The outbreak of COVID-2019 has attracted the attention of the international community. This comprehensive review summarizes the research progress of the diagnosis, prevention and treatment of coronaviruses including SARS-CoV and MERS-CoV, which were extracted and compiled from the Cortellis report DISEASE BRIEFING: CORONAVIRUSES (published on January 30th, 2020), in order to provide reference for the scientific research of current epidemic situation.
In late 2019, a novel coronavirus caused febrile respiratory illness(COVID-19) in Wuhan. The continuous spread of COVID-19 in China and its surrounding countries puts forward a new demand for the prevention and control of this epidemic globally. A bibliometric analysis of the research on coronaviruses has been done in this research, and information related to the main countries, core institutions, key research fields were analyzed, which reveals the current research trends of the diagnosis, prevention and treatment of coronaviruses from a global perspective. The results will provide reference for the current joint research.
In December 2019, Wuhan, Hubei Province, an outbreak of pneumonia caused by a novel coronavirus (COVID-19) subsequently spread to all provinces and areas in China and many countries, that was declared as a Public Health Emergency of International Concern (PHEIC) by WHO. It is important to understand and characterize the virus timely to fight with the epidemic. The papers on COVID-19 by the researchers from various fields around the world within two months after the outbreak were studied and found that these studies mainly focused on traceability analysis, detection methods, patient treatment, clinical manifestations, drug development, pathogenic mechanisms, transmission ways, epidemic characteristics. The coronavirus is closely related to bat coronavirus and pangolin coronavirus. It has the same human receptor ACE2 as SARS-CoV, and the infection pathway is confirmed to be the respiratory and digestive systems. The virus indicates person-to-person and asymptomatic transmission. Most of the confirmed cases of COVID-19 are related to Wuhan, and most cases are mild, the elderly have a higher mortality rate. Rapid and sensitive nucleic acid testing is usually used as a basis for diagnosis. Currently, valuable drug candidates such as remdesivir have been screened for clinical trials. Intervention measures such as travel bans and quarantine adopted have effectively reduced the spread of the epidemic.
Since the outbreak of Corona Virus Disease 2019, the speed of diagnosis has been accelerated with the increase of virus detection. This is of great significance for the early treatment and isolation of coronavirus pneumonia patients and the control of the spread of the epidemic. In this paper, based on the patent information for quantitative data analysis, combined with qualitative research, objective display of coronavirus diagnosis technology research and development status. Through the patent application trend, protection market, important patentees, important patents and other dimensions, this paper shows the patent protection profile of coronavirus diagnosis technology, and predicts the future development direction, in order to support the innovation and research of coronavirus diagnosis technology in China.
Coronavirus is a kind of RNA virus which can infect human and animals. Coronavirus can cause severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The coronavirus (SARS-CoV-2) is a new strain which has never been found in human body before. The rapid transmission of SARS-CoV-2 has aroused the attention of governments all over the world and actively sought for vaccines. This report based on the panoramic patent in the field of coronavirus vaccine, comprehensively analyzed the development trend of patents, the output of major countries and institutions. At the same time, the report focuses on revealing the development and distribution of human related vaccines, as well as the research and development status of human related vaccine products. The report aims to provide references and implications for scientific researchers and decision makers in the field of Coronavirus Vaccine.
Antibodies play an important role in the diagnosis, treatment and prevention of diseases. With the continuous spread of pneumonia caused by the infection of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2), it is urgent to research antibodies against the virus. The patent information was downloaded from the IncoPat database and the drug information was downloaded from the Cortellis database. Through the combination of quantitative analysis and qualitative research, the patent situation analysis in the field of human coronavirus could be obtained from various dimensions, including application trends, technology distribution, country or region distribution, organization distribution and market status. The results showed that the United States was the country with the largest amount of patent technology, and China was the main country of patent protection. Three Chinese organizations, including the Chinese Academy of Sciences, entered the list of the global top ten organizations. The research on human coronavirus antibody products was mainly focused on SARS and MERS. In addition, some MERS antibodies entered the clinical stage. The results provide data reference and decision support for the research and development of Corona Virus Disease 2019(COVID-19).
