High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

Abstract

Summary Background: The development of new antiviral drugs based on nucleic acids is under scrutiny. An important problem in this aspect is to find the most vulnerable conservative regions in the viral genome as targets for the action of these agents. Another challenge is the development of an efficient system for their delivery into cells. To solve this problem, we proposed a TiO2·PL–DNA nanocomposite consisting of titanium dioxide nanoparticles and polylysine (PL)-containing oligonucleotides. Results: The TiO2·PL–DNA nanocomposites bearing the DNA fragments targeted to different conservative regions of (−)RNA and (+)RNA of segment 5 of influenza A virus (IAV) were studied for their antiviral activity in MDCK cells infected with the H1N1, H5N1, and H3N2 virus subtypes. Within the negative strand of each of the studied strains, the efficiency of DNA fragments increased in the direction of its 3’-end. Thus, the DNA fragment aimed at the 3’-noncoding region of (−)RNA was the most efficient and inhibited the reproduction of different IAV subtypes by 3–4 orders of magnitude. Although to a lesser extent, the DNA fragments targeted at the AUG region of (+)RNA and the corresponding region of (−)RNA were also active. For all studied viral subtypes, the nanocomposites bearing the DNA fragments targeted to (−)RNA appeared to be more efficient than those containing fragments aimed at the corresponding (+)RNA regions. Conclusion: The proposed TiO2·PL–DNA nanocomposites can be successfully used for highly efficient and site-specific inhibition of influenza A virus of different subtypes. Some patterns of localization of the most vulnerable regions in IAV segment 5 for the action of DNA-based drugs were found. The (−)RNA strand of IAV segment 5 appeared to be more sensitive as compared to (+)RNA.

Nanoparticles as Potential Antivirals in Agriculture

“…In the case of metal oxide nanoparticles, Levina et al [55] reported that TiO 2 •polylysine (PL)-DNA nanocomposites could be successfully used for the highly efficient and site-specific inhibition of influenza A viruses of different subtypes. Cui et al [56] reported the inactivation of H9N2 avian influenza virus in cells exposed to an anatase nano-TiO 2 solution under UV irradiation at 365 nm.…”

Non-agglomerated silicon–organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties

“…The antiviral activity of the Si–NH 2 ·ODN(4) nanocomplex was not inferior to that of the TiO 2 ·PL–ODN nanocomplexes reported in our previous papers [20–22]. The high inhibition efficiency of the virus reproduction with the use of the Si–NH 2 ·ODN nanocomplex is provided by the fact that the nanocomplex delivers ODN into the cytoplasm of the cell, and ODN can penetrate into the cell nuclei (Fig.…”

“…The antiviral activity experiments were performed analogously as described in [22]. The influenza A virus (IAV) strains and MDCK cells were prepared as in [22].…”

“…The influenza A virus (IAV) strains and MDCK cells were prepared as in [22]. The cells at ≈80% confluence were initially infected with A/chicken/Kurgan/05/2005 virus (H5N1), which was added in each well in RPMI-1640 medium (100 μL) containing trypsin (2 μg/mL) at a MOI of 0.1.…”

Nano-based approach to combat emerging viral (NIPAH virus) infection

“…134 This strategy could be effectively evaluated in vitro in case of NiV inhibition. Likewise modulation of viral transcription using MWCTs-ribavirin by Zhu et al, 135 targeted binding on conservative regions on viral genome using TiO 2 NPs and polylysine (PL)containing oligonucleotides nanocomposite by Levina et al 136 and silencing viral replication with the help of solid lipid NPs by Torrecilla et al 137 etc. all point in the same direction (Tables 1, 2, and 3).…”