Global analysis of lysine acetylation in the brain cortex of K18-hACE2 mice infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected hundreds of millions of people all over the world and thus threatens human life. Clinical evidence shows that SARS-CoV-2 infection can cause several neurological consequences, but the existing antiviral drugs and vaccines have failed to stop its spread. Therefore, an understanding of the response to SARS-CoV-2 infection of hosts is vital to find a resultful therapy. Here, we employed a K18-hACE2 mouse infection model and LC-MS/MS to systematically evaluate the acetylomes of brain cortexes in the presence and absence of SARS-CoV-2 infection. Using a label-free strategy, 3829 lysine acetylation (Kac) sites in 1735 histone and nonhistone proteins were identified. Bioinformatics analyses indicated that SARS-CoV-2 infection might lead to neurological consequences via acetylation or deacetylation of important proteins. According to a previous study, we found 26 SARS-CoV-2 proteins interacted with 61 differentially expressed acetylated proteins with high confidence and identified one acetylated SARS-CoV-2 protein nucleocapsid phosphoprotein. We greatly expanded the known set of acetylated proteins and provide the first report of the brain cortex acetylome in this model and thus a theoretical basis for future research on the pathological mechanisms and therapies of neurological consequences after SARS-CoV-2 infection.

Porcine Epidemic Diarrhea Virus Antagonizes Host IFN-λ-Mediated Responses by Tilting Transcription Factor STAT1 toward Acetylation over Phosphorylation To Block Its Activation.

Porcine epidemic diarrhea virus (PEDV) is the main etiologic agent causing acute swine epidemic diarrhea, leading to severe economic losses to the pig industry. PEDV has evolved to deploy complicated antagonistic strategies to escape from host antiviral innate immunity. Our previous study demonstrated that PEDV downregulates histone deacetylase 1 (HDAC1) expression by binding viral nucleocapsid (N) protein to the transcription factor Sp1, inducing enhanced protein acetylation. We hypothesized that PEDV inhibition of HDAC1 expression would enhance acetylation of the molecules critical in innate immune signaling. Signal transducer and activator of transcription 1 (STAT1) is a crucial transcription factor regulating expression of interferon (IFN)-stimulated genes (ISGs) and anti-PEDV immune responses, as shown by overexpression, chemical inhibition, and gene knockdown in IPEC-J2 cells. We further show that PEDV infection and its N protein overexpression, although they upregulated STAT1 transcription level, could significantly block poly(I·C) and IFN-λ3-induced STAT1 phosphorylation and nuclear localization. Western blotting revealed that PEDV and its N protein promote STAT1 acetylation via downregulation of HDAC1. Enhanced STAT1 acetylation due to HDAC1 inhibition by PEDV or MS-275 (an HDAC1 inhibitor) impaired STAT1 phosphorylation, indicating that STAT1 acetylation negatively regulated its activation. These results, together with our recent report on PEDV N-mediated inhibition of Sp1, clearly indicate that PEDV manipulates the Sp1-HDAC1-STAT1 signaling axis to inhibit transcription of OAS1 and ISG15 in favor of its replication. This novel immune evasion mechanism is realized by suppression of STAT1 activation through preferential modulation of STAT1 acetylation over phosphorylation as a result of HDAC1 expression inhibition. IMPORTANCE PEDV has developed sophisticated evasion mechanisms to escape host IFN signaling via its structural and nonstructural proteins. STAT1 is one of the key transcription factors in regulating expression of ISGs. We found that PEDV and its N protein inhibit STAT1 phosphorylation and nuclear localization via inducing STAT1 acetylation as a result of HDAC1 downregulation, which, in turn, dampens the host IFN signaling activation. Our study demonstrates a novel mechanism that PEDV evades host antiviral innate immunity through manipulating the reciprocal relationship of STAT1 acetylation and phosphorylation. This provides new insights into the pathogenetic mechanisms of PEDV and even other coronaviruses.

