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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7352545","sourcedb":"PMC","sourceid":"7352545","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7352545","text":"1. Introduction\nThe recent coronavirus pandemic crisis is due to viral infection of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), causing uncontrolled inflammatory conditions in the human lung. Soon after the first transmission emergence of SARS-CoV from animals to humans in China in 2003 [1], a genetically evolved beta-coronavirus genus similar to human viruses was discovered in Chinese horseshoe bats (Rhinolophus sinicus) [2]. To date, pneumonia is epidemiologically caused by diverse viruses. For example, adenovirus, influenza virus, Middle East respiratory syndrome virus (MERS-V), parainfluenza virus, respiratory syncytial virus (RSV), SARS-CoV and enteric enveloped CoV can cause pneumonia in human hosts.\nThe World Health Organization (WHO) reported the official terminology of the 2019-Novel Coronavirus (2019-nCoV) on 13 January 2020, and on February 11th, WHO edited the name of the disease caused by 2019-nCoV to Coronavirus Disease-2019 (COVID-19). In academia, the International Committee on Taxonomy of Viruses (ICTV) provided official nomenclature to the virus as SARS-CoV-2 due to the similarity between the novel coronavirus and SARS-CoV [3]. SARS-CoV-2 is spreading and causing a global health-threatening emergency [4]. Researchers have been in a race to develop anti-viral drugs against SARS-CoV-2 even before the WHO declared a worldwide pandemic threatening human lives. Preventive and therapeutic drugs for patients infected with SARS-CoV-2 are yet to be discovered.\nThe CoVs as enveloped forms can also infect the gastrointestinal track (GIT), although most other enteric viruses are naked in morphology [5,6]. CoVs can also rarely infect neural cells [7]. There is, unfortunately, no solid information on how the coronaviruses infect humans and animals with reciprocal infectivity and cause a zoonotic viral outbreak. This is in contrast to influenza viruses, which are known to selectively utilize sialic acid (SA) linkages [8]. Currently, only limited information is available on β-CoVs, such as SARS-CoV and its receptor usage and infectible cell types from different species. Host cell surface O-acetylated SAs are recognized by the lectin-like spike proteins of SARS CoV-2 for the first step of attachment to host cells. Infectious virus interaction with the host cell surface is mediated by sialoglycans as the most important phenomenon in eukaryote-parasite co-evolution. O-GlcNAc, a minor glycan source, is mainly found in the nucleus and cytosol (Figure 1). Apart from the general roles of glycans, CoVs recognize host cells and attach to host cell surface molecules to enter the host cells. For example, activity of the hemagglutinin-esterase (HE) enzyme relies on the typical carbohydrate-binding lectin and receptor-destroying enzyme (RDE) domains. Most β-CoVs target 9-O-acetylated SAs, but certain species have switched to recognizing 4-O-acetyl SA instead [8,9]. Crystallographic data for the molecular structure of type II HE provides an explanation for the switching mechanism to acquire 4-O acetyl SA binding. This event follows the orthodox ligand–receptor interaction (LRI), lectin–carbohydrate interaction (LCI), lectin–glycan interaction (LGI), lectin–sphingolipid interaction (LSI), protein–glycan interaction (PGI), protein–carbohydrate interaction (PCI), and also protein–protein interaction (PPI). Recently, 332 protein candidates were suggested to be SARS-CoV-2-human protein interacting proteins through PPIs. Among these, 66 human proteins, as druggable host factors, were further characterized as possible FDA-approvable drugs [10]. If PPI is involved, however, carbohydrates or glycans may serve as co-receptors or co-determinants. Previous reports suggest that carbohydrates act as receptor determinants in most cases. The general principles of PCI stereochemistry potentiate the SA–ligand switch by way of simple conformational shifts for the lectin and esterase domain. This indicates that our examination of natural adaptation should be directed to how carbohydrate-binding proteins measure and observe carbohydrates, leading to virus evolution toward transitional host tropism.\nThe 9-carbon SAs are mainly animal-specific with anionic sugars attached to terminal sugars. SAs exist in two forms, NeuGc and NeuAc. NeuGc is a differentially modified form of the parental SA form, Neu5Ac. SAs are structurally diverse. For example, several modified SA forms are known for their structures including neuraminic acid (NeuC), N-acetyl neuraminic acid (NeuAc), N-glycolyl neuraminic acid (NeuGc), N,O-diacetyl neuraminic acid (occurs in horses), N,O-diacetyl neuraminic acid (occurs in bovines) and N-acetyl O-diacetyl neuraminic acid (occurs in bovines) (Figure 2). Sialyltransferases (STs) biosynthesize different SA linkages. SA linkage diversity occurs at the α2-3, α2-6, α2-8 or α2-9 to the SA or Gal residues (Figure 3). For example, in formation of α2,3 SA or α2,6 SA structures, α2,3-ST and α2,6-ST utilize substrates such as Galβ-1,4-GlcNAc (Figure 4). The most frequent modification of SAs is O-acetylation at positions of C4, C7, C8 and C9 of SA (Figure 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