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The Viruses
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The structural proteins surrounding viral genomes are arranged into one of two symmetrical forms called capsids that are either helical or icosahedral in shape. The simplest viruses consist of a rodlike helix or coil of RNA closely associated with structural proteins. There are no known animal viruses lacking an outer envelope and thus naked helical morphology; however, an example of one found in plants is the tobacco mosaic virus. The simplest animal viruses are naked icosahedral viruses such as the parvoviruses. They consist of a DNA or RNA strand within a protein shell called a capsid (Figure 16.1 A). The capsid consists of a structure created by the regular arrangement of structural subunits called “capsomeres.” Each capsomer is composed of a set of viral structural proteins. The other major forms of viruses are the enveloped icosahedral viruses such as the herpesviruses or the enveloped helical viruses such as the rhabdoviruses (Figure 16.1 B and 16.1C). Viral nucleic acid strands with bound proteins generally have helical morphology while viral genomes within a capsid structure also referred to as a nucleocapsid are characteristically icosahedral in morphology.
Order Articulavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
When Mena et al. (1996) expressed all ten influenza virus-encoded proteins in the COS-1 cells, as mentioned earlier, the transfected CAT RNAs were rescued into influenza VLPs that were budded into the supernatant fluids. The released VLPs not only resembled influenza virions but also transferred the encapsidated CAT RNA to the model MDCK cell cultures. Such VLPs required trypsin treatment to deliver the RNA to fresh cells and could be neutralized by a monoclonal antibody specific for the influenza A virus HA. These data indicated that influenza VLPs were capable of encapsidating a synthetic RNA, which could be delivered to fresh cells for expression of foreign genes of interest. For other virus vectors, it has been shown that such “vector VLPs” encapsidated nucleic acids by utilizing the ability of viral structural proteins to recognize specific encapsidation signals within the nucleic acid sequences.
SARS-CoV-2 Morphology, Genomic Organisation and Lifecycle
Published in Srijan Goswami, Chiranjeeb Dey, COVID-19 and SARS-CoV-2, 2022
Srijan Goswami, Ushmita Gupta Bakshi
The RNA dependent RNA polymerase copies the +ssRNA starting from the 3' end up until it reaches the first transcription regulatory sequence (TRS), for example, the gene for nucleocapsid designated as N in Figure 2.13. From that TRS (corresponding to N gene), the viral polymerase jumps to the 5' end and copies the leader sequence, yielding a small negative mRNA (of N gene). Again, the viral polymerase starts copying from the 3' end of +ssRNA, and this time it ignores the first TRS (i.e., the N gene) and instead recognises the second TRS, for example, the gene for membrane protein designated as M. From that TRS (corresponding to the M gene), the viral polymerase jumps to the 5' end and again copies the leader sequence, yielding another small negative mRNA (of M gene). That means everything in between the TRS and leader sequence (L) is completely omitted. This discontinuous transcription process continues until all the different types of negative subgenomic mRNAs are synthesised that are important for the viral lifecycle. All these newly synthesised negative mRNAs of varying size come from the same strand of original RNA, therefore, they are called subgenomic. The negative subgenomic mRNAs are then converted back to respective positive subgenomic mRNAs, and these are an actual form of subgenomic mRNA that encodes viral structural proteins. These viral structural proteins are combined with original genomic sense genomic RNA to make progeny.
Locked and loaded: engineering and arming oncolytic adenoviruses to enhance anti-tumor immune responses
Published in Expert Opinion on Biological Therapy, 2022
E1A is the master regulator of the viral life cycle. E1A encodes the first viral proteins expressed after infection. Upon DNA entry into the nucleus, typically abundant and ubiquitous host transcription factors bind to the E1A enhancer and promoter to activate its expression without any input from viral proteins. E1A proteins then activate the expression of downstream early genes E1B, E2, E3, and E4 that are essential for viral replication, repression of host cell transcription and translation, and inhibition of host cell antiviral responses [29]. The transition from the intermediate phase to the late phase is dictated by the activation of the major late promoter and the expression of L1-L5 regions of the genome via the MLTU. The expression of these late proteins is mediated by L4-33 K, an RNA splicing factor whose expression is driven by the L4 promoter activated by E1A, E4-ORF3, and IVa2 [30,31]. This stepwise early to late gene expression pattern is evolutionarily developed in most large DNA viruses. It allows efficient virus production by first inhibiting host antiviral responses, amplifying viral DNA, and then producing viral structural proteins for the virion assembly [29].
In quest of a new therapeutic approach in COVID-19: the endocannabinoid system
Published in Drug Metabolism Reviews, 2021
Ondine Lucaciu, Ovidiu Aghiorghiesei, Nausica Bianca Petrescu, Ioana Codruta Mirica, Horea Rareș Ciprian Benea, Dragoș Apostu
SARS-CoV-2 belongs to the Coronavirinae family, presenting the largest genome among RNA viruses. This virus is an enveloped, positive-sense RNA virus, with spike-like projections on the surface (Jin et al. 2020). Viral replicase/transcriptase function is encoded in two-thirds of the genome, while the other third encodes viral structural proteins. The genome is packed into a helical nucleocapsid protected by a lipid bilayer. Based on their genomic structure, Coronaviruses are divided into four groups: α, β, γ, and δ. The first two types of coronaviruses infect only mammals (Rabi et al. 2020). SARS-CoV-2 is a β coronavirus. Four proteins are present in coronaviruses: nucleocapsid (N), envelop (E), membrane (M), and spike (S). The last-mentioned protein determines the host tropism, being the leading mediator of viral entry and it is formed out of transmembrane trimetric glycoprotein (Bosch et al. 2003). This protein has two subunits: S1 and S2, S1 is responsible for the process of binding to the host cell, and S2 for the fusion of the cell and virus membrane. Li et al. 2003 demonstrated that Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the SARS coronavirus. ACE2 is a type I integral membrane protein, a mono-carboxypeptidase that hydrolyzes angiotensin II. This protein is highly expressed on lung epithelial cells, in the heart, ileum, kidneys, and bladder (Zou et al. 2020).
An overview on the use of antivirals for the treatment of patients with COVID19 disease
Published in Expert Opinion on Investigational Drugs, 2021
Maricar Malinis, Dayna McManus, Matthew Davis, Jeffrey Topal
SARS-CoV-2 is a single-stranded RNA-enveloped virus with a spike protein, similar to other coronaviruses, which facilitates viral entry into the host cell. Figure 1 illustrates the life cycle of the virus [2]. The spike protein engages with the angiotensin-converting enzyme 2 (ACE2) receptor, found in various organs such as the heart, lung, gastrointestinal tract, and kidneys. After the binding process, the fusion of the viral membrane and host cell occurs [3]. The host cell type 2 transmembrane serine protease (TMPRSS2) primes the spike protein ensuing its cleavage and conformational change that allows viral entry [4,5]. SARS-CoV-2 is internalized via endocytosis, and subsequently, its genomic material is released from the endosome into the cytoplasm. The viral RNA is translated into viral polyproteins by a viral replicase complex [6]. Subsequently, the RNA-dependent RNA polymerase synthesizes viral RNA and viral structural proteins are produced. After the viral assembly, mature virions are released by exocytosis [6,7]. Steps in this viral life cycle can be potential drug targets to inhibit viral replication. Investigational agents and repurposed drugs with their corresponding mechanisms of action were summarized in Table 1.