Clinical Effect of Yinhuang Qingfei Capsules in Treatment of Asymptomatic and Mild/Common Severe Acute Respiratory Syndrome Coronavirus 2 Infection:An Analysis of 242 Cases

[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.

Huu S. TIEU’s Predicting Outcome of Severe Acute Respiratory Syndrome (SARS) and Preparing the Treatment for COVID-19 (Coronavirus) and Other Viral Pandemics

This project paper is to give a prediction for the future of other viral pandemics and to provide recommendations for preparing therapies that could help in the success of effective treatments and benefits for patients in life-threatening situations. The theory of prediction was proposed by Huu S. TIEU on March 25, 2019, and he hypothesized that any malfunctioning cell in the body could have a damaging effect. This paper discusses the prediction that Localized Oxygen Deprivation could be a contributing factor for a future epidemic or other viral pandemics that could affect body function. This paper is based on opinion and does not have sufficient evidence to support the claims made. Therefore, further in-depth study is needed to prove the findings. The author cites Hypoxia to support his idea, but he is not claiming that Hypoxia-Inducible Factor (HIF) has worked on his predictions. The author also tested a theory using cow blood curd for body function, but this test was not a structured test and the findings were not supported by other evidence. To further prove the idea or theory, further study into the subject should be conducted.

Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na^(+)/H^(+) exchanger

The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.

Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic

The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions.

Biology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the humoral immunoresponse:a systematic review of evidence to support global policy-level actions and research

Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.

The role of immunoinformatics in analysis of immune response against severe acute respiratory syndrome (SARS) coronavirus

In order to analyze the immune response to severe acute respiratory syndrome （SARS） coronavirus （SARS-CoV）, immunoinformatics and computational analyses were performed to study the immunological characters of SARS-CoV. According to the results of immunoinformatics analysis, the obvious variation of HLA-A2 associated T cell epitopes between SARS vires and HCoV-229E was found as follows： （1） Disappearance of HIA-A2 binding site; （2） variation sequence on the HLA-A2 associated epitope; （3） emergence of a new HLA-A2 associated epitope. The immunoinfomatics results were evidenced by T2 cell binding assay, ELISPOT and DimerX staining. In conclusion, immunoinformatics is a useful method to analyze the immunological character of a new finding infectious pathogen, like SARS-CoV. These findings of immunoinformatics are confirmed by lab and clinical experiments. In this case, immunoinformatics seems a very useful tool in the study of immune response and the evaluation of vaccine in infectious diseases, such as SARS.

Epidemiological Characteristics of An Outbreak of Severe Acute Respiratory Syndrome in Dongcheng District of Beijing From March to May 2003