Interferon has broad-spectrum antiviral, immunomodulatory and antitumor effects. Recombinant human interferon α1b is the first class I genetic engineering new drug with independent intellectual property rights in China. After years of research, a variety of dosage forms such as recombinant human interferon α1b injections and sprays for children and adults have been developed. A series of pharmacological, toxicological, pharmacokinetic and clinical studies on interferon α1b for the treatment of pneumonia such as coronavirus have been completed, becoming clinical consensus and guidance documents. According to these results, interferon α aerosol inhalation was recommended as the first anti-viral treatment of novel coronavirus caused pneumonia in multi-version of "National diagnosis and treatment of novel coronavirus caused pneumonia" released by National Health Commission of the People's Republic of China, and achieved good medical effects. Recombinant human interferon α1b spray, as a drug that can prevent viral infections, is widely used in the biological protection of high-exposure populations such as medical personnel, which plays an important role in the prevention and control of the epidemic, and will make contributions to national health and biosafety.
The pneumonia epidemic caused by the new coronavirus (SARS-CoV-2) seriously threatens the health and life of the general public, and has a major impact on China’s economic development and social stability. Because the new coronavirus is highly contagious, spreads fast, and has a high lethality rate, there are no effective vaccines and drugs to prevent and treat it. A small number of patients have developed severe and critical illness or even died. How to accurately resist and block the progression of new coronary pneumonia, and improve the prognosis of patients is the current research hotspot in the medical and health field. This article reviews the recent advances in the latest treatments for pneumonia in severe and critically new coronavirus infections.
Objective: To investigate the effect of S100A9 in proliferation and migration in Fusobacterium nucleatum (Fn)- induced colon cancer HCT116 and SW480 cells. Method:CCK8 assay and Transwell assays were used to detect the proliferation and migration of colon cancer HCT116 and SW480 cells infected with Fn. Real time PCR and Western blot were used to detect expression of S100A9 mRNA and protein in HCT116 and SW480 cells infected with Fn, respectively.After transfecting S100A9 siRNA into cells for silencing S100A9 expression, CCK8 assay and Transwell assays were used to detect the changes of proliferation and migration of HCT116 and SW480 cells infected with Fn. After pre-treatment with NF-κB inhibitor BAY 11-7082, Real time PCR and Western blot were used to detect the changes of S100A9 mRNA and protein in HCT116 and SW480 cells infected with Fn. Result:(1)Fn promotes the proliferation and migration of HCT116 and SW480 cells(P<0.001).(2) The levels of S100A9 mRNA and protein in Fn-infected HCT116 and SW480 cells were significantly higher than that in the control group(P<0.01 or P<0.001), suggesting that S100A9 expression is up-regulated by Fn. (3)The proliferation and migration of Fn- infected HCT116 and SW480 cells were e rescued after silencing S100A9 expression(P<0.001),indicating that S100A9 is involved in it. (4)NF-κB inhibitor effectively inhibited the increase of S100A9 expression induced by Fn. Conclusion: Fn can regulate S100A9 expression by affecting NF-κB activation, and S100A9 is involved in Fn-mediated proliferation and migration of colon cancer cells.
