Introduction to virus structure, classification, replication, and hosts
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
DNA viruses generally use the same strategy employed by the host cell, making use of host machinery (cellular enzymes) that can recognize and transcribe any DNA. However, as indicated earlier, some viruses contain genomic material that consists of RNA. This presents a problem for the virus because host cells do not carry specific enzymes that are able to transcribe from RNA. Therefore, RNA viruses must provide the specific machinery required, either in an already synthesized form present in the infecting virion (e.g., rhabdoviruses and myxoviruses) or in a genomic form that can be translated by the host to produce the necessary enzymes (e.g., picornaviruses). One such enzyme is an RNA-dependent RNA polymerase (RdRp) that transcribes the parental RNA to generate mRNA; alternatively, the genome itself may serve as the mRNA. Retroviruses are unique because they make use of an RNA-dependent DNA polymerase (reverse transcriptase) to copy their RNA genome into a DNA intermediate. This intermediate is then transcribed to generate mRNA.
Enterovirus 68 and Human Respiratory Infections
Sunit K. Singh in Human Respiratory Viral Infections, 2014
The enterovirus ORF can be divided into three regions, P1 through P3 (Figure 31.1). The P1 region encodes for the viral structural proteins VP1 through VP4, arranged 5′ to 3′ as VP4, VP2, VP3, and VP1. VP1 contains type-specific epitopes and has the highest density of neutralization sites. The VP1 sequence, or part of it, is used as the target for molecular typing of enteroviruses.14 The P2 and P3 regions encode for nonstructural proteins, necessary for the viral life cycle. The viral genome gives rise to a viral polyprotein, which is further processed by viral-encoded proteases encoded by segments 2A and 3C, some of which can act in a cis or in a trans form.13 The RNA-dependent RNA polymerase is encoded by 3Dpol.
Medicinal Plants Against COVID-19
Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga in The Covid-19 Pandemic, 2023
In addition to, a flavonoid such as quercetin and saponin was isolated from the T. sinensis leaf extract and liquor ice roots, respectively [80, 81] showed strong antiviral activity against the SARS coronavirus. These compounds stop the cellular attachment and prevent the entry of virus to the human cell. More than 10,000 different compounds like drugs, natural, and synthetic are screened, and these compounds showed the effect results against the SARS coronavirus [82]. Indole alkaloids and were isolated from eucalyptus, L. japonica and Rauwolfia and from chestnut tree, respectively inhibited aescin the SARS coronavirus replication [82]. RNA dependent RNA polymerase is the major enzyme in the replication of SARS coronavirus, which synthesized the positive and negative strand of coronavirus RNA. A toxic steroid-like cardenolides were obtained from the plant and swine testicular cells inhibited the gastro entry of coronavirus [83]. These results showed that toxic cardenolide reduce the 50% RNA copies and suppress the viral replication [83].
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.
A tool with many applications: vesicular stomatitis virus in research and medicine
Published in Expert Opinion on Biological Therapy, 2020
Altar M. Munis, Emma M. Bentley, Yasuhiro Takeuchi
The single-stranded, negative-sense RNA genome of VSV encodes five structural proteins: nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and the viral polymerase [8,9] (Figure 1(a)). The matrix protein is responsible for the formation of the viral core and anchoring of the glycoprotein to the viral membrane enabling the formation of glycoprotein homotrimers [10]. The glycoprotein dictates receptor recognition, cell entry, and viral fusion; thus, it is the major target for the humoral immune response [11]. The RNA-dependent RNA polymerase activity for viral replication takes place in the target cell cytosol and is driven by the complex containing the nucleoprotein, viral polymerase, and phosphoprotein [12]. The viral genes are expressed in a single non-segmented negative strand RNA in order [13]. As the transcriptional activity of the 3ʹ promoter is attenuated at each gene junction, 3ʹ genes of the viral genome are transcribed more abundantly [14] (Figure 1(a)).
Considerations of the effects of commonly investigated drugs for COVID-19 in the cholesterol synthesis pathway
Published in Expert Opinion on Pharmacotherapy, 2021
Juan Luis Gomez Marti, Adam M. Brufsky
Inhibition of the RNA-dependent RNA polymerase (RdRp) has been tried with suboptimal results. Reverse transcriptase inhibitors such as remdesivir have modest efficacy in the treatment of hospitalized patients, it does not clearly result in an increased survival rate [37]. The viral replication machinery of SARS-CoV-2 contains exonuclease-based proofreading, which promotes replication and removal of exogenous nucleotide analogs. Deoxyribose-containing RdRp nucleotide analogs have been shown to be more resistant to the exonuclease proofreading complex than those containing ribose rings such as remdesivir. In this regard, sofosbuvir contains a deoxyribose that exhibits more resistance to this proofreading complex, providing more stability than remdesivir [38]. Trial results evaluating sofosbuvir efficacy against COVID-19 are encouraging. A meta-analysis showed that sofosbuvir in combination with daclatasvir improved time to clinical recovery (HR = 2.04), as well as all-cause mortality compared to control arms (risk ratio = 0.31) [39]. Another trial reported a half-reduction in duration of hospital stay compared to ribavirin (5 vs 9 days, respectively), relative risk of death of 0.17, and a number needed-to-treat for benefit of 3.6 [40].
Related Knowledge Centers
- DNA
- Enzyme
- Poliovirus
- Rna
- Rna Interference
- Virus
- Complementarity
- Rna Polymerase
- Transcription
- Sars-Cov-2