Objective To describe epidemiologic features of an outbreak of severe acute respiratory syndrome (SARS) in Dongcheng District, Beijing occurred in a period between March and May 2003. Methods Data of SARS cases notified from Dongcheng District Center for Disease Control and Prevention (CDC )and supplemented by other channels were collected. Clinicians and officials of local hospitals were interviewed in groups and medical records of fatal cases of SARS were reviewed to verify the diagnosis. Stored serum specimens of the patients were detected for IgG antibody against SARS Co-V by enzyme-linked immunosorbent assay (ELISA). All the data were input into dataset files by Microsoft Excel-2000 software and analyzed with SPSS version 10.0 software. Results Outbreak of SARS in Dongcheng District started on March 14, 2003 with a peak in mid- and late April, and dropped in early May. A total of 572 reported cases were collected during this period in Dongcheng District, Beijing, and 99 of them were excluded from SARS, because of diagnosis of common cold, regular pneumonia, measles and rubella, etc. Actually, 473 SARS cases, which included 390 (82.5%) probable cases and 83 (17.5%) suspect cases, were analyzed. About 90% of the probable cases were positive for IgG antibody. Attack rate of SARS in permanent residents of Dongcheng District was 28.3 per 100 000. Forty-one of them died, with a case-fatality rate of 8.7%. Persons were all susceptible to infection of SARS Co-V, with the highest proportion at ages of 20-50 years, which accounted for 68.7% of the total cases. Average age of the patients at their onset was 40.7 years. No gender difference in SARS cases was found. Number of SARS cases in health-care workers (HCWs) accounted for 18.0% and that in retired workers accounted for 15.4% of the total cases. Cases occurred in all 10 sub-districts of Dongcheng, with the highest in Beixinqiao and Andingmen Sub-districts. Totally, 230 of the 572 notified cases (40.2%) were hospitalized at local hospitals under the jurisdiction of Dongcheng District. Eighteen of 85 cases of SARS occurred in HCWs of local hospitals, accounting for 4.5% of the total number of HCWs working at wards caring for SARS patients or fever clinics. There were 34.7% of SARS cases without any histories of contact before the onset of the disease. Familial aggregation phenomena were observed in 41.8% of the cases and 18.1% of households. And 7.4% (attack rate ) of those exposed to SARS cases suffered from the illness during the periods of quarantine. Conclusions SARS appeared to be infectious in origin and caused outbreak in Dongcheng District, Beijing introduced by an imported case traveling from Hong Kong in a period between March and May 2003. People are all susceptible to infection of SARS Co-V, which mainly threatens the young adults and the middle-aged, as well as HCWs and the retired workers. The main mode of transmission is direct exposure to SARS patients in a near distance at hospitals or families via droplets spread. Prevention and control of SARS should be focused on early isolation of patients and quarantine for close contacts. Current available measures to prevent and control SARS are proved to be effective.

Elevated Plasma Tissue-type Plasminogen Activator (t-PA) and Soluble Throm-bomodulin in Patients Suffering From Severe Acute Respiratory Syndrome (SARS) as a Possible Index for Prognosis and Treatment Strategy

To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection as A Risk Factor for Thromboembolic and Acute Ischemic Stroke:A Case Report

Increasing evidence reports a greater incidence of stroke in patients with coronavirus disease 2019(COVID-19)than in the non-COVID-19 population and suggests that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection represents a risk factor for thromboembolic and acute ischemic stroke.Elderly people have higher risk factors for acute ischemic stroke or embolic vascular events,and advanced age is strongly associated with severe COVID-19 and death.We reported,instead,a case of an ischemic stroke in a young woman during her hospitalization for COVID-19-related pneumonia.A 29-year-old woman presented to the emergency department of the First Affiliated Hospital,Zhejiang University School of Medicine with progressive respiratory distress associated with a 2-day history of fever,nausea,and vomiting.The patient was transferred to the intensive care unit(ICU),where she underwent tracheostomy for mechanical ventilation due to her severe clinical condition and very low arterial partial pressure of oxygen.The nasopharyngeal swab test confirmed SARS-CoV-2 infection.Laboratory tests revealed neutrophilic leukocytosis,prolonged prothrombin time,and elevated D-dimer and fibrinogen levels.Left hemiplegia was reported 18 days later during her stay in the ICU after discontinuation of the sedative medications.Central facial palsy on the left side,dysarthria,and facial droop were present,with complete paralysis of the ipsilateral upper and lower limbs.Computed tomography(CT)of the head and magnetic resonance imaging of the brain confirmed the presence of lesions in the right hemisphere affecting the territories of the anterior and middle cerebral arteries,consistent with ischemic stroke.Pulmonary and splenic infarcts were also found after CT of the chest.The age of the patient and the absence of serious concomitant cardiovascular diseases place the emphasis on the capacity of SARS-CoV-2 infection to be an independent cerebrovascular risk factor.Increased levels of D-dimer and positivity forβ2-glycoprotein antibody could confirm the theory of endothelial activation and hypercoagulability,but other mechanisms-still under discussion-should not be excluded.

Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection:Bioinformatics and molecular simulation analyses

Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

Comparison of acute pneumonia caused by SARS-CoV-2 and other respiratory viruses in children:a retrospective multi-center cohort study during COVID-19 outbreak

Background:Until January 18,2021,coronavirus disease-2019(COVID-19)has infected more than 93 million individuals and has caused a certain degree of panic.Viral pneumonia caused by common viruses such as respiratory syncytial virus,rhinovirus,human metapneumovirus,human bocavirus,and parainfluenza viruses have been more common in children.However,the incidence of COVID-19 in children was significantly lower than that in adults.The purpose of this study was to describe the clinical manifestations,treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak.Methods:Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study.A total of 64 children with COVID-19 were defined as the COVID-19 cohort,of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort.Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort.The epidemiologic,clinical,and laboratory findings were compared by Kolmogorov-Smirnov test,t-test,Mann-Whitney U test and Contingency table method.Drug usage,immunotherapy,blood transfusion,and need for oxygen support were collected as the treatment indexes.Mortality,intensive care needs and symptomatic duration were collected as the outcome indicators.Results:Compared with the viral pneumonia cohort,children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19(53/64 vs.23/284),were of older median age(6.3 years vs.3.2 years),and had a higher proportion of ground-glass opacity(GGO)on computed tomography(18/40 vs.0/38,P<0.001).Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases(1/40 vs.38/284,P=0.048),and lower cases with high fever(3/40 vs.167/284,P<0.001),requiring intensive care(1/40 vs.32/284,P<0.047)and with shorter symptomatic duration(median 5d vs.8d,P<0.001).The proportion of cases with evaluated inflammatory indicators,biochemical indicators related to organ or tissue damage,D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort(P<0.05).No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs(lopinavir-ritonavir,ribavirin,and arbidol)as compared with duration in 39 children without antiviral therapy(median 10d vs.9d,P=0.885).Conclusions:The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia.Lopinavir-ritonavir,ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19.During the COVID-19 outbreak,attention also must be given to children with infection by other pathogens infection.

Antiviral activity of cepharanthine against severe acute respiratory syndrome coronavirus in vitro

Severe acute respiratory syndrome(SARS) is the first severe viral epidemic we encountered his century,which once spread in more than thirty countriesin2003.1 The etiological agent of SARS has beenc onfirmed to be a novel coronavirus,namely SARS coronavirus(SARS-CoV),2,3 and the first outbreak of SARS has been successfully controlled world wide,but the identification of SARS-CoV isolated from wildanimals,the emergence of some sporadic SARS cases laterafter that outbreak,all suggest that the recurrence of such an epidemic is not unlikely in the future.In this case,development of SARS vaccines and specific drugs is undoubtedlyessential to the control and prevention from the possible outbreak.4,5

The protein X4 of severe acute respiratory syndrome-associated coronavirus is expressed on both virus-infected cells and lung tissue of severe acute respiratory syndrome patients and inhibits growth of Balb/c 3T3 cell line

Background The genome of the severe acute respiratory syndrome-associated coronavirus ( SARS-CoV) includes sequences encoding the putative protein X4 ( ORF8, ORF7a), consisting of 122 amino acids. The deduced sequence contains a probable cleaved signal peptide sequence and a C-terminal transmembrane helix, indicating that protein X4 is likely to be a type I membrane protein. This study was conducted to demonstrate whether the protein X4 was expressed and its essential function in the process of SARS-CoV infection. Methods The prokaryotic and eukaryotic protein X4-expressing plasmids were constructed. Recombinant soluble protein X4 was purified from E. coli using ion exchange chromatography, and the preparation was injected into chicken for rising specific polyclonal antibodies. The expression of protein X4 in SARS-CoV infected Vero E6 cells and lung tissues from patients with SARS was performed using immunofluorescence assay and immunohistochemistry technique. The preliminary function of protein X4 was evaluated by treatment with and over-expression of protein X4 in cell lines. Western blot was employed to evaluate the expression of protein X4 in SARS-CoV particles. Results We expressed and purified soluble recombinant protein X4 from E. coli, and generated specific antibodies against protein X4. Western blot proved that the protein X4 was not assembled in the SARS-CoV particles. Indirect immunofluorescence assays revealed that the expression of protein X4 was detected at 8 hours after infection in SARS-CoV-infected Vero E6 cells. It was also detected in the tung tissues from patients with SARS. Treatment with and overexpression of protein X4 inhibited the growth of Balb/c 313 cells as determined by cell counting and MTT assays. Conclusion The results provide the evidence of protein X4 expression following SARS-CoV infection, and may facilitate further investigation of the immunopathological mechanism of SARS.