Trifluoroacetic Anhydride as Acylating Agent and Dehydrant in One-pot Synthesis of Nirmatrelvir

Nirmatrelvir is an effective ingredient in the anti COVID-19 drug Paxlovid. There were two key steps in the original synthetic route, which involved trifluoroacetylation and dehydration. A facile and efficient synthesis of nirmatrelvir is described in this work. Intermediate 7 was converted to nirmatrelvir in one-pot synthesis with trifluoroacetic anhydride. In addition, the condensation and deprotection conditions were optimized. The yield of nirmatrelvir produced from 1raised from 51.6% to 72.5%. © 2023,Cleveland Clinic Journal of Medicine.All Rights Reserved.

Interest of drug checking supply: Results of 3 years of activity in Geneva

Aim: Swiss drug policy aims to reduce recreational drug consumption and its negative consequences. The strategy is based on a four pillars concept: prevention, therapy, harm reduction and repression. Among harm reduction programs drug checking (DC) facilities have emerged, allowing drug users to check the presence of adulterants or other non-expected substances, and to gain information concerning the purity of the product, without encouraging drug consumption. In 2019, one DC opened in Geneva (Switzerland) after receiving an authorization from the Federal Office of Public Health, and the results of 3 years of activity are presented. Method(s): Drug users brought samples anonymously to DC. Samples were send to the laboratory for analyses, and results are transmitted to DC, where drug users could obtained and discussed the results. Samples were dissolved in methanol, and a general unknown screening was performed by using gas chromatography coupled to mass spectrometry (GC-MS) directly and after acetylation. Depending of the substances, quantitative analyses were performed by using GC-MS, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), or liquid chromatography coupled to diode array detector (LC-DAD). Result(s): A total of 883 samples were analyzed from June 2019 to April 2022. The majority of samples were powders (67%), tablets (11%), plants (8%), and blotting papers (6%). For 71 samples (8%) the detected substances did not correspond to those announced by consumers, and in 23 samples (3%), no psychoactive substances were detected. Cocaine was detected in 290 samples (33%), with a median purity of 75%. In these samples, 11% contained also levamisole, 11% caffeine, and 7% phenacetin. Sympathomimetics were detected in 278 samples (31%). MDMA (16%), amphetamine (4.8%), 3-MMC (3.3%), 2C-B (2.6%), and 4-MMC (1.4%) were the most detected substances in this group of substances. MDMA was detected in powder specimen with a median purity of 85%, and in tablet form with a median amount of 133 mg (range: 3-320 mg). More rarely, methamphetamine, MDEA, 6-APB, 2C-D, 2C-E, BOD, 2-Br-4,5-DMPEA, DOB, DOC, DOM, MBDB, 3-FA, 5-MMPA, 5-MAPB, and 4-CMC were observed. Cannabinoids were detected in 84 samples (9.5%), and among these samples, 11 contained synthetic cannabinoids [5-Fluoro-MDMB-PINACA (3 cases);MDMB-4en-PINACA (8 cases)]. LSD and other hallucinogenic substances (1cP-LSD, psilocin, DMT, 4-ACO-DMT, 4-HO-MET) were detected in 85 samples (9.6%). Ketamine was detected in 68 cases (7.7%), with a median purity of 76%. Heroin was detected in 64 cases (7.2%), with a median purity of 20%. Benzodiazepines (alprazolam or etizolam) were detected in 7 cases (0.8%). The DC activity reached out to consumers who were not yet connected to prevention structures. The prevalence of the detected substances in the DC samples analyzed confirmed roughly what was known about the local market for illicit substances. However, some unexpected results were observed, such as the number of samples containing ketamine, or some new psychoactive substances. Interestingly, a couple of months after the beginning of COVID pandemic, 2 synthetic cannabinoids never detected before in Western Switzerland were observed, showing the interest of the DC facility in a harm reduction strategy, and more generally for public health prevention. Conclusion(s): Knowledge concerning the market of illicit psychoactive substances is complex and often difficult to assess. In this context, the analyses carried out for the Geneva DC have demonstrated a definite interest in better knowing and understanding the dynamics of the illicit substance market, complementing other information from police and customs seizures, wastewater analyses, used needle analyses, suspected DUID case analyses, clinical toxicology case analyses and postmortem case analyses. Copyright © 2022

