingly, not from rhesus macaques, inhibit HIV-1. The introduction of a single amino acid exchange into a short version of the rhesus macaque 90K protein, consisting of the two intermediate domains of 90K, resulted in full restoration of antiviral activity. Structural elucidation of the respective domain suggests that the absence of antiviral activity in the rhesus macaque factor may be linked to a subtle change in protein-protein interaction.

Derivation ofHerpesvirus saimiri-Transformed CD8+T Cell Lines with Noncytotoxic Anti-HIV Activity

Herpesvirus saimiri(HVS), strain 488-77, was used to derive continuously growing transformed human CD8+T cell lines that can suppress HIV replication in CD4+cells via the production of an antiviral factor(s). Transformed CD8+cell lines were obtained by HVS infection of peripheral blood mononuclear cells or purified CD8+T cells from HIV-infected or uninfected individuals. Suppression of primary or laboratory isolates of HIV was mediated by factor permeation of a transwell membrane or by cell-free culture supernatants. Suppressing and nonsuppressing cell lines were IL-2-dependent for good growth and showed a similar activated cell surface phenotype. The cell lines produced varying amounts of the cytokines IL-8, IL-10, TNF-α, TNF-β, RANTES, MIP-1α, and MIP-1β, but not IFN-α. No correlation was observed between the level of any of these cytokines and the presence or absence of antiviral activity in cell line culture supernatants. These cell lines have become an important resource for studying antiviral factors produced by CD8+T cells from HIV-infected individuals.

Effects of levamisole, an immunomodulator, upon murine encephalomyocarditis virus myocarditis.

To test the therapeutic efficacy of levamisole, 5-week-old DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units of encephalo-myocarditis virus. Levamisole (2.5 mg/kg/per day) was administered intraperitoneally daily, starting simultaneously with the virus inoculation, in experiment I for 14 days, and daily on days 14 to 28 in experiment II in mice that survived to 14 days after virus inoculation. In experiment I, survival was higher, the severity of myocarditis was less, and myocardial virus titers were lower in treated than in untreated animals. In experiment II, levamisole was not effective. No significant changes in serum neutralizing antibody titers occurred in either experiment. Furthermore, levamisole prevented associated lymphoid organ atrophy induced by the virus infection. An additional in vitro study revealed the absence of anti-viral activity of the drug. Thus, levamisole may have favorable effects upon encephalomyocarditis virus myocarditis by preventing the virus-induced lymphoid organ atrophy and reducing myocardial virus replication in the acute stage.

Thyroid hormone potentiates the antiviral action of interferon-gamma in cultured human cells.

Human interferon-gamma (hIFN gamma) exhibits a number of biological effects, including antiviral activity in homologous cells. The antiviral activity of recombinant (r) hIFN gamma, estimated by inhibition of vesicular stomatitis virus yield, was potentiated up to 120-fold in human fibroblast (BG-9) cells exposed to free L-T4 (0.5 x 10(-10) mol/L). Thyroid hormone alone did not induce the antiviral state in BG-9 cells. L-T3 also potentiated the antiviral action of rhIFN gamma, but D-T4 and D-T3 were ineffective. The antiviral effect of hIFN alpha in BG-9 cells was not influenced by thyroid hormone. Exposure of rhIFN gamma-treated BG-9 cells to L-T4 for only 3 h was sufficient to potentiate hIFN gamma-mediated antiviral activity. Similar potentiation by L-T4 of the antiviral effect of rhIFN gamma in HeLa cell cultures was also observed. Although the mechanism of potentiation of rhIFN gamma action by thyroid hormone is incompletely understood, the absence of antiviral activity of thyroid hormone alone indicates that the iodothyronine effect does not depend upon hormonal action on genes able to be stimulated by IFN gamma.

Physiological hyporesponsiveness to influenza virus is induced by dsRNA and associated with absence of antiviral activity: [formula omitted] Univ. Tennessee, Memphis, TN 38163

Physiological hyporesponsiveness to influenza virus is induced by dsRNA and associated with absence of antiviral activity: [formula omitted] Univ. Tennessee, Memphis, TN 38163

Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2)

Recombinant B cell stimulatory factor 2 (rBSF-2) did not display any detectable level of antiviral activity when using human diploid fibroblasts, DIP-2, FS-4, FS-7, amnion-derived WISH and FL cells with vesicular stomatitis virus (VSV) and Sindbis virus as challenging agents (< 2.5 × 10 2 IU/mg). Furthermore anti-IFN-β could not neutralize the immunoglobulin-inducing activity of BSF-2. Moreover anti-BSF-2 could not neutralize the antiviral activity of IFN-β. The data indicate that BSF-2 is functionally and immunologically not related to IFNs.