Objective: The regulation effect of G-quadruplexes (G4) on the SUMO-specific proteases 1 (SENP1) transcriptional expression was studied. Method: Reporting plasmids of SENP1 promoter were constructed by cloning different SENP1 promoter fragments. The core transcriptional regulatory region of SENP1 promoter was identified by using reporter assay. The sequence of core transcriptional regulatory region of SENP1 promoter was analyzed and G-quadruplex (G4) formation sequence was predicted. Oligonucleotides of G4 formation sequence from SENP1 promoter were synthesized, and their topological structure was detected by circular dichroism analysis. G4 ligand TMPyP4 and G4 helicase G4R1 were used to detect the regulatory effect of promoter G4 on SENP1 transcriptional expression by using reporter assay and Western blot. Result: The -910~+226 region was found to be the core transcriptional regulatory region of SENP1 promoter. Sequence analysis showed the core region of SENP1 promoter is rich in G/C and contains G4 formation sequences. Circular dichroism analysis confirmed that the oligonucleotides of G4 formation sequence from SENP1 promoter form G4 structure. Reporter assay and Western blot showed that promoter G4 inhibited the transcriptional expression of SENP1. Conclusion: G4 exist in the core transcriptional regulatory region of SENP1 promoter and show negative regulation on SENP1 transcriptional expression, which provides new research ideas and experimental clues for revealing the mechanism of SENP1 in physiological and pathological processes.
High ATP level is beneficial to cyclic adenosine phosphate (cAMP) accumulation. Due to 3g/L-broth sodium pyruvate addition into the broth at 24h, cAMP final content achieved 4.13g/L which was enhanced 24.4% when compared with control, with obvious improved fermentation performance. NADH, ATP concentrations and activities of key enzymes contained in related metabolic pathways were detected to explain the mechanism. The results declare that pyruvate kinase was inhibited obviously by sodium pyruvate and the activities of key enzymes for cAMP synthesis (glucose-6-phosphate dehydrogenase, adenylosuccinate synthetase and adenylate cyclase) were enhanced greatly, which indicated that more carbon flux was directed into pentose phosphate pathway and purine synthesis pathway from glycolytic pathway for AMP production. In addition, activities of key enzymes in TCA (isocitrate dehydrogenase and succinate dehydrogenase), NADH/NAD +, ATP/AMP and respiratory chain activity were enhanced greatly which indicated that pyruvate activated energy metabolism to supply sufficient energy for cAMP synthesis. Sufficient energy supplement and enhanced carbon flux accounts for the physiological mechanism of higher cAMP accelerated by sodium pyruvate.
The control and prevention of the influenza virus is a challenging scientific question. The difficulty lies in its wide spread, variable antigen with high mutation rate, which enable it to escape the host’s immunity. The existing system for influenza surveillance is a hierarchical reporting system. Therefore, the influenza report was lagged behind 1-2 weeks. But influenza virus has a rapid mutation and transmission speed. So it is important to understand the influenza epidemic status in a real-time. The thesis focused on establishing a unified platform for influenza surveillance through the big-data minning of multi-source and the integration of a series of specific algorithm models.It includes three projects. The first one referred to the rapid estimation of influenza virus’s full-life monitoring in epidemic status, control, feedback, mutation and variation. Another project in the thesis was to systematically map the correlation between the dimension (such as time, geography and environment) and influenza virus through comprehensive analysis. Based the two project above, can gain an in-depth and comprehensive view of influenza forecasting warning system with characteristics of a safety, speediness, stability, accuration and real-time in mainland China.Systematic work has highlighted the challenge in its prevention and control, speaking to the necessity of extensive global influenza surveillance and local planning of the influenza.
Crinkling and necrosis-inducing protein is a class of special secreted cytoplasmic protein when phytophthora occurs, which interferes with the normal physiological metabolism and function of host cells. However, the relationship between its three-dimensional structure and infection mechanisms need to be further studied. The sequence of PcCRN20-C was amplified by PCR from cDNA of Phytophthora capsici LT1534, which is 783bp in length and encodes 261 amino acids. The expression vector of pET-28a-MBP-PcCRN20-C was constructed and transformed to Escherichia coli BL21(DE3). The recombinant protein was induced under optimal condition, subsequently purified by nickel chelate affinity chromatography, ion-exchange chromatography, molecular-exclusion chromatography and trypsin hydrolysis technology. The product identified as a specific band of 25kDa by SDS-PAGE, which is the same as predicted. Subsequently, crystals were grown with the sitting-drop vapour-diffusion method and diffracted by X-ray. As a result, the crystals of CRN were obtained in a way of protein crystallography, which set a foundation for further study on the connect of CRN structure with function to analyze the pathogenic mechanism of P. capsici at the molecular level.