Pharmacological Activity and Applied Research of Heparin and its Derivatives

Heparin is a kind of glycosaminoglycan drug with a complex structure, which is a mixture of polysaccharides with different chain lengths composed of hexuronic acid, aminohexose and its derivatives.Hexuronic acids are L-aduronic acid and D-glucuronic acid, aminohexose is α -D-glucosamine, and the modification of derivatives includes sulfation and acetylation.As a natural biomacromolecule, heparin has a variety of biological activities.It has been discovered for more than a hundred years and has good anticoagulant effect, which is clinically the first choice for anticoagulant and prevention and treatment of thromboembolic diseases.It has been discovered that there are more than one hundred functional proteins that interact with heparin.Heparin can bind to a variety of proteins and exert a variety of biological activities such as anticoagulant, anti-inflammatory, antiviral, and anti-tumor. The anticoagulant mechanism of heparin has been explained in detail, but its anti-inflammatory, antiviral, anti-tumor and other non-anticoagulant biolo-gical activities are still under extensive research, and these activities also have the potential to be developed into new drugs and new materials.Derivatives which with low anticoagulant activity and high antiangiogenic activity have been developed.In addition, sepsis-induced coagulopathy was common in patients with severe pneumonia caused by COVID-19 during the global outbreak of novel coronavirus epidemic.Heparin is effective in improving coagulation disorders and is likely to provide a better prognosis in patients with severe pneumonia.Due to its better biological activity, it also has potential applications in the field of new materials, such as being a cross-linking agent in the formation of hydrogels, and as a surface modifier of nanoparticles. This article consists of five parts, through which the author will first review the pharmacological activities of heparin in anticoagulation, anti-inflammatory and anti-tumor activities, then introduce the application of heparin in the new coronavirus, and finally give an overview of the application of heparin in new materials.

COVID VACCINE-INDUCED RHABDOMYOLYSIS. A CASE OF RECURRENT RHABDOMYOLYSIS

CASE: A 46-year-old African-American female was evaluated for generalized body aches five days after receiving second dose of COVID mRNA-1273 (Moderna) vaccine. Six months prior, she received her first dose of Ad26 (Johnson & Johnson) vaccine without sequelae, Family history includes maternal systemic lupus erythematous. Patient has a history of cystic acne and, most notably, frequent episodes of muscle aches and weakness. In 2006 and 2016, patient was hospitalized for episodes of rhabdomyolysis after receiving influenza vaccine. Autoimmune myositis was ruled out. She has never received statin medication. In late 2017, she was admitted for rhabdomyolysis after upper respiratory tract infection. She reported dark urine but no rash or arthralgia. Patient had elevated CK 107,737 U/L, AST 379 U/L, and ALT 115 U/L. Her renal function, sed rate, TSH, HIV, influenza, direct Coombs, protein electrophoresis, and antinuclear antibodies were negative or within normal limits. She was treated with IV fluids, pain medication, and discharged. In her current admission for rhabdomyolysis, she presented with dark urine, CK 130,702 U/L, AST 692 U/L, ALT 208 U/L, and D-dimer 1,544 ng/mL. No acute renal injury was noted. Patient was treated with intravenous crystalloids and pain medication. CK and transaminases steadily trended down. Patient was discharged as she was asymptomatic and CK had dropped significantly. IMPACT/DISCUSSION: Rhabdomyolysis can be an adverse event to vaccine administration, most commonly influenza vaccination. Detection of SARS-CoV-2 inside skeletal muscle has not been documented. Reports on COVID- 19 vaccine-induced rhabdomyolysis focus on the type of vaccine the patient received, the number of doses that triggered the event, CK level, and presence of risk factors for developing rhabdomyolysis. Although no pathophysiologic mechanism has been established, several hypotheses exist to explain muscle damage including genetic factors, autoimmune reactions to the virus nucleic material, or external adjuvant. This has been described as autoimmune/inflammatory syndrome induced by adjuvants. Our patient had a history of recurrent episodes of rhabdomyolysis after receiving influenza and COVID immunizations, as well as viral infection. CONCLUSION: The mechanism of our patients' reaction is unknown. Reported cases support autoimmunity as the major risk factor for vaccinerelated rhabdomyolysis. This patient had elevated CK level on subsequent episodes of rhabdomyolysis fitting the pattern where a more exaggerated response of the immune system is observed every time patient is re-exposed to known insult. Genetic predisposition may also play a role. AfricanAmericans have higher prevalence of slow acetylation and carnitine palmitoyltransferase II deficiency, a disorder of fatty acid. The myopathic form presents with high CK values. Therefore, patients should be counseled to seek medical attention when symptoms occur and physicians should consider vaccination as a possible cause.

