Antiviral Activity of Binase against the Pandemic Influenza A (H1N1) Virus

Abstract

The lack of effective antiviral drugs restricts the control of the dangerous RNA-containing influenza A (H1N1) virus. Extracellular ribonuclease of Bacilli (binase) was shown to manifest antiviral activity during single- and multi-cycle viral replication in the range of concentrations non-toxic to epithelial cells and 0.01-0.1 multiplicity of infection. During antiviral treatment for 15-30 min, the concentration of 1 μg/ml binase reduced the amount of focus-forming units of viruses by a factor of 3-10 and suppressed the virus-induced cytopathic effect in A549 human lung cells. The possible mechanisms of interaction between the virus and enzyme are discussed. Positive charges in both binase and viral hemagglutinin cause electrostatic interaction with negatively charged sialic acid on the host cell’s surface followed by its penetration into the cell. Capsid elimination and release of viral RNA from endosome to the cytoplasm allows catalytic RNA cleavage by internalized binase. The data obtained confirm that binase is an effective antiviral agent against the pandemic influenza A (H1N1) virus. Certain progress in this field is associated with clarifying the detailed mechanism underlying the antiviral action of binase and development of the most effective way for its practical use.

A Novel Antiviral Strategy against MERS-CoV and HCoV-229E Using Binase to Target Viral Genome Replication

“…Previously, it was shown that at a concentration of 490 μg/ml, Binase is non-toxic towards human A549 cells [3]. Here, we show that Binase did not exert a cytotoxic effect towards Huh7 at 33°C (Fig.…”

“…Binase is able to enter into the eukaryotic cell cytoplasm and nucleus in 1 and 3 hours after its addition to cell culture media, respectively, and no intracellular Binase degradation by protease was detected during 48 h [2]. Media concentrations of Binase below 300 μg/ml are non-toxic for a variety of tested cell lines [2,3]. The enzyme lacks superantigen properties to induce the polyclonal T-cell immune response [4].…”

“…Antiviral activity of Binase was demonstrated in animal models against negative-stranded RNA viruses, such as rabies virus and influenza A and B viruses [5][6][7]. Previously, we have reported antiviral properties of Binase against pandemic influenza A (H1N1) virus in human cell culture [3,7]. Also, antiviral action of Binase against the positive stranded foot-and-mouth-disease virus (FMDV) has been reported.…”

The Role of Metals in the Reaction Catalyzed by Metal-Ion-Independent Bacillary RNase

“…Binase is a promising therapeutic agent with anticancer [32–36] and antivirus effects [37, 38]. Secretion of RNase by bacilli in the intestinal flora is a natural defense mechanism that counters oncogenesis and viral infections.…”

Preparations of Bacillus pumilus secreted RNase: One enzyme or two?

“…The cytotoxic effects of such microbial RNases as binase, secreted RNase of Bacillus pumilus (previously B. intermedius [1]), bar nase of B. amyloliquefaciens [2], RNase of Streptomy ces aureofaciens CCM 3239 [3], and α sarcin, a ribot oxin from fungi of the genus Aspergillus [4], against cancer cells make microbial RNases promising antitu mor agents [5][6][7][8][9]. Binase was recently shown to exhibit an antiviral effect [10], as well as to possess mutagenic [11,12] and antimutagenic properties [13]. Production of a homogenous, highly purified protein is a prerequisite for development of binase based preparations.…”