scholarly journals Nucleic Acid-Based Treatments Against COVID-19: Potential Efficacy of Aptamers and siRNAs

2021 ◽  
Vol 12 ◽  
Author(s):  
Javad Khanali ◽  
Mohammadreza Azangou-Khyavy ◽  
Yasaman Asaadi ◽  
Monire Jamalkhah ◽  
Jafar Kiani
Keyword(s):  
Life Cycle ◽  
Nucleic Acid ◽  
Antiviral Therapy ◽  
Targeted Delivery ◽  
Viral Infections ◽  
Viral Life Cycle ◽  
Viral Loads ◽  
Subgenomic Rnas ◽  
Potential Efficacy ◽  
Delivery Approach

Despite significant efforts, there are currently no approved treatments for COVID-19. However, biotechnological approaches appear to be promising in the treatment of the disease. Accordingly, nucleic acid-based treatments including aptamers and siRNAs are candidates that might be effective in COVID-19 treatment. Aptamers can hamper entry and replication stages of the SARS-CoV-2 infection, while siRNAs can cleave the viral genomic and subgenomic RNAs to inhibit the viral life cycle and reduce viral loads. As a conjugated molecule, aptamer–siRNA chimeras have proven to be dual-functioning antiviral therapy, acting both as virus-neutralizing and replication-interfering agents as well as being a siRNA targeted delivery approach. Previous successful applications of these compounds against various stages of the pathogenesis of diseases and viral infections, besides their advantages over other alternatives, might provide sufficient rationale for the application of these nucleic acid-based drugs against the SARS-CoV-2. However, none of them are devoid of limitations. Here, the literature was reviewed to assess the plausibility of using aptamers, siRNAs, and aptamer–siRNA chimeras against the SARS-CoV-2 based on their previously established effectiveness, and discussing challenges lie in applying these molecules.

scholarly journals Viral Ubiquitin and Ubiquitin-Like Deconjugases—Swiss Army Knives for Infection

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1137
Author(s):  
Maria Grazia Masucci
Keyword(s):  
Life Cycle ◽  
Posttranslational Modifications ◽  
Viral Infections ◽  
Functional Characterization ◽  
Viral Life Cycle ◽  
Cellular Proteins ◽  
Antiviral Defense ◽  
Cellular Processes ◽  
Growing Body

Posttranslational modifications of cellular proteins by covalent conjugation of ubiquitin and ubiquitin-like polypeptides regulate numerous cellular processes that are captured by viruses to promote infection, replication, and spreading. The importance of these protein modifications for the viral life cycle is underscored by the discovery that many viruses encode deconjugases that reverse their functions. The structural and functional characterization of these viral enzymes and the identification of their viral and cellular substrates is providing valuable insights into the biology of viral infections and the host’s antiviral defense. Given the growing body of evidence demonstrating their key contribution to pathogenesis, the viral deconjugases are now recognized as attractive targets for the design of novel antiviral therapeutics.

scholarly journals When MARCH family proteins meet viral infections

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chunfu Zheng ◽  
Yan-Dong Tang
Keyword(s):  
Life Cycle ◽  
Viral Infection ◽  
Viral Infections ◽  
Ring Finger ◽  
Ubiquitin Ligases ◽  
Viral Life Cycle ◽  
Ring Finger Domain ◽  
E3 Ligases

AbstractMembrane-associated RING-CH (MARCH) ubiquitin ligases belong to a RING finger domain E3 ligases family. Recent studies have demonstrated that MARCH proteins play critical roles during various viral infections. MARCH proteins can directly antagonize different steps of the viral life cycle and promote individual viral infection. This mini-review will focus on the latest advances of MARCH family proteins' emerging roles during viral infections.

scholarly journals Ceramide and Related Molecules in Viral Infections

2021 ◽  
Vol 22 (11) ◽  
pp. 5676
Author(s):  
Nadine Beckmann ◽  
Katrin Anne Becker
Keyword(s):  
Life Cycle ◽  
Viral Entry ◽  
Immune Modulation ◽  
Viral Infections ◽  
Therapeutic Benefit ◽  
Viral Life Cycle ◽  
Endosomal Escape ◽  
Sphingolipid Metabolism ◽  
Cell Surface Expression ◽  
Membrane Microdomains

Ceramide is a lipid messenger at the heart of sphingolipid metabolism. In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains. Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression. Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking. Ceramide can be key for the formation of viral replication sites. Sphingomyelinases often mediate the release of new virions from infected cells. Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion. Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections. This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle. We will also discuss how novel strategies could exploit these for therapeutic benefit.