Polyethylene glycol diglycidyl ether (PEGDGE), a double-functional epoxy reagent, was used to covalently immobilize marine lipase through cross-linking amino carrier LX-1000EA. The treated carrier behaved good effect in the covalent immobilization of lipase. After single factor screening and orthogonal experiment, the best conditions of crosslinking and immobilized is 0.75% concentration of crosslinking agent, crosslinking temperature 35℃, crosslinking time 3h, carrier quantity 1.25g, pH 9.0 and immobilization temperature 55℃, immobilization time of 1h. The enzymatic properties of LX-1000EA- PEGDGE immobilized enzyme were compared with that of free enzyme and glutaraldehyde crosslinked immobilized enzyme LX-1000HA-GA. Compared with free enzymes, the optimal reaction temperature of LX-1000EA-PEGDGE immobilized enzyme did not change; and similar with LX-1000HA-GA, the optimal reaction pH increased from 7.0 to 8.0. Under the optimal condition, the enzyme activity of LX-1000EA-PEGDGE reached 78.84U/g. Immobilization changed the acid-base tolerance of lipase, and the thermal stability and the operation stability were improved compared with free enzyme and LX-1000HA-GA immobilized enzyme. The immobilized enzyme exhibited excellent thermal stability,retaining 90% initial enzyme activity after 3h incubation at 60℃; the residual enzyme activity retained 50% of its original activity after 5 times of operation; the residual enzyme activity retained 60% of its original activity after preserved for 30 days at 4℃. The new crosslinking agent PEGDGE and organic amino carrier were combined for the first time to immobilize lipase,which provided technical support for more effective immobilization methods. It was also found that the cross-linking agent had a great impact on the properties of the immobilized enzyme.
With the development of sequencing technology, the number of known DNA sequences increase exponentially. In order to explore their biological functions more quickly, some new techniques have been developed. Most of these techniques require to construct plasmids in vitro, but the purification process of recombinant enzymes is complicated, transport and preservation are very difficult, which leads to high cost. Recently, researchers have developed simple and low-cost ways to assemble DNA in vivo. The research status, principle, advantages and disadvantages of all kinds of methods are reviewed and the trend is prospected in combination with practical work, hoping to provide a reference for the further research.
Coevolution is ubiquitous in nature. The natural enemies of bacteria and bacteria are a constant battle.Bacteria-phage system is a model material for studying coevolution. Bacteriophages, currently, there are two recognized models for the mechanism of bacteria-phage antagonistic coevolution: GFG model and MA model;corresponding to two models: ARD model and FSD model.The antagonistic coevolutionary kinetic model of bacteriophage was determined by time-shift assays. Long-tailed phages are the largest family of tailed phages. At present, the studies on bacteria-phage system coevolution mainly focus on the short tail and myotail phage and their hosts, while the bacteria-long tail phage coevolution has not been reported.
Peptide nucleic acid (PNA) is an oligonucleotide analog that replaces the sugar phosphate backbone with polypeptide backbone, and known as a third-generation antisense nucleic acid. The electrically neutral polypeptide backbone structure of PNA enables it to retain the high target affinity of the sugar phosphate chain oligonucleotide, and at the same time, it has stronger enzyme stability and thermal stability than the sugar phosphate backbone, which has become the hotspot in the research of oligonucleotide analogues. On the one hand, the rapid, effective and accurate detection performance of PNA on virus replication and mutation level makes it of great significance for further treatment of diseases. On the other hand, the life cycle of the virus is regulated by the PNA based on its sequence specificity and dose dependency at the gene level. Therefore, as to effective inhibit the survival and replication of the virus in the host cell. The latest progress and mechanism of PNA in the detection of different viruses and the treatment of viral diseases has been reviewed based on the literature of the past decade, which is expected to provide new guidances and ideas for the development of clinical products of peptide nucleic acids.
