Selection of an Antiviral RNA Aptamer Against Hemagglutinin of the Subtype H5 Avian Influenza Virus

Park, Sun Young; Kim, Se‐Ho; Yoon, Hana; Kim, Kyung-Bo; Kalme, Sheetal; Oh, Sangtaek; Song, Chang Seon; Kim, Dong-Eun

doi:10.1089/nat.2011.0321

Cited by 49 publications

(39 citation statements)

References 27 publications

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“…Interestingly, Sc5-c3 interaction with HPV-16 VLPs appears more stable than the described HPV-33 interaction with the cell surface (K d = 100 pM) which is mainly governed by electrostatic interactions and probably conserved for high-risk HPVs [14,41]. This provides an insight to the potential Sc5-c3 applications as a competitor to block HPV infection, as previously shown for aptamers against human influenza virus [42,43], hepatitis C virus [44], and cytomegalovirus [36] infections.…”

Section: Discussionsupporting

confidence: 52%

Characterization of an RNA Aptamer Against HPV-16 L1 Virus-Like Particles

Leija-Montoya¹,

Benítez‐Hess²,

Toscano-Garibay

et al. 2014

Nucleic Acid Therapeutics

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The human papillomavirus (HPV) capsid is mainly composed of the L1 protein that can self-assemble into virus-like particles (VLPs) that are structurally and immunologically similar to the infectious virions. We report here the characterization of RNA aptamers that recognize baculovirus-produced HPV-16 L1 VLPs. Interaction and slot-blot binding assays showed that all isolated aptamers efficiently bound HPV-16 VLPs, although the Sc5-c3 aptamer showed the highest specificity and affinity (K d = 0.05 pM). Sc5-c3 secondary structure consisted of a hairpin with a symmetric bubble and an unstructured 3¢end. Biochemical and genetic analyses showed that the Sc5-c3 main loop is directly involved on VLPs binding. In particular, binding specificity appeared mediated by five non-consecutive nucleotide positions. Experiments using bacterial-produced HPV-16 L1 resulted in low Sc5-c3 binding, suggesting that recognition of HPV-16 L1 VLPs relies on quaternary structure features not present in bacteria-produced L1 protein. Sc5-c3 produced specific and stable binding to HPV-16 L1 VLPs even in biofluid protein mixes and thus it may provide a potential diagnostic tool for active HPV infection.

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Section: Discussionsupporting

confidence: 52%

Characterization of an RNA Aptamer Against HPV-16 L1 Virus-Like Particles

Leija-Montoya¹,

Benítez‐Hess²,

Toscano-Garibay

et al. 2014

Nucleic Acid Therapeutics

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“…Such aptamers could be applied for both the diagnostic and the therapy of the viral infection. To create potential antiviral drugs, DNA aptamers against the globular H9 HA domain (subtype H9N2) (Choi et al, 2011) and DNA and RNA aptamers against the receptor binding region HA1 of HA (subtype Н5N1) (Cheng et al, 2008; Kwon et al, 2014; Park et al, 2011) were selected. All these aptamers possessed antiviral properties and significantly inhibited the viral infection in cell cultures.…”

Section: Antiviral Aptamersmentioning

confidence: 99%

Aptamers against pathogenic microorganisms

Davydova

Vorobjeva

Pyshnyi

et al. 2015

Critical Reviews in Microbiology

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An important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. One of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. Such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. The present review summarizes various modern SELEX techniques used in this field, and of several currently identified aptamers against viral particles and unicellular organisms, and their applications. The prospects of applying nucleic acid aptamers for the development of novel detection systems and antibacterial and antiviral drugs are discussed.

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“…Unlike ssDNA aptamers, RNA based aptamers that were developed against hemagglutinin showed specificity and selectivity to particular influenza strains [44], [45]; thus the general anti-influenza activity described in this paper may be specific to DNA-based aptamers.…”

Section: Discussionmentioning

confidence: 96%

Designing Anti-Influenza Aptamers: Novel Quantitative Structure Activity Relationship Approach Gives Insights into Aptamer – Virus Interaction

Musafia¹,

Oren-Banaroya²,

Noiman³

2014

PLoS ONE

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This study describes the development of aptamers as a therapy against influenza virus infection. Aptamers are oligonucleotides (like ssDNA or RNA) that are capable of binding to a variety of molecular targets with high affinity and specificity. We have studied the ssDNA aptamer BV02, which was designed to inhibit influenza infection by targeting the hemagglutinin viral protein, a protein that facilitates the first stage of the virus’ infection. While testing other aptamers and during lead optimization, we realized that the dominant characteristics that determine the aptamer’s binding to the influenza virus may not necessarily be sequence-specific, as with other known aptamers, but rather depend on general 2D structural motifs. We adopted QSAR (quantitative structure activity relationship) tool and developed computational algorithm that correlate six calculated structural and physicochemical properties to the aptamers’ binding affinity to the virus. The QSAR study provided us with a predictive tool of the binding potential of an aptamer to the influenza virus. The correlation between the calculated and actual binding was R2 = 0.702 for the training set, and R2 = 0.66 for the independent test set. Moreover, in the test set the model’s sensitivity was 89%, and the specificity was 87%, in selecting aptamers with enhanced viral binding. The most important properties that positively correlated with the aptamer’s binding were the aptamer length, 2D-loops and repeating sequences of C nucleotides. Based on the structure-activity study, we have managed to produce aptamers having viral affinity that was more than 20 times higher than that of the original BV02 aptamer. Further testing of influenza infection in cell culture and animal models yielded aptamers with 10 to 15 times greater anti-viral activity than the BV02 aptamer. Our insights concerning the mechanism of action and the structural and physicochemical properties that govern the interaction with the influenza virus are discussed.

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Selection of an Antiviral RNA Aptamer Against Hemagglutinin of the Subtype H5 Avian Influenza Virus

Cited by 49 publications

References 27 publications

Characterization of an RNA Aptamer Against HPV-16 L1 Virus-Like Particles

Characterization of an RNA Aptamer Against HPV-16 L1 Virus-Like Particles

Aptamers against pathogenic microorganisms

Designing Anti-Influenza Aptamers: Novel Quantitative Structure Activity Relationship Approach Gives Insights into Aptamer – Virus Interaction

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