scholarly journals Significant Differences in RNA Structure Destabilization by HIV-1 Gag∆p6 and NCp7 Proteins

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 484 ◽  
Author(s):  
Micah J. McCauley ◽  
Ioulia Rouzina ◽  
Jasmine Li ◽  
Megan E. Núñez ◽  
Mark C. Williams
Keyword(s):  
Life Cycle ◽  
Nucleic Acid ◽  
Optical Tweezers ◽  
Reverse Transcription ◽  
Rna Binding ◽  
Specific Antigen ◽  
Viral Life Cycle ◽  
Tar Rna ◽  
Rna Hairpin ◽  
Hiv 1

Retroviral nucleocapsid (NC) proteins are nucleic acid chaperones that play distinct roles in the viral life cycle. During reverse transcription, HIV-1 NC facilitates the rearrangement of nucleic acid secondary structures, allowing the transactivation response (TAR) RNA hairpin to be transiently destabilized and annealed to a complementary RNA hairpin. In contrast, during viral assembly, NC, as a domain of the group-specific antigen (Gag) polyprotein, binds the genomic RNA and facilitates packaging into new virions. It is not clear how the same protein, alone or as part of Gag, performs such different RNA binding functions in the viral life cycle. By combining single-molecule optical tweezers measurements with a quantitative mfold-based model, we characterize the equilibrium stability and unfolding barrier for TAR RNA. Comparing measured results with a model of discrete protein binding allows us to localize affected binding sites, in addition to quantifying hairpin stability. We find that, while both NCp7 and Gag∆p6 destabilize the TAR hairpin, Gag∆p6 binding is localized to two sites in the stem, while NCp7 targets sites near the top loop. Unlike Gag∆p6, NCp7 destabilizes this loop, shifting the location of the reaction barrier toward the folded state and increasing the natural rate of hairpin opening by ~104. Thus, our results explain why Gag cleavage and NC release is an essential prerequisite for reverse transcription within the virion.

scholarly journals Broad Anti-Viral Capacities of Lian-Hua-Qing-Wen Capsule and Jin-Hua-Qing-Gan Granule and Rational use Against COVID-19 Based on Literature Mining

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingfei Shi ◽  
Bo Peng ◽  
An Li ◽  
Ziyun Li ◽  
Ping Song ◽  
...  
Keyword(s):  
Life Cycle ◽  
Viral Infections ◽  
Combined Treatment ◽  
Modern Medicine ◽  
Vital Role ◽  
Clinical Applications ◽  
Viral Life Cycle ◽  
Literature Mining ◽  
Immune Functions ◽  
Novel Coronavirus

The novel coronavirus disease 2019 (COVID-19) has become a matter of international concern as the disease is spreading exponentially. Statistics showed that infected patients in China who received combined treatment of Traditional Chinese Medicine and modern medicine exhibited lower fatality rate and relatively better clinical outcomes. Both Lian-Hua-Qing-Wen Capsule (LHQWC) and Jin-Hua-Qing-Gan Granule (JHQGG) have been recommended by China Food and Drug Administration for the treatment of COVID-19 and have played a vital role in the prevention of a variety of viral infections. Here, we desired to analyze the broad-spectrum anti-viral capacities of LHQWC and JHQGG, and to compare their pharmacological functions for rational clinical applications. Based on literature mining, we found that both LHQWC and JHQGG were endowed with multiple antiviral activities by both targeting viral life cycle and regulating host immune responses and inflammation. In addition, from literature analyzed, JHQGG is more potent in modulating viral life cycle, whereas LHQWC exhibits better efficacies in regulating host anti-viral responses. When translating into clinical applications, oral administration of LHQWC could be more beneficial for patients with insufficient immune functions or for patients with alleviated symptoms after treatment with JHQGG.

