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The Role of Natural Products in COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Iqra Akhtar, Sumera Javad, Tehreema Iftikhar, Amina Tariq, Hammad Majeed, Asma Ahmad, Muhammad Arfan, M. Zia-Ul-Haq
The solitary and primary protein of coronavirus which is related with RTC (replication Transcription complexes), is known as N protein. It basically joins with the gRNA or guide RNA which is a fundamental step for joining of infectious material to host DNA. It is also a part of ribonucleoprotein complex of the virus, thus playing a role in the structural organization of the virus. For this purpose, this protein has a network of action with other N proteins, M proteins and gRNAs. In CoVs, particularly, N protein is primarily responsible for the encapsidation of viral genome to expose it and to start the viral life cycle. It is considered as a very vital step of coronavirus infection cycle in the host. Therefore, targeting N proteins can get rid of corona infection. Resveratrol is known to target N proteins to get rid of coronavirus infect and it is a natural compound being extracted from a number of plants like can berries, chocolate, Polygonum cuspidatum, Vitis vinifera, etc. [60].
The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
When a gene is active, the chromatin structure loosens to allow access for RNA polymerase to generate an RNA molecule (Figure 2.8). This messenger RNA (mRNA) precursor is then processed for translation into an amino acid sequence. Gene splicing removes introns from the coding sequences to leave a continuous series of exons for translation. Once within the cytosol, mRNA attaches to large ribonucleoprotein particles known as ribosomes. Ribosomes read along mRNA, generating proteins by polymerizing amino acids donated by transfer RNA (tRNA) molecules bearing an appropriate anticodon.
Order Bunyavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The crystal structure of the full-length LASV NP of Josiah (Qi et al. 2010) and AV (Brunotte et al. 2011) strains was solved at a resolution of 1.80 and 2.45 Å, respectively. Separately, crystal structures of functional LASV NP domains were determined. First, the structure of N-terminal domain in complex with single-stranded RNA was shown, suggesting the likely assembly by which viral ribonucleoprotein complexes are organized (Hastie et al. 2011b). Second, the structure of the immunosuppressive C-terminal portion that possesses exonuclease activity with strict specificity for double-stranded RNA substrates was demonstrated (Hastie et al. 2011a). At last, the crystal structure of the homologous C-terminal NP portion was determined for the JUNV (Zhang Yinjie et al. 2013), LCMV (West et al. 2014), and Tacaribe arenavirus (Jiang Xue et al. 2013).
Riboswitches as therapeutic targets: promise of a new era of antibiotics
Published in Expert Opinion on Therapeutic Targets, 2023
Emily Ellinger, Adrien Chauvier, Rosa A. Romero, Yichen Liu, Sujay Ray, Nils G. Walter
High-resolution structures of riboswitches showing their ligand binding pockets as well as their switching regions can be a boon for the development of new antibiotics. Indeed, the previous section showcased how ligand analogs mimic the presence of the essential ligand and derail bacterial gene expression [45,52,65,68,70–73]. However, this strategy has several caveats. First, high concentrations of these drugs are needed as they typically need to reach similar cellular levels as the actual ligand to trigger the riboswitch. Second, these antibiotics only target the RNA motif in isolation, precariously ignoring the critical interactions between the riboswitch and the gene expression machinery of the cell. In fact, essentially all cellular RNAs function as part of ribonucleoprotein complexes. Riboswitches are no exception in that they affect their own transcription and the translation of the downstream genes (Figures 1 and 2). Third, as the example of the lysC riboswitch demonstrates, small ligand mimics can easily have unintended off-target effects that make the clinical result of such compounds difficult to predict. Fourth, mutations in the riboswitch sequence can quickly confer resistance as found in multiple of the cases discussed above.
An overview: CRISPR/Cas-based gene editing for viral vaccine development
Published in Expert Review of Vaccines, 2022
Santosh Bhujbal, Rushikesh Bhujbal, Prabhanjan Giram
CRISPR/Cas gene editing requires two basic components: a Cas enzyme and guide RNA. These components are associated to form a ribonucleoprotein (RNP) complex. CRISPR/Cas system involves different types of Cas enzymes, among them, Cas9 and Cas12a are the most widely used for gene editing. The Cas9 enzyme is a nonspecific type II CRISPR locus, derived spCas9 from Streptococcus pyogenes SF370 [14]. The Cas12a enzyme, also known as Cpf1, is derived from Acidaminococcus sp. (AsCas12a) and Lachnospiraceae bacterium (LbCas12a) [18]. The RNP Complex: Cas protein and gRNA together shown to have a bacterial defense system and also some antiviral effect [19]; this is followed by three steps: 1) Acquisition- in which newly infected viral DNA invades the leading CRISPR locus, 2) Expression- in which the Cas gene is expressed and the CRISPR system is transcribed into a precursor CRISPR-RNA (Pre-crRNA) [20], which subsequently matures into a short mature crRNA with spacers and repeats. 3) Interference- if the virus DNA infects the bacteria again, the CRISPR/Cas9 system interferes, allowing the bacteria to keep a record of the infection and the CRISPR locus to serve as a genetic vaccination card for those bacteria [21,22].
Bilateral Non-Arteritic Anterior Ischaemic Optic Neuropathy in a Patient with a COL4A2 Mutation
Published in Neuro-Ophthalmology, 2022
Kasim Qureshi, Muhammad U. Farooq, Avneet Deol, Christopher Glisson, Philip B. Gorelick
The following year, he suffered two retinal detachments in the right eye, but it was not clear if his vision had changed. His vision remained unchanged from an ophthalmological standpoint for the next 5 years until he had epiretinal surgery in the left eye. Several months postoperatively he presented with blurry vision in the left eye and was found to have a visual acuity of hand motion OD and 20/80 OS with refraction and left optic disc oedema. He then had a ground-level fall, immediately after which he experienced worsening of vision in the left eye. Repeated evaluation showed visual acuity consistent with finger counting OD, and 20/400 with eccentric fixation OS. His pupils were equal in size with an RAPD OD and visual field constriction bilaterally. Funduscopic examination showed pallor of the right optic disc and oedema of the left optic disc. MRI of the orbits was unremarkable. A cerebrospinal fluid analysis found no white blood cells, a normal glucose level, an elevated protein level (59 mg/dL), and unremarkable cytometry. Anti-ribonucleoproteins antibodies were present; however, no further diagnostic study was advised after a rheumatology consultation. He was treated with 3 days of IV methylprednisolone. Twenty-four-hour ambulatory blood pressure monitoring showed blood pressure below 130/80 mmHg during the day with night-time drops of his systolic blood pressure into the 80s. After discharge, whole exome and mitochondrial testing was carried out, and a heterozygous COL4A2 mutation was discovered (Variant: c.3421 C > T p. R1141x).