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Viruses ; 13(11)2021 11 04.
Article in English | MEDLINE | ID: covidwho-1538544


Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease, which still causes large economic losses for the swine industry. Therefore, it is urgent to find a new strategy to prevent and control PRV infection. Previous studies have proven that guanine (G)-rich DNA or RNA sequences in some other viruses' genomes have the potential to form G-quadruplex (G4), which serve as promising antivirus targets. In this study, we identified two novel G4-forming sequences, OriL-A and OriL-S, which are located at the upstream origin of replication (OriL) in the PRV genome and conserved across 32 PRV strains. Circular dichroism (CD) spectroscopy and a gel electrophoresis assay showed that the two G-rich sequences can fold into parallel G4 structures in vitro. Moreover, fluorescence resonance energy transfer (FRET) melting and a Taq polymerase stop assay indicated that the G4 ligand PhenDC3 has the capacity to bind and stabilize the G4. Notably, the treatment of PRV-infected cells with G4-stabilizer PhenDC3 significantly inhibited PRV DNA replication in host cells but did not affect PRV's attachment and entry. These results not only expand our knowledge about the G4 characteristics in the PRV genome but also suggest that G4 may serve as an innovative therapeutic target against PRV.

Antiviral Agents/pharmacology , G-Quadruplexes , Herpesvirus 1, Suid/genetics , Replication Origin/genetics , Animals , Antiviral Agents/chemistry , Cell Line , DNA Replication/drug effects , DNA, Viral/biosynthesis , DNA, Viral/chemistry , DNA, Viral/drug effects , Fused-Ring Compounds/chemistry , Fused-Ring Compounds/pharmacology , G-Quadruplexes/drug effects , Genome, Viral/drug effects , Genome, Viral/genetics , Herpesvirus 1, Suid/drug effects , Herpesvirus 1, Suid/physiology , Replication Origin/drug effects , Swine , Virus Replication/drug effects
Biosci Biotechnol Biochem ; 85(5): 1170-1174, 2021 Apr 24.
Article in English | MEDLINE | ID: covidwho-1010330


Interleukin-6 (IL-6) binds to the IL-6 receptor (IL-6R) subunit, related to autoimmune diseases and cytokine storm in COVID-19. In this study, we performed systematic evolution of ligands by exponential enrichment and identified a novel RNA aptamer. This RNA aptamer not only bound to IL-6R with a dissociation constant of 200 n m, but also inhibited the interaction of IL-6R with IL-6.

Aptamers, Nucleotide/therapeutic use , Cytokine Release Syndrome/drug therapy , Interleukin-6/antagonists & inhibitors , Receptors, Interleukin-6/antagonists & inhibitors , Aptamers, Nucleotide/chemistry , Base Sequence , COVID-19/complications , Cytokine Release Syndrome/etiology , DNA, Viral/drug effects , Humans , Interleukin-6/metabolism , Receptors, Interleukin-6/metabolism , SELEX Aptamer Technique
Infect Control Hosp Epidemiol ; 42(3): 253-260, 2021 03.
Article in English | MEDLINE | ID: covidwho-1009986


BACKGROUND: Personal protective equipment (PPE) is a critical need during the coronavirus disease 2019 (COVID-19) pandemic. Alternative sources of surgical masks, including 3-dimensionally (3D) printed approaches that may be reused, are urgently needed to prevent PPE shortages. Few data exist identifying decontamination strategies to inactivate viral pathogens and retain 3D-printing material integrity. OBJECTIVE: To test viral disinfection methods on 3D-printing materials. METHODS: The viricidal activity of common disinfectants (10% bleach, quaternary ammonium sanitizer, 3% hydrogen peroxide, or 70% isopropanol and exposure to heat (50°C, and 70°C) were tested on four 3D-printed materials used in the healthcare setting, including a surgical mask design developed by the Veterans' Health Administration. Inactivation was assessed for several clinically relevant RNA and DNA pathogenic viruses, including severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and human immunodeficiency virus 1 (HIV-1). RESULTS: SARS-CoV-2 and all viruses tested were completely inactivated by a single application of bleach, ammonium quaternary compounds, or hydrogen peroxide. Similarly, exposure to dry heat (70°C) for 30 minutes completely inactivated all viruses tested. In contrast, 70% isopropanol reduced viral titers significantly less well following a single application. Inactivation did not interfere with material integrity of the 3D-printed materials. CONCLUSIONS: Several standard decontamination approaches effectively disinfected 3D-printed materials. These approaches were effective in the inactivation SARS-CoV-2, its surrogates, and other clinically relevant viral pathogens. The decontamination of 3D-printed surgical mask materials may be useful during crisis situations in which surgical mask supplies are limited.

COVID-19/prevention & control , Disinfectants/pharmacology , Disinfection/methods , Masks , SARS-CoV-2/drug effects , Virus Inactivation , 2-Propanol , DNA, Viral/drug effects , Decontamination/methods , HIV-1/drug effects , Healthy Volunteers , Hot Temperature , Humans , Hydrogen Peroxide , Personal Protective Equipment , Printing, Three-Dimensional , RNA, Viral/drug effects , Virus Diseases/prevention & control