Severe acute respiratory syndrome-associated coronavirus genotype and its characterization

Objective To study the severe acute respiratory syndrome (SARS) -associated coronavirus genotype and its characteristics.Methods A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29 715 bp (GenBank accession: AY297028, version; gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done.Results By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C: G: C: C/T: T: T: T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C: G: A: C: C/T: T: G: T: T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in China's Mainland. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to He in the protein, respectively.Conclusion Attention should be paid to whether these genotype and mutation patterns are related to the virus' s biological activities, epidemic characteristics and host clinical symptoms.

Immune response in Balb/c mice induced by recombinant spike protein of severe acute respiratory syndrome coronavirus

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly aggressive pathogen that caused SARS in 2003 and 2004.^(1-4) Spike protein (S) on the surface of virus particles mediates the attachment of the virus to cell surface receptors and induces the fusion of viral and cellular membranes. According to the epitope analysis and structure of S protein, we used two fragments of S protein S1 (108-488aa) and S2 (723-938aa) expressed in Escherichia coli and immunized Balb/c mice to investigate the immune response to the recombinant proteins in mice.~5

Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc(and STAT) interactor

Severe acute respiratory syndrome coronavirus(SARS-Co V) encodes eight accessory proteins, the functions of which are not yet fully understood. SARS-Co V protein 6(P6) is one of the previously studied accessory proteins that have been documented to enhance viral replication and suppress host interferon(IFN) signaling pathways. Through yeast two-hybrid screening, we identified eight potential cellular P6-interacting proteins from a human spleen c DNA library. For further investigation, we targeted the IFN signaling pathway-mediating protein, N-Myc(and STAT) interactor(Nmi). Its interaction with P6 was confirmed within cells. The results showed that P6 can promote the ubiquitin-dependent proteosomal degradation of Nmi. This study revealed a new mechanism of SARS-Co V P6 in limiting the IFN signaling to promote SARS-Co V survival in host cells.

Molecular biological analysis of genotyping and phylogeny of severe acute respiratory syndrome associated coronavirus

Background SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong,Hong Kong and Beijing of China,and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper. Methods Full or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype,single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological,bioinformatic and epidemiological methods. Results There were 188 point mutations in the 33 virus full genomes with the counts of mutation mounting to 297. Further analysis was carried out among 36 of 188 loci with more than two times of mutation. All the 36 mutation loci occurred in coding sequences and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB,S2 domain of spike glycoprotein and nucleocapsid protein were lower (0.079%-0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this small domain (120 bp) and 3 of 4 loci related to deletion mutation. By bioinformatics processing and analysis,the nucleotides at 7 loci of genome (T∶T∶A∶G∶T∶C∶T/C∶G∶G∶A∶C∶T∶C) can classify SARS-CoV into two types. Therefore a novel definition is put forward that according to these 7 loci of mutation,40 strains of SARS-CoV in GenBank can be grouped into two genotypes,T∶T∶A∶G∶T∶C∶T and C∶G∶ G∶A∶ C∶T∶C,and named as SARS-CoV Yexin genotype and Xiaohong genotype. The two genotypes can be further divided into some sub-genotypes. These genotypes can also be approved by phylogenetic tree of three levels of 44 loci of mutation, spike glycoprotein gene and complete genome sequence. Compared to various strains among SARS-CoV Yexin genotype and Xiaohong genotype,GD01 strain of Yexin genotype is more closely related to SARS-CoV like-virus from animals. Conclusion The results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues,information and evidence of molecular biology for the clinical pathology,vaccine developing and epidemic investigation.

