To accelerate the Zika beat: Candidate design for RNA interference-based therapy

Giulietti, Matteo; Righetti, Alessandra; Cianfruglia, L.; Sabanovic, Berina; Armeni, Tatiana; Principato, Giovanni; Piva, Francesco

doi:10.1016/j.virusres.2018.07.010

Cited by 16 publications

(7 citation statements)

References 86 publications

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“…They reported 24 pre-miRNA hairpins, 131 siRNAs, 12 human miRNA, and 10 siRNA molecules as active therapeutic agents against SARS-CoV-2 [28]. Previous studies have examined the antiviral defense potential of several miRNAs and siRNAs against some viruses including HIV-1 [29], Influenza [30], Zika [31] and Hepatitis C (HCV) [32]. These information introduced some antiviral RNAi therapeutics that could effectively inactivate SARS-CoV-2 [6].…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of RNA interference components in COVID-19 patients

et al. 2021

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Objective Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals. Results Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of RNA interference components in COVID-19 patients

et al. 2021

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“…The current stage of anti-ZIKV drug discovery demands novel approaches to identify new inhibitors which may provide completely new class of antiviral drugs including Zika drugs. The approaches should include knowledge-based drug repurposing [143], RNA interference [144], long noncoding RNAs [145], interfering peptides [146,147], compounds targeting viral RNA [148][149][150], and computer-assisted molecular design including pharmacophore modeling [93]. Repurposing approach of old drugs allows to focus on certain types of candidates, such as kinase inhibitors and antimalarial drugs.…”

Section: Other Approachesmentioning

confidence: 99%

“…Therefore, these novel host-based targets have the potential for developing broad-spectrum antiviral drugs including anti-ZIKV drugs. In addition, bioinformatic approach generated from targets like siRNA [144] and interacting peptides [147] could be useful for ZIKV drug discovery.…”

Section: Other Approachesmentioning

confidence: 99%

Computer-Assisted and Data Driven Approaches for Surveillance, Drug Discovery, and Vaccine Design for the Zika Virus

et al. 2019

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Human life has been at the edge of catastrophe for millennia due diseases which emerge and reemerge at random. The recent outbreak of the Zika virus (ZIKV) is one such menace that shook the global public health community abruptly. Modern technologies, including computational tools as well as experimental approaches, need to be harnessed fast and effectively in a coordinated manner in order to properly address such challenges. In this paper, based on our earlier research, we have proposed a four-pronged approach to tackle the emerging pathogens like ZIKV: (a) Epidemiological modelling of spread mechanisms of ZIKV; (b) assessment of the public health risk of newly emerging strains of the pathogens by comparing them with existing strains/pathogens using fast computational sequence comparison methods; (c) implementation of vaccine design methods in order to produce a set of probable peptide vaccine candidates for quick synthesis/production and testing in the laboratory; and (d) designing of novel therapeutic molecules and their laboratory testing as well as validation of new drugs or repurposing of drugs for use against ZIKV. For each of these stages, we provide an extensive review of the technical challenges and current state-of-the-art. Further, we outline the future areas of research and discuss how they can work together to proactively combat ZIKV or future emerging pathogens.

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“…The Zika virus genetic material consists of a ~10-kb single-stranded positive-sense RNA chain containing a 5′ untranslated region (UTR) with ~100 nucleotides (nt) and a single open reading frame of ~10 kb, and ~420-nt 3′ UTR [ 5 ]. It expresses a polyprotein with 3000 amino acids separated into structural (capsid, C; precursor membrane, prM; and envelope protein, E) and nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [ 6 , 7 , 8 , 9 ] proteins. Viral replication functional complexes are formed in specific replication compartments of the endoplasmic reticulum (ER) with the participation of all seven proteins in the nonstructural group [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Quantum Biochemistry and MM-PBSA Description of the ZIKV NS2B-NS3 Protease: Insights into the Binding Interactions beyond the Catalytic Triad Pocket

Paula

Tilburg

Morais

et al. 2022

IJMS

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The Zika virus protease NS2B-NS3 has a binding site formed with the participation of a H51-D75-S135 triad presenting two forms, active and inactive. Studies suggest that the inactive conformation is a good target for the design of inhibitors. In this paper, we evaluated the co-crystallized structures of the protease with the inhibitors benzoic acid (5YOD) and benzimidazole-1-ylmethanol (5H4I). We applied a protocol consisting of two steps: first, classical molecular mechanics energy minimization followed by classical molecular dynamics were performed, obtaining stabilized molecular geometries; second, the optimized/relaxed geometries were used in quantum biochemistry and molecular mechanics/Poisson–Boltzmann surface area (MM-PBSA) calculations to estimate the ligand interactions with each amino acid residue of the binding pocket. We show that the quantum-level results identified essential residues for the stabilization of the 5YOD and 5H4I complexes after classical energy minimization, matching previously published experimental data. The same success, however, was not observed for the MM-PBSA simulations. The application of quantum biochemistry methods seems to be more promising for the design of novel inhibitors acting on NS2B-NS3.

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To accelerate the Zika beat: Candidate design for RNA interference-based therapy

Cited by 16 publications

References 86 publications

Dysregulation of RNA interference components in COVID-19 patients

Dysregulation of RNA interference components in COVID-19 patients

Computer-Assisted and Data Driven Approaches for Surveillance, Drug Discovery, and Vaccine Design for the Zika Virus

Quantum Biochemistry and MM-PBSA Description of the ZIKV NS2B-NS3 Protease: Insights into the Binding Interactions beyond the Catalytic Triad Pocket

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