Bio-therapeutics refer to the macromolecular biological products prepared by biotechnology and applied in disease treatment. Because of their high complexity/heterogeneity on aspects of structure and activity, the scientific and rigorous generic names for bio-therapeutics are fundamental for identifying effective drug substances and regulating their life cycle. The International Nonproprietary Names (INN) Program was established by the World Health Organization (WHO) and coordinated to be a global standardization system for assigning nonproprietary names to medicinal substances.The origin and development of the INN system in particular the biologics INN system were introduced, the INN categories, substances and marketing situation were also illustrated to reflect the development trend of bio-therapeutics. Through detailed data analysis, the development process of global bio-therapeutics as well as related bio-technology were presented and reviewed from multiple perspectives, which could be harnessed as important reference significance for the R&Ds, technical standards, clinical applications and regulatory strategy considerations.
In the recent years, numerous studies highlighted the potential role of microecological drugs in treating multiple diseases and preserving host’s health. In this paper, all the data was extracted from Clarivate via Cortellis. The results of qualitative analysis and expert wisdom were as follows. Up to data, 142 kinds of microecological drugs have been identified and 49 kinds of them have been undergone clinical trials. The United States was far ahead of other countries with 70 percent of the amount in microecological drugs. The drug indications were focused on Clostridium difficile infection, inflammatory bowel disease and ulcerative colitis. The key players have established advanced experimental platforms for discovery and development of novel product candidates, while 4D pharma was a world leader in this field. There were seven drugs in phase 3 clinical development. Access to 303 microecological drugs deal records, the maximum transaction was $2.78 billion. In the future, microecological drugs may make a major breakthrough in cancer and nervous system diseases treatment.
With the development of life science and technology, innovative theories, techniques and clinical research of cell therapy are emerging. Cell therapy in China faces the favorable opportunity for development, and supervision has become an indispensable link to promote its industrialization. In recent years, the National Health Commission of the People’s Republic of China and China Food and Drug Administration have issued a series of policies and regulations to regulate the clinical research and clinical application of cell therapy. However, there are still no clear and detailed explanations on the issues of drug or technical supervision, supervisor and evaluation criteria. The basic content of cell therapy regulation dual-track system in Japan was clarified, its characteristics, and proposes policy recommendations for Chinese cell therapy supervision weresummarized.
In December 2018, the United States Department of Agriculture published the national bioengineered food information disclosure standard (detailed implementation rules), which detailed and improved the specific content of the bioengineered food information disclosure system in the United States, marking the basic establishment of the bioengineered food information disclosure system in the United States. The text mainly includes the following aspects: add the conditions of detectability, unify the exemption conditions of bioengineering food information disclosure, improve the form of bioengineering food information disclosure, set up voluntary labels, and the obligations of the subjects of bioengineering food information disclosure. Through analysis, it is found that under the premise of mandatory labeling, the United States still adheres to the principle of substantive equivalence to ensure the smooth transition of labeling system while protecting consumers’ right to know. In view of the chaos of GM food labeling in China, this paper draws lessons from the experience of the United States and puts forward Suggestions on how to improve GM food labeling system in China in terms of concept, labeling object, management institution and exemption.
With the rapid development of the world economy and the continuous growth of the population, energy shortage and environmental pollution has increasingly become the bottleneck of development. Microbial Fuel Cell (MFC) is a highly promising technology for sustainable wastewater treatment, which can directly convert the chemical energy stored in the pollutants into electric energy. In addition, the MFC technology also shows attractive prospects in sludge disposal, bioremediation, environmental monitoring, desalination and other aspects. Based on the Web of Science and Derwent Innovation database, the paper and patent data from 1990-2018 in the field of MFC was analyzed and the development trends, international distribution, research hotspots and technology fields were obtained. On this basis, the future development of MFC field was prospected, and the development of China’s MFC industrialization was proposed.
