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Coronavirus Epidemics and the Current COVID-19 Pandemic
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Aparna Bhardwaj, Prateek Kumar, Shivani Krishna Kapuganti, Vladimir N. Uversky, Rajanish Giri
NSPs are translated from ~20 kb (comprising two-thirds of the whole genome) of replicase genes at the 5′ end. The virus has sixteen non-structural proteins, NSP1-16, which are involved in viral RNA synthesis by forming replication transcription complexes (RTCs). The NSPs manage the complex replication process through their enzymatic activities, including papain-like proteinase (PLpro, NSP3), main protease (3CLpro, NSP5), RNA-dependent-RNA polymerase (RdRp, NSP12), RNA helicase (NSP13), guanine-N-7 methyltransferase (NSP14), endoribonuclease (NSP15), and 2′-O-methyltransferase (NSP16) [40].
Chikungunya virus and Japanese encephalitis virus
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
CHIKV genome has 2 open reading frames (ORF). The 3′ ORF codes for two surface glycoproteins (E1 and E2), a capsid protein (C), and 2 small additional peptides: E3, spliced from the precursor protein PE2, which also codes for E2, and 6k (Figure 15.2a). The 5′ ORF codes for four non-structural proteins (nsP1, nsP2, nsP3, and nsP4), which mediate viral replication. The two ORFs are connected by a noncoding junction region (J). NsP1 serves as an anchor for the replication complex. NsP2 codes for a triphosphatase and cysteine protease involved in protein processing, and nsP3 codes for ADP-ribose 1-phosphate phosphatase. NsP4 codes for the RNA dependent RNA polymerase.
Viral infections
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Sarah Elizabeth Blutt, Mary K. Estes, Satya Dandekar, Phillip D. Smith
The role of IFN-induced antiviral activity in rotavirus infection has been examined in in vivo and in vitro studies. Increasing evidence suggests that type I IFN responses contribute to innate immune-mediated clearance of rotavirus in vitro and in mice. For example, elevated expression of a panel of genes related to type I IFN responses, as well as other pro-inflammatory genes, including interleukin (IL)-8, are detected in gene-profiling studies of rotavirus-infected intestinal epithelial cells. Pretreatment of cultured cells with type I IFNs limits rotavirus infections. Levels of type I and II IFNs are elevated in rotavirus-infected children and animals, and administration of exogenous type I IFN reduces viral replication in mice and disease sequelae in cattle and pigs. Moreover, rotavirus NSP1 suppresses IFN signaling, and mutations in NSP1 that ablate rotavirus's ability to interfere with IFN-related signaling attenuate rotavirus's spread to uninfected cells, further supporting a role for IFN signaling as a potential hindrance to rotavirus infection. While mice deficient in type I and II IFN receptors are able to clear rotavirus, loss of the transcription factor STAT1, which mediates much of the gene expression induced by type I IFN, severely impairs the ability of the host to contain rotavirus.
Recent trends in next generation immunoinformatics harnessed for universal coronavirus vaccine design
Published in Pathogens and Global Health, 2023
Chin Peng Lim, Boon Hui Kok, Hui Ting Lim, Candy Chuah, Badarulhisam Abdul Rahman, Abu Bakar Abdul Majeed, Michelle Wykes, Chiuan Herng Leow, Chiuan Yee Leow
Other proteins chosen for vaccine development includes 3CL hydrolase, nsp1, ORF3a protein and ORF7a protein. 3CL hydrolase is vital for proteolytic maturation of the virus. Short peptides were extracted from this protein as potential epitopes for both CTLs and HTLs in the design of a multiepitope vaccine [88]. The nsp1 may be a major virulence factor for coronaviruses as seen from its functions. It blocks host gene expression by preventing the translation involving 40S ribosomal subunit as well as degrades mRNA of the host cells. In infected cells, the expression of the IFN genes and the host antiviral signalling pathways were impeded [89]. E protein, ORF3a protein, N protein, ORF7a protein and M protein showed a remarkable linkage with the structural integrity and functionality of the virus [90]. ORF3a protein, N protein and M protein are important in the virus replication and function [91]. Figure 1 illustrates the open reading frames (ORFs) in coronavirus genome and a schematic coronavirus structure labelled with structural proteins.
