scholarly journals Identification and Structural Aspects of G-Quadruplex-Forming Sequences from the Influenza A Virus Genome

2021 ◽  
Vol 22 (11) ◽  
pp. 6031
Author(s):  
Maria Tomaszewska ◽  
Marta Szabat ◽  
Karolina Zielińska ◽  
Ryszard Kierzek
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Virus Genome ◽  
High Variability ◽  
Research Subject ◽  
Important Research ◽  
G Quadruplex ◽  
2009 H1n1 ◽  
Seasonal Epidemics ◽  
Structural Aspects

Influenza A virus (IAV) causes seasonal epidemics and sporadic pandemics, therefore is an important research subject for scientists around the world. Despite the high variability of its genome, the structure of viral RNA (vRNA) possesses features that remain constant between strains and are biologically important for virus replication. Therefore, conserved structural motifs of vRNA can represent a novel therapeutic target. Here, we focused on the presence of G-rich sequences within the influenza A/California/07/2009(H1N1) genome and their ability to form RNA G-quadruplex structures (G4s). We identified 12 potential quadruplex-forming sequences (PQS) and determined their conservation among the IAV strains using bioinformatics tools. Then we examined the propensity of PQS to fold into G4s by various biophysical methods. Our results revealed that six PQS oligomers could form RNA G-quadruplexes. However, three of them were confirmed to adopt G4 structures by all utilized methods. Moreover, we showed that these PQS motifs are present within segments encoding polymerase complex proteins indicating their possible role in the virus biology.

scholarly journals The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus

2021 ◽  
Vol 22 (5) ◽  
pp. 2409
Author(s):  
Anastasia A. Bizyaeva ◽  
Dmitry A. Bunin ◽  
Valeria L. Moiseenko ◽  
Alexandra S. Gambaryan ◽  
Sonja Balk ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Core Structure ◽  
Dna Aptamer ◽  
Tertiary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Flanking Sequences ◽  
Related Proteins

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

Evidence for specific packaging of the influenza A virus genome from conditionally defective virus particles lacking a polymerase gene

Vaccine ◽  
2006 ◽  
Vol 24 (44-46) ◽  
pp. 6647-6650 ◽  
Author(s):  
Emmie de Wit ◽  
Monique I.J. Spronken ◽  
Guus F. Rimmelzwaan ◽  
Albert D.M.E. Osterhaus ◽  
Ron A.M. Fouchier
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Virus Genome ◽  
Polymerase Gene ◽  
Virus Particles ◽  
Defective Virus

Cross-Protective Effect of Antisense Oligonucleotide Developed Against the Common 3′ NCR of Influenza A Virus Genome

2013 ◽  
Vol 55 (3) ◽  
pp. 203-211 ◽  
Author(s):  
Prashant Kumar ◽  
Binod Kumar ◽  
Roopali Rajput ◽  
Latika Saxena ◽  
Akhil C. Banerjea ◽  
...  
Keyword(s):  
Protective Effect ◽  
Influenza A Virus ◽  
Antisense Oligonucleotide ◽  
Influenza A ◽  
Virus Genome ◽  
The Common

scholarly journals A new common mutation in the hemagglutinin of the 2009 (H1N1) influenza A virus

PLoS Currents ◽  
2010 ◽  
Vol 2 ◽  
pp. RRN1162 ◽  
Author(s):  
Sebastian Maurer-Stroh ◽  
Raphael Tze Chuen Lee ◽  
Frank Eisenhaber ◽  
Lin Cui ◽  
Shiau Pheng Phuah ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Common Mutation ◽  
2009 H1n1

scholarly journals Codon conservation in the influenza A virus genome defines RNA packaging signals

2007 ◽  
Vol 35 (6) ◽  
pp. 1897-1907 ◽  
Author(s):  
Julia R. Gog ◽  
Emmanuel Dos Santos Afonso ◽  
Rosa M. Dalton ◽  
India Leclercq ◽  
Laurence Tiley ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Virus Genome ◽  
Rna Packaging ◽  
Packaging Signals

scholarly journals Inactivated pandemic 2009 H1N1 influenza A virus human vaccines have different efficacy after homologous challenge in the ferret model

2020 ◽  
Vol 15 (1) ◽  
pp. 142-153
Author(s):  
Beatriz Vidaña ◽  
Sharon M. Brookes ◽  
Helen E. Everett ◽  
Fanny Garcon ◽  
Alejandro Nuñez ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
2009 H1n1 ◽  
Homologous Challenge

scholarly journals A Quinolinone Compound Inhibiting the Oligomerization of Nucleoprotein of Influenza A Virus Prevents the Selection of Escape Mutants

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 337
Author(s):  
Juliann Nzembi Makau ◽  
Ken Watanabe ◽  
Hiroki Otaki ◽  
Satoshi Mizuta ◽  
Takeshi Ishikawa ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Nuclear Export ◽  
Influenza A ◽  
Drug Resistant ◽  
In Silico Screening ◽  
Antiviral Compound ◽  
Escape Mutants ◽  
2009 H1n1 ◽  
Emergence Of Resistance ◽  
Selection Of

The emergence of resistance to currently available anti-influenza drugs has heightened the need for antivirals with novel mechanisms of action. The influenza A virus (IAV) nucleoprotein (NP) is highly conserved and essential for the formation of viral ribonucleoprotein (vRNP), which serves as the template for replication and transcription. Recently, using in silico screening, we identified an antiviral compound designated NUD-1 (a 4-hydroxyquinolinone derivative) as a potential inhibitor of NP. In this study, we further analyzed the interaction between NUD-1 and NP and found that the compound interferes with the oligomerization of NP, which is required for vRNP formation, leading to the suppression of viral transcription, protein synthesis, and nuclear export of NP. We further assessed the selection of resistant variants by serially passaging a clinical isolate of the 2009 H1N1 pandemic influenza virus in the presence of NUD-1 or oseltamivir. NUD-1 did not select for resistant variants after nine passages, whereas oseltamivir selected for resistant variants after five passages. Our data demonstrate that NUD-1 interferes with the oligomerization of NP and less likely induces drug-resistant variants than oseltamivir; hence, it is a potential lead compound for the development of novel anti-influenza drugs.

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