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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
ORF8 is an immune evasion protein that has evolved very rapidly. The ORF8 of SARS-CoV-2 is very distinct from ORF8 of SARS-CoV, with a sequence similarity of less than 20%. ORF8 of SARS-CoV-2 interrupts IFN-I signaling and decreases the level of MHC-I cells [51]. Figure 1.3C presents structures of structural proteins, and Figures 1.3D, 1.3E, and 1.3F show three of the accessory proteins of SARS-CoV and SARS-CoV-2. Two of the accessory proteins of SARS-CoV, ORF3b, and ORF6, have been reported to act as interferon antagonists and inhibit the expression downstream, i.e., signaling for innate immunity in host cells [52]. As interferon antagonists, they block the movement of STAT1 to the nucleus. STAT1 is a signal mediator of both IFN-α and IFN-β and acts as a transactivator. Thus because of viral interference, the IFN pathway is downregulated [53]. ORF7a is a type I transmembrane protein, which induces apoptosis of host cells by inhibition of translation and suppression of the cell cycle [54]. ORF9b is translated from the bicistronic mRNA via leaky ribosome scanning and plays an important role in viral particle packaging [55].
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).
Human bronchial-pulmonary proteomics in coronavirus disease 2019 (COVID-19) pandemic: applications and implications
Published in Expert Review of Proteomics, 2021
Heng Wee Tan, Yan-Ming Xu, Andy T. Y. Lau
Genes encoding for the coronavirus accessory proteins are dispersed in between (and sometimes overlapping) the structural genes [87]. These accessory proteins are poorly characterized structurally, and their exact functions remain largely mysterious – it is postulated that they may play a role in viral pathogenesis, evolution, and adaptation to the human host [87]. Some of these accessory proteins (e.g. ORF3a, ORF6, and ORF9b) are conserved in SARS-CoV-2 and SARS-CoV, while others appear to be species-specific. For example, ORF10 proteins are found in the proteome of SARS-CoV-2 and animal coronaviruses including pangolin and bat, but not in the SARS-CoV [88]. Interestingly, ORF10 of pangolin-coronaviruses showed 97.3–99.2% sequence similarity to SARS-CoV-2 ORF10, but their ORF10 proteins are expected to have very different physicochemical, structural, and immunological properties [88,89]. The pangolin is the suspected intermediate host of SARS-CoV-2. Therefore, based on the peptide signatures obtained from the main structural proteins of SARS-CoV-2 and other coronaviruses, researchers are able to detect and track the origin of SARS-CoV-2. For example, using a MS/MS proteomics approach, Gouveia et al. [90] identified a shortlist of 14 peptides that can be used for the detection of SARS-CoV-2 based on their species-specificity and other characteristics. In another study, a MS-based assay was established to detect the nucleoprotein peptides of SARS-CoV-2 directly from suspected COVID-19 patients [91].
COVID-19 and human reproduction: A pandemic that packs a serious punch
Published in Systems Biology in Reproductive Medicine, 2021
George Anifandis, Helen G. Tempest, Rafael Oliva, Grace M. Swanson, Mara Simopoulou, Charles A. Easley, Michael Primig, Christina I. Messini, Paul J. Turek, Peter Sutovsky, Steve J. Ory, Stephen A. Krawetz
Given that mammalian target proteins are present in ACE2-expressing testicular cells it is possible that their interactions with respective viral proteins are of biological and clinical importance (www.proteinatlas.org; Djureinovic et al. 2014; Uhlen et al. 2015). For example, nsp12 is the catalytic subunit of SARS-CoV-2’s RNA dependent RNA polymerase (Peng et al. 2020). The nsp12’s abnormal presence in mammalian cells might alter the activities of SBNO1 and TYSND1 that are involved in WNT signaling and peroxisome function, respectively. The former is relevant for spermatogonial stem cell differentiation (Yoshida 2018) and the latter is critical for sperm maturation (Mizuno et al. 2013). Also, nsp13 is an RNA helicase that via its interaction with PRKAR2A, might interfere with cAMP-dependent signaling important for lipid and glucose metabolism and hormonal regulation of Sertoli cells (Ni et al. 2020; Shu et al. 2020). The orf9b is a negative regulator of mitochondrial function and may also interfere with germ cell/Sertoli cell communication by recruiting PTBP2 into a bipartite protein complex (Shi et al. 2014; Hannigan et al. 2017). Finally, M is a structural component of the viral envelope that, by binding REEP6 could alter protein transport pathways important for spermiogenesis and oocyte fertilization (Devlin et al. 2020; Satarker and Nampoothiri 2020). In summary, it seems that viral proteins interact with human protein-targets that could exert their action at any time during the entire male reproductive cycle from spermatogonial stem cell differentiation to a spermatozoa’s ability to fertilize an oocyte. Notably, in a recent study, it was proposed that SARS-CoV-2 may also be a sexually transmitted virus as other viruses, like Ebola and Zika (Fei et al. 2020).