Current status of COVID-19 vaccination: safety and liability concern for children, pregnant and lactating women
Published in Expert Review of Vaccines, 2022
Swagat Kumar Das, Manish Paul, Bikash Chandra Behera, Hrudayanath Thatoi
Bioinformatics has immense importance in the development of an effective vaccine for pharmaceutical applications. Bioinformatics analysis has been employed recently as a substitute for traditional vaccine design methods. Modern bioinformatics analysis is used to design the COVID-19 vaccine more simply and easily by predicting potent epitopic vaccines. Various bioinformatics methods have been used to find the potential epitopes for vaccine formulationBioinformatics techniques can scan viral protein sequences that bind to the Major histocompatibility complex (MHC) in human populations for supertype motifs that could be employed in epitope-based vaccine manufacturing [62]. Sadat et al. [62] used immunoinformatics to assess the conservation and immunogenicity of SARS-CoV-2 proteins to design a preventative vaccine candidate. The genome and protein sequence information for SARS-CoV-2 are available in the NCBI database, and in silico research could be used to predict viral features and epitopes in the pathogen. The structural elucidation and in silico determination of virus effector proteins such as spike protein and nucleocapsid protein aids in the prediction of the B-cell epitope binding site in those effector proteins. Predicted epitopes were evaluated based on antigenicity, surface accessibility, allergenicity, toxicity, hydrophilicity, etc. This approach has proven to accelerate vaccine development significantly [63]. Min et al. [63] looked at the non-structural protein-1 (nsp1) of SARS-CoV-2 from several angles, including (1) substantial sequence similarity to SARS-CoV nsp1, (2)closeness to the 3D fold of the SARS-CoV homolog, (3)functional overview, and differentiation of nsp1 proteins from other coronaviruses (especially SARS-CoV) in controlling host mRNA translation, innate antiviral immunity, and inflammatory response. Poran et al [64] . Performed a structure-based prediction of SARS-CoV-2 vaccine targets using mass spectrometry-based bioinformatics predictors to identify immunogenic T cell epitopes. Murillo et al [65] .reported the COVID-19 pandemic by successfully sequencing the SARS-CoV-2 genome using omics and bioinformatics approaches. They emphasized the significance of gnome, proteome, and metagenome sequence analysis to identify the nature of the virus.
Targeting viral proteins for restraining SARS-CoV-2: focusing lens on viral proteins beyond spike for discovering new drug targets
Published in Expert Opinion on Drug Discovery, 2023
Tao Yang, Si Chun Wang, Linyan Ye, Yasen Maimaitiyiming, Hua Naranmandura
On the other hand, COVID-19 patients with chronic comorbidities (e.g. diabetes, heart or lung diseases, and conditions affecting immune system) are at higher risk for developing severe disease and therefore display much higher mortality, which is also associated with the lack of effective nonvaccine countermeasures to restrain SARS-CoV-2 after the viral entry into host cells of infected individuals [1,2,272–274]. With the abundance of possible targets, there will be more opportunities to exploit novel cost-effective and highly accessible therapeutics to address the above issue. The discovery and development of feasible targets and effective intervention strategies critically depends on the knowledge of molecular and cellular mechanisms of SARS-CoV-2 infections. Accordingly, some viral proteins are considered as priority targets due to the well characterized biochemical functions, presence of druggable chemical binding pockets, degree of conservation among different viruses for old drug repurposing, possible mutations and the possibility for cross-reactivity with host proteins or host substrates, and so on. Thus, beyond the S protein, NSP12 (RdRp), NSP3 (PLpro) and NSP5 (Mpro) are regarded as priority targets than other viral proteins. In fact, other structural and nonstructural proteins of SARS-CoV-2 also play important roles during the progression of virus life cycle, such as hijacking the host cells’ ribosome, viral genome replication and transcription, virion assembly, release and entry into new host cells, as well as compromising host cellular defenses (Table 1). For instance, in the case of non-spike structural proteins, N protein not only functions as the binding partner and stabilizer of the viral genomic RNA, but also suppresses type I IFN production and localizes to the RTC for efficient replication and transcription of viral RNAs [95,96]. E protein participates not only in viral assembly, budding and virulence but also in activating the host inflammasome, making itself a potential target to prevent the cytokine storm in COVID-19 patients [110–113]. As for the nonstructural proteins, once released from the polyproteins by the viral proteases PLpro and Mpro, most of them assemble into the RTC and the larger holoenzyme complex for efficient replication, transcription and processing of viral RNAs [139,162]. NSP1 inhibits the stability and translation of host cell transcripts. NSP14 and NSP16 viral methyltransrefases with their common cofactor NSP10 enables efficient capping of viral RNAs to increase their stability and reduce immunogenicity. The DMVs organized by NSP3, NSP4 and NSP6 compartmentalize viral replication and transcription machinery to evade host immune surveillance. Given the importance of viral protein interactions, disrupting the integrity of the important viral complexes such as DMVs, RTC and the holoenzyme complex via targeting the viral protein interactions with therapeutic peptides or other measures also represent feasible strategies to increase host cellular defense and decrease viral fitness [275–277].