Catching BETs by viruses.

Viruses use diverse tactics to hijack host cellular machineries to evade innate immune responses and maintain their life cycles. Being critical transcriptional regulators, human BET proteins are prominent targets of a growing number of viruses. The BET proteins associate with chromatin through the interaction of their bromodomains with acetylated histones, whereas the carboxy-terminal domains of these proteins contain docking sites for various human co-transcriptional regulators. The same docking sites however can be occupied by viral proteins that exploit the BET proteins to anchor their genome components to chromatin in the infected host cell. In this review we highlight the pathological functions of the BET proteins upon viral infection, focusing on the mechanisms underlying their direct interactions with viral proteins, such as the envelope protein from SARS-CoV-2.

Targeting Histone Deacetylases in Idiopathic Pulmonary Fibrosis: A Future Therapeutic Option.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options, and there is a huge unmet need for new therapies. A growing body of evidence suggests that the histone deacetylase (HDAC) family of transcriptional corepressors has emerged as crucial mediators of IPF pathogenesis. HDACs deacetylate histones and result in chromatin condensation and epigenetic repression of gene transcription. HDACs also catalyse the deacetylation of many non-histone proteins, including transcription factors, thus also leading to changes in the transcriptome and cellular signalling. Increased HDAC expression is associated with cell proliferation, cell growth and anti-apoptosis and is, thus, a salient feature of many cancers. In IPF, induction and abnormal upregulation of Class I and Class II HDAC enzymes in myofibroblast foci, as well as aberrant bronchiolar epithelium, is an eminent observation, whereas type-II alveolar epithelial cells (AECII) of IPF lungs indicate a significant depletion of many HDACs. We thus suggest that the significant imbalance of HDAC activity in IPF lungs, with a "cancer-like" increase in fibroblastic and bronchial cells versus a lack in AECII, promotes and perpetuates fibrosis. This review focuses on the mechanisms by which Class I and Class II HDACs mediate fibrogenesis and on the mechanisms by which various HDAC inhibitors reverse the deregulated epigenetic responses in IPF, supporting HDAC inhibition as promising IPF therapy.

Biological Resistance of Acetylated Radiata Pine, European Beech, and MDF against Marine Borers at Three Italian Sites after Five Years Immersion

The aim of this research was to determine the resistance of acetylated wood against marine biodeterioration in use class 5 for use in temperate waters. The resistance of acetylated radiata pine (Pinus radiata D. Don) on solid and medium-density fiberboard (MDF) panels was compared with untreated wood of European species, such as European beech (Fagus sylvatica L.), sweet chestnut (Castanea sativa Mill.), European oak (Quercus robur L.), and marine plywood. As a reference control, untreated Scots pine (Pinus sylvestris L.) sapwood was used. The field tests were carried out in accordance with EN 275, and started in April 2015. The three Italian exposure sites were Marine of Scarlino private harbor, Port of Genoa, and the Venice Lagoon. Final evaluation in 2021 showed a greater resistance to marine borers of acetylated wood, radiata pine, and beech and MDF panels. However, the untreated European species showed low resistance against marine organisms, with complete decay after the first year of exposure.

