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Biobased Products for Viral Diseases
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Gleice Ribeiro Orasmo, Giovanna Morghanna Barbosa do Nascimento, Maria Gabrielly de Alcântara Oliveira, Jéssica Missilany da Costa
Traditional Chinese medicine has recommended the use of licorice (Glycyrrhiza glabra L.) in the treatment of infections caused by SARS-CoV-2, since the active agent, glycyrrhizin, induced effective antiviral activity against SARS coronavirus, inhibiting virus replication (Cinatl et al. 2003). More recently, a study showed that the virus ACE-2 receptor was disturbed by glycyrrhizic acid and glicasperin A, which showed high affinity for the endoribonuclease Nsp15, inhibiting virus replication. The authors concluded that glycosperin A and glycyrrhizic acid can be considered the best licorice molecules, useful against COVID-19 (Sinha et al. 2020).
Neuropathogenesis of viral infections
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Avindra Nath, Joseph R. Berger
Once a cell binds IFN-α or IFN-β, which use a common receptor, a cascade of cellular signaling occurs resulting in the transcription of several proteins that aid in conferring a hostile environment to viral infection. There are three key antiviral proteins that have been identified as a result of this transcriptional activation: 2′–5′ oligoadenylate synthetase, protein kinase PKR and Mx protein [31]. The 2′–5′ oligoadenylate synthetase polymerizes adenosine triphosphate into a series of 2′–5′ linked oligomers, which differs from normal nucleotides that are joined 3′–5′. These oligomers in turn activate RNase L, a constitutive endoribonuclease. This enzyme degrades viral RNA. Protein kinase PKR is activated by the presence of double-stranded RNA. Upon activation, PKR phosphorylates the cellular translation initiation factor eIF-2. The result of this is an inhibition of translation and protein synthesis, contributing to the inhibition of viral replication. The Mx protein is a protein that acts in the nucleus of an infected cell to confer resistance to influenza virus. The Mx protein acts in the nucleus of the cell infected with influenza and inhibits the synthesis of the influenza virus mRNA [32].
Physiology and Growth
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
More detailed information on the T4 superinfection effect on the phage f2 propagation was achieved by using rifamycin and peptide-mapping procedures (Goldman and Lodish 1971). It appeared that the exclusion of the phage f2 required the T4 gene function soon after T4 infection, while synthesis of the f2 coat occurred at a reduced level until 4 min after T4 superinfection and then ceased abruptly, preexisting f2 replicative intermediate RNA and f2 single-stranded RNA were degraded to small fragments, and most f2-specific RNA was released from polyribosomes (Goldman and Lodish 1971). As a consequence, it was suggested that the phage T4 induced the synthesis of an endoribonuclease which specifically degraded f2 RNA and bacterial mRNA.
Exopolysaccharides metabolism and cariogenesis of Streptococcus mutans biofilm regulated by antisense vicK RNA
Published in Journal of Oral Microbiology, 2023
Yuting Sun, Hong Chen, Mengmeng Xu, Liwen He, Hongchen Mao, Shiyao Yang, Xin Qiao, Deqin Yang
Degradation of RNA is a crucial mechanism for regulating gene expression in organisms. Rnc, located upstream of vicR/K/X, affects vicR/K/X gene at the post-transcriptional level [19]. In previous studies, we found that rnc gene regulates carbohydrate transport and metabolism of S. mutans by regulating the expression of ncRNAs (ASvicR and msRNA1657). In addition, RNAse III, encoded by rnc, is a widespread endoribonuclease that binds and cleaves dsRNA. AsRNA allows precise control of the regulatory circuit, which is the key for bacteria to quickly adapt to environmental changes [26,27]. Plenty of studies have confirmed that the virulence factors and adaptability of S. mutans can be regulated by asRNAs, indicating the feasibility of regulating protein function by asRNAs to affect its cariogenesis [28,29].
A comprehensive update of siRNA delivery design strategies for targeted and effective gene silencing in gene therapy and other applications
Published in Expert Opinion on Drug Discovery, 2023
Ahmed Khaled Abosalha, Waqar Ahmad, Jacqueline Boyajian, Paromita Islam, Merry Ghebretatios, Sabrina Schaly, Rahul Thareja, Karan Arora, Satya Prakash
The pharmacokinetic profile of siRNA therapies is highly restricted by several intracellular and extracellular barriers that interfere with the delivery of siRNA successfully to the target site. siRNA is rapidly cleared from the blood with a very short circulation half-life (a few minutes) as a result of many combined factors. Firstly, siRNA is highly retained by the reticulo-endothelial system (RES), endosomes, and lysosomes. Secondly, it is highly vulnerable to degradation by endoribonucleases and exoribonucleases in the plasma and tissues [8,9]. Additionally, siRNAs are mainly excreted by glomerular filtration due to their small size. Moreover, the cellular internalization of siRNA is limited by the electrostatic repulsion between its negatively charged phosphate backbone and the anionic lipid bilayers of cell membranes. Also, the size of siRNA (7–8 nm in length) is larger than the thickness of the cell membrane (5 nm) [10–14]. The above-mentioned barriers provide an explanation for the limited number of approved siRNA therapies currently on the market. It also reveals the urgent need to develop new strategies that can deliver siRNA efficiently to targeted organs with minimum off-target effects.
Virus-associated ribozymes and nano carriers against COVID-19
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2021
Beyza Dönmüş, Sinan Ünal, Fatma Ceren Kirmizitaş, Nelisa Türkoğlu Laçin
Twenty to 30 base length miRNAs are RNAi elements formed by the cleavage of the secondary structured miRNA precursor by endoribonucleases. They inhibit the translation process of mRNA by binding specifically to the ribosome binding site of the mRNA [45]. miRNAs have been used to attenuate viruses that are the main component of attenuated vaccines [46]. These approaches, which have the potential to increase vaccine safety, suggest that they may be useful in controlling viral attenuation and pathogenesis [47,48]. There are identified miRNAs that bind to specific regions of the SARS-CoV-2, SARS-CoV and MERS-CoV genomes and inhibit viral infections caused by the viruses. Additionally, specific miRNAs have been developed against the S protein of SARS-CoV-2 and, in the meantime miRNA inhibitors that target viral miRNAs are also used for this process [49].