The diagnosis of hepatitis C viral infection

2014 ◽  
Vol 155 (26) ◽  
pp. 1019-1023
Author(s):  
Judit Gervain
Keyword(s):  
Hepatitis C ◽  
Nucleic Acid ◽  
Viral Infection ◽  
Structural Changes ◽  
Viral Infections ◽  
Transient Elastography ◽  
Viral Nucleic Acid ◽  
Length Of Treatment ◽  
Subtype B

The successful therapy of hepatitis C viral infection requires that the illness is diagnosed before the development of structural changes of the liver. Testing is stepwise consisting of screening, diagnosis, and anti-viral therapy follow-up. For these steps there are different biochemical, serological, histological and molecular biological methods available. For screening, alanine aminotransferase and anti-HCV tests are used. The diagnosis of infection is confirmed using real-time polymerase chain reaction of the viral nucleic acid. Before initiation of the therapy liver biopsy is recommended to determine the level of structural changes in the liver. Alternatively, transient elastography or blood biomarkers may be also used for this purpose. Differential diagnosis should exclude the co-existence of other viral infections and chronic hepatitis due to other origin, with special attention to the presence of autoantibodies. The outcome of the antiviral therapy and the length of treatment are mainly determined by the viral genotype. In Hungary, most patients are infected with genotype 1, subtype b. The polymorphism type that occurs in the single nucleotide located next to the interleukin 28B region in chromosome 19 and the viral polymorphism type Q80K for infection with HCV 1a serve as predictive therapeutic markers. The follow-up of therapy is based on the quantitative determination of viral nucleic acid according to national and international protocols and should use the same method and laboratory throughout the treatment of an individual patient. Orv. Hetil., 2014, 155(26), 1019–1023.

scholarly journals Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Federica Palombarini ◽  
Silvia Masciarelli ◽  
Alessio Incocciati ◽  
Francesca Liccardo ◽  
Elisa Di Fabio ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Targeted Delivery ◽  
Myeloid Leukemia ◽  
Electrostatic Interactions ◽  
Archaeoglobus Fulgidus ◽  
Leukemia Cells ◽  
Cellular Delivery ◽  
Self Assembling ◽  
Wide Range ◽  
Hybrid Nanoparticle

Abstract Background In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. Results Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. Conclusion The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells. Graphic abstract

scholarly journals Nucleosome Positioning on Episomal Human Papillomavirus DNA in Cultured Cells

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 772
Author(s):  
Isao Murakami ◽  
Takashi Iwata ◽  
Tohru Morisada ◽  
Kyoko Tanaka ◽  
Daisuke Aoki
Keyword(s):  
Life Cycle ◽  
Cultured Cells ◽  
Basal Layer ◽  
Nucleosome Positioning ◽  
Viral Life Cycle ◽  
Human Papillomaviruses ◽  
Host Cells ◽  
Micrococcal Nuclease ◽  
Hpv Dna ◽  
Dna Replication And Repair

Several human papillomaviruses (HPV) are associated with the development of cervical carcinoma. HPV DNA synthesis is increased during the differentiation of infected host keratinocytes as they migrate from the basal layer of the epithelium to the spinous layer, but the molecular mechanism is unclear. Nucleosome positioning affects various cellular processes such as DNA replication and repair by permitting the access of transcription factors to promoters to initiate transcription. In this study, nucleosome positioning on virus chromatin was investigated in normal immortalized keratinocytes (NIKS) stably transfected with HPV16 or HPV18 genomes to determine if there is an association with the viral life cycle. Micrococcal nuclease-treated DNA analyzed by Southern blotting using probes against HPV16 and HPV18 and quantified by nucleosome scanning analysis using real-time PCR revealed mononucleosomal-sized fragments of 140–200 base pairs that varied in their location within the viral genome according to whether the cells were undergoing proliferation or differentiation. Notably, changes in the regions around nucleotide 110 in proliferating and differentiating host cells were common to HPV16 and HPV18. Our findings suggest that changes in nucleosome positions on viral DNA during host cell differentiation is an important regulatory event in the viral life cycle.

scholarly journals A Comprehensive, Flexible Collection of SARS-CoV-2 Coding Regions

2020 ◽  
Vol 10 (9) ◽  
pp. 3399-3402 ◽  
Author(s):  
Dae-Kyum Kim ◽  
Jennifer J Knapp ◽  
Da Kuang ◽  
Aditya Chawla ◽  
Patricia Cassonnet ◽  
...  
Keyword(s):  
Life Cycle ◽  
Viral Life Cycle ◽  
Coding Sequences ◽  
Coding Regions ◽  
Global Pandemic ◽  
The World ◽  
Molecular Studies ◽  
Widespread Availability ◽  
Rapid Transfer

Abstract The world is facing a global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus. Here we describe a collection of codon-optimized coding sequences for SARS-CoV-2 cloned into Gateway-compatible entry vectors, which enable rapid transfer into a variety of expression and tagging vectors. The collection is freely available. We hope that widespread availability of this SARS-CoV-2 resource will enable many subsequent molecular studies to better understand the viral life cycle and how to block it.

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