(1R,2R,3S,4R)-1-(Acetylamino)-2,4,5-tris(acetyloxy)-1-((2S)-4-(benzyloxy)-5-oxo-2,5-dihydrofuran-2-yl)pentan-3-yl Acetate

Treatment of N-acetylneuraminic acid with excess base in the presence of benzyl bromide gives a polyhydroxylated 1,4 lactone which after acetylation gave the title compound in 20% overall yield. The structure of the product was confirmed by single crystal X-ray diffraction analysis, as well as FT-IR, NMR spectroscopic and HRMS analysis.

Molecular Mechanisms of Vascular Damage During Lung Injury.

A variety of pulmonary and systemic insults promote an inflammatory response causing increased vascular permeability, leading to the development of acute lung injury (ALI), a condition necessitating hospitalization and intensive care, or the more severe acute respiratory distress syndrome (ARDS), a disease with a high mortality rate. Further, COVID-19 pandemic-associated ARDS is now a major cause of mortality worldwide. The pathogenesis of ALI is explained by injury to both the vascular endothelium and the alveolar epithelium. The disruption of the lung endothelial and epithelial barriers occurs in response to both systemic and local production of pro-inflammatory cytokines. Studies that evaluate the association of genetic polymorphisms with disease risk did not yield many potential therapeutic targets to treat and revert lung injury. This failure is probably due in part to the phenotypic complexity of ALI/ARDS, and genetic predisposition may be obscured by the multiple environmental and behavioral risk factors. In the last decade, new research has uncovered novel epigenetic mechanisms that control ALI/ARDS pathogenesis, including histone modifications and DNA methylation. Enzyme inhibitors such as DNMTi and HDACi may offer new alternative strategies to prevent or reverse the vascular damage that occurs during lung injury. This review will focus on the latest findings on the molecular mechanisms of vascular damage in ALI/ARDS, the genetic factors that might contribute to the susceptibility for developing this disease, and the epigenetic changes observed in humans, as well as in experimental models of ALI/ADRS.

In-vitro acetylation of SARS-CoV and SARS-CoV-2 nucleocapsid proteins by human PCAF and GCN5.

Recently, the novel coronavirus (SARS-CoV-2), which has spread from China to the world, was declared a global public health emergency, which causes lethal respiratory infections. Acetylation of several proteins plays essential roles in various biological processes, such as viral infections. We reported that the nucleoproteins of influenza virus and Zaire Ebolavirus were acetylated, suggesting that these modifications contributed to the molecular events involved in viral replication. Similar to influenza virus and Ebolavirus, the coronavirus also contains single-stranded RNA, as its viral genome interacts with the nucleocapsid (N) proteins. In this study, we report that SARS-CoV and SARS-CoV-2 N proteins are strongly acetylated by human histone acetyltransferases, P300/CBP-associated factor (PCAF), and general control nonderepressible 5 (GCN5), but not by CREB-binding protein (CBP) in vitro. Liquid chromatography-mass spectrometry analyses identified 2 and 12 acetyl-lysine residues from SARS-CoV and SARS-CoV-2 N proteins, respectively. Particularly in the SARS-CoV-2 N proteins, the acetyl-lysine residues were localized in or close to several functional sites, such as the RNA interaction domains and the M-protein interacting site. These results suggest that acetylation of SARS-CoV-2 N proteins plays crucial roles in their functions.

Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis.

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins' functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

In silico investigation of the viroporin E as a vaccine target against SARS-CoV-2.

