![]() Specifically, the HEs of β-CoVs recognize the 9-O-Ac-neuraminic acids, although certain species bind to the 4-O-Ac forms ( Kim, 2020). Most β-CoVs bind to the 9-O-Ac-neuraminic acids, but mutant strains target 4-O-Ac-neuraminic acids. Bovine CoV (BCoV) and human CoV (HCoV)-OC43 can recognize the 5,9-Ac2-neuraminic acids ( Vlasak et al., 1988) and bear neuraminic acid 9-O-Ac-esterase. The SARS-CoV-2 S-glycoprotein N-terminal domain recognizes the surface entry site, binding to 9-O-Ac-neuraminic acid in a similar manner to CoV HEs as well as influenza C and D HEFs. Murine CoVs esterize the C4-O-Ac ( Smits et al., 2005). However, certain α-CoV and γ-CoV are deficient of the neuraminic acid-O-Ac-esterases but bind to Ac-neuraminic acids or glycolyl-neuraminic acids. The glycoproteins of the HA, HE, S, and HA-esterase-fusion protein (HEF) bind to the host receptor. Therefore, the HE found in the β-CoV genus mediates viral attachment to O-Ac-neuraminic acids. Fusion of S-glycoprotein and HE is important for CoV attachment to neuraminic acid–bearing host receptors ( Tortorici et al., 2019). The neuraminic acid-O-Ac-esterase of HE evolved from the influenza C virus, nidoviruses, and salmon anemia virus (teleost orthomyxovirus). As the first step, the S-glycoprotein of SARS-CoV-2 binds to surfaced O-acetyl (Ac)-neuraminic acids of host cells. The E-, S-, and M-proteins are embedded into the endoplasmic reticulum (ER) membrane and translocated to the ER–Golgi intermediate compartment (ERGIC). Nonstructural protein 3 (Nsp3), Nsp5, Nsp9, and Nsp12 RdRp are enzymes. SARS-CoV-2 viral proteins include RNA-dependent RNA polymerase (RdRp) and hemagglutinin-esterase (HE) enzymes as well as proteins including spike (S), envelope (E), membrane (M), and nucleocapsid (N) ( Figure 1) ( Tu et al., 2020). The COVID-19–causing CoV isolates exhibit 79% identity with the previously named SARS-CoV and 50% identity with the Middle East respiratory syndrome (MERS) virus ( Chan et al., 2020). SARS-CoV-2, belonging to the β-CoV genus, and bat SARS-like CoV-ZXC-21 are similar in their RNA genomes. Most mammals are infected by α-CoV and β-CoV only, while avians and some mammals are infected by δ-CoV and γ-CoV. They are classified into the Riboviria– Nidovirales– Cornidovirineae– Coronaviridae– Orthocoronavirinae–CoV genus (α-, β-, γ-, and δ-CoV). Enveloped CoVs contain positive ssRNA genomes with relatively small RNAs (approximately 30 kb). In addition, SARS-CoV-2 spreads by easy transmission among people, and COVID-19 patients exhibit flu-like symptoms such as fever and cough. SARS-CoV-2 or 2019-nCoV spreads and causes the human life crisis of COVID-19 by infecting the human respiratory tract and causing pneumonia ( Zhou et al., 2020). The coronaviruses (CoVs) target humans and animals with exchangeable infectivity, causing a zoonotic outbreak. Introduction General Virology of Coronaviruses Structure–activity relationship of the anti–SARS-CoV-2 natural compounds is discussed. Artificial intelligence–based computational simulation for drug designation and large-scale inhibitor screening have recently been performed. The molecules are mainly derived from natural products of plant sources by screening or chemical synthesis via molecular simulations. To provide information related to the current development of possible anti–SARS-COV-2 viral agents, the current review deals with the known inhibitory compounds with low molecular weight. ![]() SARS-CoV-2 recognizes O-acetylated neuraminic acids and also several membrane proteins, such as ACE2, as the result of evolutionary switches of O-Ac SA recognition specificities. Vaccine development is being pursued, invoking a better elucidation of the life cycle of the virus. Several drugs are being screened for the ability to block virus entry on cell surfaces and/or block intracellular replication in host cells. Although there is as yet no effective antiviral agent, like tamiflu against influenza, to block SARS-CoV-2 infection to its host cells, various candidates to mitigate or treat the disease are currently being investigated. Researchers exchange information on COVID-19 to enable collaborative searches. Severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2), a β-coronavirus, is the cause of the recently emerged pandemic and worldwide outbreak of respiratory disease. Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkhwan University, Suwon, South Korea. ![]()
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