Comprehensive Comparison and Analysis of the Prevention and Treatment of Coronavirus Disease 2019 and Severe Acute Respiratory Syndrome with Traditional Chinese Medicine

Since December 2019 the Coronavirus Disease 2019(COVID-19)has erupted in many places around the world,which is strong infectious and highly epidemic.After the outbreak of COVID-19 in China,traditional Chinese medicine(TCM)has been in the front line of the fight against the epidemic.It has shown characteristics and advantages in the prevention and treatment of COVID-19.TCM also played an important role in the winter of 2002 and in the spring of 2003 during the outbreak of severe acute respiratory syndrome(SARS).This article compares the strategies,programs,measures,resource investments,and effects of TCM for the prevention and treatment of COVID-19 with those for SARS.At present,the involvement of TCM has been earlier,faster,and more comprehensive in the fight against the epidemic and has shown good clinical efficacy and treatment prospects.

Cold chain and severe acute respiratory syndrome coronavirus 2 transmission:a review for challenges and coping strategies

Since June 2020,the re-emergence of coronavirus disease 2019(COVID-19)epidemics in parts of China was linked to the cold chain,which attracted extensive attention and heated discussions from the public.According to the typical characteristics of these epidemics,we speculated a possible route of transmission from cold chain to human.A series of factors in the supply chain contributed to the epidemics if the cold chain were contaminated by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),such as temperature,humidity,personal hygiene/protection,and disinfection.The workers who worked in the cold chain at the receiving end faced a higher risk of being infected when they were not well protected.Facing the difficult situation,China put forward targeted and powerful countermeasures to block the cold chain-related risk.However,in the context of the unstable pandemic situation globally,the risk of the cold chain needs to be recognized and evaluated seriously.Hence,in this review,we reviewed the cold chain-related epidemics in China,analyzed the possible mechanisms,introduced the Chinese experience,and suggested coping strategies for the global epidemic prevention and control.

Analysis of Similarities and Differences between Coronavirus Disease 2019 and Severe Acute Respiratory Syndrome

Both coronavirus disease 2019(COVID-19)and severe acute respiratory syndrome(SARS)are epidemic,contagious,sudden,and publicly harmful diseases.The whole-genome nucleotide identity of the pathogens causing the two diseases reached 79.5%.The mechanism and treatment of COVID-19 are still under investigation.Combining the experiences of SARS prevention and treatment in 2003,and the case data and literature of COVID-19,the similarities and differences between the two diseases in terms of causes,susceptible people,characteristics,dialectical mode,and treatment were analyzed.The two diseases are both plagues in terms of Chinese medicine.The cause of SARS was"heat poison,"and its pathogenesis was"heat poison,stasis,and qi and yin deficiency."Therefore the treatment regimen was mainly to clear away heat,detoxicate,and expel evil.While the cause of COVID-19 was"wet poison,"and its pathogenesis was"wet,poison,heat,stasis,close,syncope,and yang collapse."Hence the basic treatment strategy was to declare lung and remove dampness.Treatment of COVID-19 was clearing away evil qi as soon as possible,with the basic treatment regimen,which was declaring lung,removing dampness,and dispelling the evil.Combined with Traditional Chinese medicine’s(TCM’s)understanding and experience in SARS prevention and treatment,and Chinese clinical cured cases,we try to provide strategies for people all over the world to understand and respond to COVID-19,through the analysis and comparison.To improve COVID-19 prevention and treatment regimen and give full play to the advantages of TCM.