Viroporins, integral viral membrane ion channel proteins, interact with host-cell proteins deregulating physiological processes and activating inflammasomes. Severity of COVID-19 might be associated with hyperinflammation, thus we aimed at the complete immunoinformatic analysis of the SARS-CoV-2 viroporin E, P0DTC4. We also identified the human proteins interacting with P0DTC4 and the enriched molecular functions of the corresponding genes. The complete sequence of P0DTC4 in FASTA format was processed in 10 databases relative to secondary and tertiary protein structure analyses and prediction of optimal vaccine epitopes. Three more databases were accessed for the retrieval and the molecular functional characterization of the P0DTC4 human interactors. The immunoinformatics analysis resulted in the identification of 4 discontinuous B-cell epitopes along with 1 linear B-cell epitope and 11 T-cell epitopes which were found to be antigenic, immunogenic, nonallergen, nontoxin, and unable to induce autoimmunity thus fulfilling prerequisites for vaccine design. The functional enrichment analysis showed that the predicted host interactors of P0DTC4 target the cellular acetylation network. Two of the identified host-cell proteins - BRD2 and BRD4 - have been shown to be promising targets for antiviral therapy. Thus, our findings have implications for COVID-19 therapy and indicate that viroporin E could serve as a promising vaccine target against SARS-CoV-2. Validation experiments are required to complement these in silico results.

The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections.

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.

SARS-CoV-2 Evolutionary Adaptation toward Host Entry and Recognition of Receptor O-Acetyl Sialylation in Virus-Host Interaction.

The recently emerged SARS-CoV-2 is the cause of the global health crisis of the coronavirus disease 2019 (COVID-19) pandemic. No evidence is yet available for CoV infection into hosts upon zoonotic disease outbreak, although the CoV epidemy resembles influenza viruses, which use sialic acid (SA). Currently, information on SARS-CoV-2 and its receptors is limited. O-acetylated SAs interact with the lectin-like spike glycoprotein of SARS CoV-2 for the initial attachment of viruses to enter into the host cells. SARS-CoV-2 hemagglutinin-esterase (HE) acts as the classical glycan-binding lectin and receptor-degrading enzyme. Most ß-CoVs recognize 9-O-acetyl-SAs but switched to recognizing the 4-O-acetyl-SA form during evolution of CoVs. Type I HE is specific for the 9-O-Ac-SAs and type II HE is specific for 4-O-Ac-SAs. The SA-binding shift proceeds through quasi-synchronous adaptations of the SA-recognition sites of the lectin and esterase domains. The molecular switching of HE acquisition of 4-O-acetyl binding from 9-O-acetyl SA binding is caused by protein-carbohydrate interaction (PCI) or lectin-carbohydrate interaction (LCI). The HE gene was transmitted to a ß-CoV lineage A progenitor by horizontal gene transfer from a 9-O-Ac-SA-specific HEF, as in influenza virus C/D. HE acquisition, and expansion takes place by cross-species transmission over HE evolution. This reflects viral evolutionary adaptation to host SA-containing glycans. Therefore, CoV HE receptor switching precedes virus evolution driven by the SA-glycan diversity of the hosts. The PCI or LCI stereochemistry potentiates the SA-ligand switch by a simple conformational shift of the lectin and esterase domains. Therefore, examination of new emerging viruses can lead to better understanding of virus evolution toward transitional host tropism. A clear example of HE gene transfer is found in the BCoV HE, which prefers 7,9-di-O-Ac-SAs, which is also known to be a target of the bovine torovirus HE. A more exciting case of such a switching event occurs in the murine CoVs, with the example of the ß-CoV lineage A type binding with two different subtypes of the typical 9-O-Ac-SA (type I) and the exclusive 4-O-Ac-SA (type II) attachment factors. The protein structure data for type II HE also imply the virus switching to binding 4-O acetyl SA from 9-O acetyl SA. Principles of the protein-glycan interaction and PCI stereochemistry potentiate the SA-ligand switch via simple conformational shifts of the lectin and esterase domains. Thus, our understanding of natural adaptation can be specified to how carbohydrate/glycan-recognizing proteins/molecules contribute to virus evolution toward host tropism. Under the current circumstances where reliable antiviral therapeutics or vaccination tools are lacking, several trials are underway to examine viral agents. As expected, structural and non-structural proteins of SARS-CoV-2 are currently being targeted for viral therapeutic designation and development. However, the modern global society needs SARS-CoV-2 preventive and therapeutic drugs for infected patients. In this review, the structure and sialobiology of SARS-CoV-2 are discussed in order to encourage and activate public research on glycan-specific interaction-based drug creation in the near future.