China
Africa
Explore chapters and articles related to this topic
Replication
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
As it follows from Chapters 13 and 16, the specific RNA synthesis process is tightly coupled with the phage RNA translation, and the whole replication cycle is fully subjected to the translational control. First, both replication and translation share common interchangeable components, namely, the ribosomal protein S1, the elongation factors EF-Tu and EF-Ts, and the Hfq chaperone. Second, RNA replication occurs simultaneously with RNA translation on the nascent RNA plus strand chains. Third, the parameters of the whole replication cycle are determined by special regulatory mechanisms, namely, the polarity phenomenon and the controlling action of the two repressor complexes I and II that were described in Chapter 16.
Cancer-Causing Viruses
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Satya P. Gupta, Vertika Gautam
HCV is a single-stranded RNA virus of the Hepacivirus genus in the Flaviviridae family. It is the only positive-stranded RNA virus among the human oncogenic viruses. The length of the HCV genome is approximately 9.6 kb with a polyprotein of about 3,000 amino acids encoded in it. This polyprotein precursor is cleaved by cellular and viral proteases into three structural proteins (core, E1, E2) and seven nonstructural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) (Lindenbach and Rice 2005). Both envelope proteins (E1 and E2) are highly glycosylated and important in cell entry. E1 serves as the fusogenic subunit, and E2 acts as the receptor-binding protein. Of the nonstructural proteins, the NS5B protein (65 kDa) is the viral RNA-dependent RNA polymerase, which has the key function of replicating the HCV’s viral RNA by using the viral positive RNA strand as its template. NS5B catalyzes the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication (Moradpour et al. 2007; Rigat et al. 2010).
Multi-stage structure-based virtual screening approach towards identification of potential SARS-CoV-2 NSP13 helicase inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mahmoud A. El Hassab, Wagdy M. Eldehna, Sara T. Al-Rashood, Amal Alharbi, Razan O. Eskandrani, Hamad M. Alkahtani, Eslam B. Elkaeed, Sahar M. Abou-Seri
Among the above-mentioned targets, the helicase enzyme plays an essential role in the viral RNA replication in concert with the replication-transcription complex (NSP7/NSP8/NSP12)6. It has two reported functions, firstly it catalyses the unwinding of viral double-stranded RNA in a 5′ to 3′ direction, and secondly, it has a vital role in the formation of the viral 5′ mRNA cap7,8. Despite its crucial role, the helicase enzyme stands as an under-represented target, taking less attention than both RNA-dependent RNA polymerase and the Mpro. Nevertheless, targeting the helicase enzyme could open a new horizon for the combined therapy against SARS-CoV-2 virus that could easily overcome any emerged resistance. Moreover, the helicase enzyme is highly conserved amongst different Coronavirus strains as evidenced by a single amino acid mutation between SARS COV and SARS-CoV-29. Thus, SARS-CoV-2 helicase inhibitors could serve as an effective broad-spectrum antiviral against current and future COVID infections9. To this end, our team was triggered to implement computational approaches to accelerate the drug discovery of SARS-CoV-2 helicase inhibitors.
The vital role of animal, marine, and microbial natural products against COVID-19
Published in Pharmaceutical Biology, 2022
Aljawharah A. Alqathama, Rizwan Ahmad, Ruba B. Alsaedi, Raghad A. Alghamdi, Ekram H. Abkar, Rola H. Alrehaly, Ashraf N. Abdalla
The 5′ cap end of the viral genome has a leader series and untranslated region (UTR) composed of multiple regions. These are crucial to the formation of the many stem loop structures that are necessary for RNA replication and transcription. At the accent gene there are transcriptional regulatory sequences (TRSs) composed of a specific portion of 50–100 nucleotides required for the expression of each of those genes. The RNA structures needed to replicate and synthesize RNA are located in the 3′ UTR. The two-third (20 kilobases) of the genome consists of replicase genes known as open reading frames 1a and ab (ORF1ab), and encoded non-structural proteins (nsp), whereas the remaining region of the total viral genome (10 kilobases) encodes structural and accent proteins such as structural proteins involving spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Furthermore, the structural genes such as ORF3a, ORF3d, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF14, and ORF10 genes encode nine accessory proteins. The CoV genome is structured in the following order: 5′-leader-UTR-ORF-S-E-M-N-accessory proteins genome-3′ UTR-poly (A) tail with accessory genes interspersed among the structural genes at the 3′ end of the genome (Pal et al. 2020; Yadav et al. 2021).
Hepatitis D virus (HDV): investigational therapeutic agents in clinical trials
Published in Expert Opinion on Investigational Drugs, 2022
The virus enters the hepatocytes, sheds the HBsAg envelope, and is transported to the nucleus using a nuclear localization signal intrinsic to L-HDAg [35,36]. Notably, HDV hijacks the host RNA polymerase II for transcription; both S-HDAg and L-HDAg are crucial, and act dichotomously, during this process; S-HDAg is promotes HDV RNA replication, whereas L-HDAg has an inhibitory effect on it and promotes viral assembly prior to exocytosis [37]. Replication of the RNA occurs via a RNA dependent RNA replication double rolling circle mechanism, by utilizing the host cell RNA polymerase. During the course of HDV replication, three distinct RNAs are generated including genomic RNA, antigenomic RNA, and a shortened antigenomic RNA containing the ORF for HDAg [38,39]. The editing of this last RNA by cellular adenosine deaminase acting on RNA (ADAR) determines translation to either S-HDAg or L-HDAg, to promote replication or viral packaging, respectively [40]. Multimeric RNA transcripts are generated using the circular genome and are later cleaved and ligated by RNA sequences termed ribozymes. The cleaved multimers are transcribed into monomeric antigenomic RNA, which serves as a replicative intermediate to produce more circular genomic HDV RNA [41,42]. This circular genome can enter into another replication cycle, undergo transcription of HDV mRNA, or be transported for cytoplasmic HDV virion production [43].