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Nanomedicine Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Saima Zulfiqar, Zunaira Naeem, Shahzad Sharif, Ayoub Rashid Ch., M. Zia-Ul-Haq, Marius Moga
These produced polyproteins generate 15 to 16 non-structural proteins via autoproteolytic cleavage. These nonstructural proteins are responsible for some significant activities like: nsp12 can encode the RNA-polymerase activity which is RNA-dependent [23];nsp3, nsp4, and nsp6 through spherules or DMV (double-membrane vesicle) can mediate the rearrangement of cell-membrane;nsp3 and nsp5 can encode the protease-PLpro just like papain [37] and major activities of protease-Mpro sequentially [38, 39].
Rotavirus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Lijuan Yuan, Tammy Bui, Ashwin Ramesh
Rotaviruses belong to the Reoviridae family of viruses, which are characterized by a segmented double-stranded RNA (dsRNA) genome encapsulated within a nonenveloped, triple-layered icosahedral capsid. The first visualization of RV under electron microscopy (EM) of negatively stained fecal extracts revealed wheel-like particles, with a diameter of 70 nm.4,5 This led to it being named rotavirus—where “rota” was derived from the Latin word for “wheel.”6 It was later confirmed using electron cryomicroscopy that the fully infectious virion, together with its protruding spike domain,7 spans a diameter of approximately 100 nm.8 The RV genome consists of 11 segments that encode for six viral structural proteins (VP1–VP4, VP6, and VP7) and six nonstructural proteins (NSP1–NSP6). Each of the genome segments encodes one protein (monocistronic), except for segment 11 which encodes two proteins (NSP5 and NSP6).9
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
NSP1 is the cleavage product of the action of PLpro from the divergent 5′ end sequence. The physiological function of SARS-CoV-2 NSP1 is not yet fully understood. Figure 1.4A shows the crystal structure of the NSP1 N-terminal region (polypeptide of residues 13–128) of SARS-CoV [56]. It blocks the translation in the host by binding to the ribosomal 40S subunit. Correlated computational and experimental studies showed the C-terminal of NSP1 as disordered, but it gains helical conformation when provided with organic solvents in its surrounding environment [57]. Much less is known about the NSP2 of SARS-CoV and SARS-CoV-2, but NSP2 has been suggested to suppress the host immune system, such as NSP1, and to interact with NSP3 [58]. NSP3 is a viral papain-like protease (PLpro) with cysteine in its active site (Figure 1.4B). PLpro cleaves polyproteins for the formation of mature proteins by identifying a specific motif sequence (LXGG) between proteins. It triggers the host innate immunity by its inhibitory action on the production of cytokines and chemokines [59]. It also interacts with NSP4 (predicted to be a transmembrane protein) along with NSP6 (which is also a transmembrane protein) to form a complex to modify the ER into double-membrane vesicles [58]. NSP5 is the main protease (Mpro), also known as 3C-like protease (Figure 1.4C). It is one of the vital enzymes for viral replication and transcription. It cleaves 11 conserved sites on the proteome after its autolytic cleavage from pp1a and pp1ab [60]. These proteases are centrally placed targets for antiviral drugs. However, it was recently reported that viruses mutate at certain hotspots in NSP5, resulting in impaired vaccine efficacy [61]. NSP11 is a small disordered protein of only 13 amino acids, with disordered-like characteristics even in the presence of some natural osmolytes [62].
Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy
Published in Expert Opinion on Therapeutic Targets, 2021
James Michael Brimson, Mani Iyer Prasanth, Dicson Sheeja Malar, Sirikalaya Brimson, Premrutai Thitilertdecha, Tewin Tencomnao
PB28 has an affinity for both the sigma-1 receptor and sigma-2/TMEM97 (0.38 and 0.68 nM, respectively) [132], acting as an antagonist of the sigma-1 and agonist of the sigma-2. PB28 has been identified as a drug that can lessen the severity of SARS-CoV-2 infection [61]. PB28 has been reviewed in much detail regarding its role in preventing the severity of SARS-CoV-2 infection [133]. One compelling hypothesis that could explain PB28’s SARS-CoV-2 protective properties involves the InsP3 receptor and the SARS-CoV-2 NSP6 protein. The NSP6 protein locates at the ER and modulates autophagy [134], favoring further infection by preventing the delivery of viral components to the lysosome by the autophagosome. The binding of PB28 to the Sigma-InsP3 receptor complex results in modulation of NSP6 activity at the ER. PB28 could induce NSP6 binding while also inducing oxidative stress via lysosomal leakage, which in turn activates cytoprotective autophagosome activation [135].
Fifteen years of experience with the oral live-attenuated human rotavirus vaccine: reflections on lessons learned
Published in Expert Review of Vaccines, 2020
Priya Pereira, Volker Vetter, Baudouin Standaert, Bernd Benninghoff
RVs belong to the Reoviridae family, and are classified into 10 genetically distinct groups/species (A–J); however, group A RV is the most common cause of human disease [14]. The RV RNA encodes 6 structural viral (VP1-VP4, VP6, VP7) and 6 non-structural proteins (NSP1-NSP6). RV strains are usually genotyped based on differences in the RNA sequences encoding 2 of the VPs (VP7 and VP4). There are six predominant circulating group A RV strains (G1P [8], G2P [4], G3P [8], G4P [8], G9P [8] and G12P [8] genotypes), that are causing >90% of the severe RV disease cases [14,15]. RV epidemiology is sero-diverse across settings and constantly fluctuating both in the pre- and post-vaccination eras. Surveillance is ongoing to understand these changes.
Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection
Published in Gut Microbes, 2022
Julia A. Brown, Katherine Z. Sanidad, Serena Lucotti, Carolin M. Lieber, Robert M. Cox, Aparna Ananthanarayanan, Srijani Basu, Justin Chen, Mengrou Shan, Mohammed Amir, Fabian Schmidt, Yiska Weisblum, Michele Cioffi, Tingting Li, Florencia Madorsky Rowdo, M. Laura Martin, Chun-Jun Guo, Costas A. Lyssiotis, Brian T. Layden, Andrew J. Dannenberg, Paul D. Bieniasz, Benhur Lee, Naohiro Inohara, Irina Matei, Richard K. Plemper, Melody Y. Zeng
Our work suggests a gut-lung axis during SARS-CoV-2 infection that may dictate disease severity by regulating viral entry, adaptive immunity, and coagulation response. In the context of COVID-19, several studies have found altered microbiomes following SARS-CoV-2 infection.32–36 However, due to the high variability of the human microbiomes, which may have been influenced by the infection and medications in COVID-19 patients, controlled animal studies might help define the role of the gut microbiome in host response to SARS-CoV-2 infection. Interferon signaling is efficiently suppressed by at least 13 components of the SARS-CoV-2 genome, including spike protein, the nucleocapsid proteins nsp1 and nsp6, and accessory proteins ORF3b and ORF6.37 Poor T cell responses, characterized by low numbers of IFNγ+ CD4+ T cells and cytotoxic SARS-CoV-2-specific CD8+ T cells, are associated with severe or fatal COVID-19 outcomes.38 Enhanced megakaryopoiesis and excessive influx of neutrophils into the lung are further hallmarks of severe COVID-19.8,26 SCFAs modulate the immune response in many ways, including promoting regulatory and effector T cell development, T cell memory, and plasma cell differentiation.13,39–41 Here, we found that SCFAs enhance antiviral T cell responses, spike-specific B and T cells, and antibody neutralization following intranasal infection with a VSV pseudovirus expressing the spike protein. Importantly, we observed these phenotypes in hACE2 mice, in which human Ace2 expression is not affected by SCFA treatment, and in wild-type mice inoculated with heat-inactivated virus, suggesting that the enhancement of immune responses that we observed is independent of the effect of SCFAs on ACE2-mediated viral entry, and may thus have an effect on other disease states as well.