Coronaviruses are single-stranded RNA viruses that are common in animals. In the past 20 years, there have been three large-scale epidemics of coronaviruses, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease (COVID). Heart disease is an independent risk factor for severe COVID. At the same time, SARS-CoV-2 infection is often complicated with myocardial injury, which is closely related to poor prognosis. The receptors of SARS coronavirus are angiotensin-converting enzyme 2 (ACE2) and CD209L, among which ACE2 is the main receptor, and ACE2 is abundant in the heart. The receptor of MERS-coronavirus is dipeptide peptidase 4 (DPP4), which is not expressed in myocardial cells, but existed in vascular endothelial cells and blood. These receptors are important factors for the myocardial injury caused by coronavirus infection.
Animals ; COVID-19 ; Angiotensin-Converting Enzyme 2 ; SARS-CoV-2 ; Endothelial Cells ; Peptidyl-Dipeptidase A/genetics*

Background: Hypertension is a worldwide epidemic that has been recognized as the most leading global risk for mortality, with its prevalence associated with increased blood pressure, concomitant risks of cardiovascular and kidney diseases, and major commonality in individuals advanced in age. With the current treatment options for hypertension management, there is still a need to develop therapies that directly target receptors that aid in hypertension treatment. Methodology: The study focused on the in-silico profiling of the reported compounds from Areca catechu L. (fam. Arecaceae) towards the n-domain and c-domain angiotensin converting enzyme (ACE) receptor models. Bioisosteric replacement was used to create bioisosteres investigated for similar binding affinity. Results: Some A. catechu compounds exhibited favorable binding energies towards the n- and c-domain receptor models of ACE, binding in the same ACE ligand binding site as lisinopril, benazepril, and sampatrilat via similar interactions and amino acid residues. The majority of A. catechu compounds with favorable ACE binding energies belong to the phytochemical classes of flavonoids, polyphenols and phenolics, glycosides, and steroids. After in silico toxicity and pharmacokinetic profiling, the bioisosteres Leuco-DM02-39, Leuco-DM02-66, Leuco-DM05-60, Querc-DM09-63, and Querc-DM14-31 with binding energies higher than their parent compounds and comparable to lisinopril, benazepril, and sampatrilat were deemed the best. Conclusion A. catechu compounds have the potential to target ACE n-domain and c-domain receptor models. Three leucocyanidin and two quercetin bioisosteres exhibited favorable binding to the n-domain and c-domain ACE receptor models and could be further optimized to derive a promising antihypertensive agent through ACE inhibition.
Peptidyl-Dipeptidase A ; Areca ; Hypertension

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected 660 million people and resulted in 6.7 million deaths. At present, a variety of risk factors related to the severity of COVID-19 have been identified, but whether allergic rhinitis and asthma will affect SARS-CoV-2 infection remains controversial. In general, there is no sufficient evidence to support that allergic rhinitis or asthma is a risk factor for increasing the rate of SARS-CoV-2 infection or aggravating the disease. Some studies even show that atopy may be a protective factor to alleviate SARS-CoV-2 infection, which is related to the decreased expression of angiotensin-converting enzyme 2, the receptor required for SARS-CoV-2 to enter cells, in atopic individuals. This paper reviews the influence of the severity and treatment of allergic rhinitis and asthma on SARS-CoV-2 infection, in order to provide some references for establishing strategies for prevention, risk stratification and treatment of COVID-19.
Humans ; COVID-19 ; SARS-CoV-2/metabolism* ; Peptidyl-Dipeptidase A/metabolism* ; Asthma/therapy* ; Rhinitis, Allergic

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected 660 million people and resulted in 6.7 million deaths. At present, a variety of risk factors related to the severity of COVID-19 have been identified, but whether allergic rhinitis and asthma will affect SARS-CoV-2 infection remains controversial. In general, there is no sufficient evidence to support that allergic rhinitis or asthma is a risk factor for increasing the rate of SARS-CoV-2 infection or aggravating the disease. Some studies even show that atopy may be a protective factor to alleviate SARS-CoV-2 infection, which is related to the decreased expression of angiotensin-converting enzyme 2, the receptor required for SARS-CoV-2 to enter cells, in atopic individuals. This paper reviews the influence of the severity and treatment of allergic rhinitis and asthma on SARS-CoV-2 infection, in order to provide some references for establishing strategies for prevention, risk stratification and treatment of COVID-19.
Humans ; COVID-19 ; SARS-CoV-2/metabolism* ; Peptidyl-Dipeptidase A/metabolism* ; Asthma/therapy* ; Rhinitis, Allergic

Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with strong contagiousness, high susceptibility and long incubation period. cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain of the viral spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). Here, we briefly reviewed the mechanisms underlying the interaction between SARS-CoV-2 and ACE2, and summarized the latest research progress on SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies, so as to better understand the development process and drug research direction of COVID-19. This review may facilitate understanding the development of neutralizing antibody drugs for emerging infectious diseases, especially for COVID-19.
Angiotensin-Converting Enzyme 2 ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Humans ; Peptidyl-Dipeptidase A/metabolism* ; Protein Binding ; SARS-CoV-2 ; Single-Domain Antibodies ; Spike Glycoprotein, Coronavirus/metabolism*

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.
Adult ; Animals ; COVID-19 ; Epithelial Cells ; Humans ; Lung ; Mice ; Pandemics ; Peptidyl-Dipeptidase A ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Ubiquitin-Protein Ligases/genetics*

OBJECTIVE: To provide data support for the study of pathogenic mechanism of SARS-CoV-2 at the molecular level, and provide suitable candidate targets for vaccine, antibody and drug research and development through comparative analysis for structural characteristics and epitopes of S protein of SARS-CoV-2 and SARS-CoV. METHODS: Based on the reference sequences of S protein, physical and chemical properties, hydrophobicity, signal peptide, transmembrane region, domain, secondary structure, tertiary structure analysis and antigenic epitopes prediction were carried out. Meanwhile, the tissue expression, related pathways and reactome pathways of angiotensis Ⅰ converting enzyme 2 (ACE2) and C-type lectin domain family 4 member M (CLEC4M) receptors were analyzed. RESULTS: The amino acid sequence of S protein of SARS-CoV-2 and SARS-CoV has a 75.80% consistency. The structural characteristics of the two coronaviruses are highly consistent, but the secondary structure and tertiary structure of SARS-CoV-2 is not as obvious as SARS-CoV. ACE2 and CLEC4M are expressed in alimentary system, heart, kidney, lung and placenta. The main related the pathways of renin-angiotensin system, protein digestion and absorption pathway, and the reactome pathways of metabolism of angiotensinogen to angiotensins, GPCR ligand binding, are related to typical symptoms of coronavirus disease 2019 induced by SARS-CoV-2. Three pairs of highly or completely homologous epitopes of S protein were obtained. The 600-605, 695-703 and 888-896 amino acid residues in SARS-CoV-2 were highly homologous with 586-591, 677-685 and 870-878 amino acid residues in SARS-CoV, respectively. CONCLUSIONS The similarity of S protein of SARS-CoV-2 and SARS-CoV determines that they have similar infection patterns and clinical manifestations. The candidate epitopes with high reliability can provide reference for virus diagnosis and vaccine development.
Betacoronavirus ; Cell Adhesion Molecules ; Coronavirus Infections ; Epitopes ; Humans ; Lectins, C-Type ; Ligands ; Pandemics ; Peptidyl-Dipeptidase A ; Pneumonia, Viral ; Receptors, Cell Surface ; Receptors, Virus ; Reproducibility of Results ; Spike Glycoprotein, Coronavirus

2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.
Betacoronavirus ; isolation & purification ; pathogenicity ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; transmission ; Humans ; Mouth ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; metabolism ; Pharynx ; virology ; Pneumonia, Viral ; diagnosis ; transmission ; SARS Virus ; isolation & purification ; pathogenicity ; Saliva ; virology

Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load

Angiotensin I ; physiology ; Betacoronavirus ; pathogenicity ; physiology ; Coronavirus Infections ; virology ; Humans ; Pandemics ; Peptide Fragments ; physiology ; Peptidyl-Dipeptidase A ; physiology ; Pneumonia, Viral ; virology