Entry Stage Research Articles

PENERAPAN METODE QSPM TERHADAP PEMILIHAN STRATEGI DADAR BANJOER

Dadar Banjoer is one of the UMKM in the culinary field that was established in 2020. However, sales from Dadar Banjoer's business tend to decrease every month. This is due to the selection of strategies that are less effective and efficient so that Dadar Banjoer's business can be said to have lost in competitive competition with its competitors. Dadar Banjoer requires an effort to choose the right alternative strategy to be applied to his business in order to be able to compete again with its competitors. This research consists of 3 stages, the first is the entry stage by compiling the Internal Factors Evaluation and External Factors Evaluation matrix. The second is the matching stage, namely the making of the Internal External Matrix and the SWOT matrix which has the aim of determining alternative strategies. The third stage is the decision stage using the Quantitative Strategic Planning Matrix using an attractiveness score to determine the best alternative strategy. In this study, researchers used a qualitative method with a descriptive approach. The purpose of this research is applied research with data collection techniques by interview and observation. Initial interviews were conducted with shop owners and employees and then identified internal factors. Then, the second interview was conducted to determine the internal and external weights and ratings, and the third interview was conducted to determine the interest score used in the QSPM method to find the best alternative strategy.

Gallocatechin Gallate Inhibits the Replication of Pseudorabies Virus via Suppressing the Entry and Release Stages in Its Replication Cycle.

The pseudorabies virus is a widespread swine pathogen that has caused significant economic losses to the global pig industry. Due to the emergence of PRV variant strains in recent years, vaccines cannot provide complete protection against the infection of PRV. Therefore, the research on antiviral compounds is of great importance for PRV treatment. In this study, an EGFP-labeled PRV was used to screen anti-PRV compounds from 86 natural product extracts. Gallocatechin gallate was found to efficiently inhibit the replication of PRV with a half-maximal inhibitory concentration (IC50) of 0.41 μM. In addition, it was found that gallocatechin gallate was unable to directly inactivate PRV and had no effect on the attachment stage of PRV. However, it was found that gallocatechin gallate significantly suppressed the viral entry stage. Furthermore, it was found that the release stage of PRV was also significantly suppressed by gallocatechin gallate. Together, this study found that gallocatechin gallate could efficiently inhibit the replication of PRV by suppressing the entry and release stages of PRV, which will contribute to the development of a new therapeutic strategy against PRV infection.

Динаміка змін вмісту сполук кадмію та нітрат-іонів в екосистемі Прикарпаття

The purpose of the study was to form an algorithm for constant control of the content of cadmium and nitrate ions as an important component of environmental monitoring in the Ciscarpathia ecosystem. Materials and methods. The soils and drinking water of the plain, foothill and mountainous areas of the region were the object of research. The cadmium content was determined by atomic absorption spectrophotometry on a C-115 PC spectrophotometer. The concentration of nitrate ions in drinking water was determined potentiometrically using an ion-selective electrode. Results and discussion. The Ciscarpathia is a unique region of Ukraine with rich natural resources, diverse flora and fauna. At the same time, more than 500 industrial enterprises (more than 4% of the total area) of the chemical, energy, oil and gas, woodworking and other industries are located in the region. These enterprises cause a significant man-made load on all components of the natural environment. The ecological situation of the Ciscarpathian region is closely related to the state of soils and water resources. In this regard, it is appropriate to study and control the level of cadmium and nitrate compounds in the environment of the region. The study of the soils of the Carpathian region confirmed the growth of the cadmium toxic element, the content of which was by 1.3–1.5 times higher than the background indicators. It is determined that the level of nitrate ions in the drinking water of the plain zone exceeds the maximum permissible concentration by 1.5–2 times, and the physiological water completeness indicator – by 160–606 times; in the foothills and mountain zones the content of nitrates does not exceed the maximum permissible concentration, but it is by 35−253 times higher than the physiological water completeness indicator. The main stages of entry and accumulation of cadmium in the plant body have been analyzed. Conclusion. The results of our research made it possible to establish significant differences in the content of cadmium and nitrate ions in the soils and drinking water of different geographical zones of the Carpathian region. In particular, a significant number of the population living in the plains and foothills consumes water with a high content of nitrate ions and cadmium, which leads to an increase in the combined effect of these toxicants on living organisms. It is proposed to carry out constant monitoring of the level of toxicants in the ecosystem as an important component of environmental monitoring. The use of cultivated plants is recommended for cleaning the soil from cadmium contamination

Antiviral Activity of trans-Hexenoic Acid against Coxsackievirus B and Enterovirus A71.

Enterovirus infections are life-threatening viral infections which occur mainly among children and are possible causes of viral outbreak. Until now, treatment and management of infections caused by members of the genus Enterovirus largely depended on supportive care, and no antiviral medications are currently approved for the treatment of most of these infections. The urgency of discovering new therapeutic options for the treatment of enterovirus infection is increasing. In the present study, we identified that trans-2-hexenoic acid (THA), a natural product from a dietary source, possesses antiviral activity against coxsackievirus B (CVB) and enterovirus A71 (EV-A71) in a dose-dependent manner. We found that THA possesses antiviral activity at 50% effective concentrations (EC50) of 2.9 μM and 3.21 μM against CVB3 and EV-A71 infections, respectively. The time of addition assay revealed that THA inhibits both CVB3 and EV-A71 replication at the entry stage of infection. Additional results from this study further suggest that THA inhibits viral replication by blocking viral entry. Given that THA has received approval as a food additive, treatment of enterovirus infections with THA might be a safe therapeutic option or could pave the way for semisynthetic manufacturing of more antiviral drugs in the future.

Co-infecting phages impede each other's entry into the cell.

Bacteriophage lambda decides whether to pursue the lysogenic pathway based on the number of phages co-infecting the cell (multiplicity of infection, MOI). This strategy is believed to be a way for phages to infer the abundance of available bacterial hosts. However, the single-cell assessment would reliably reflect the environment only if the intracellular number of phages is proportional to the extracellular ratio of phages to bacteria. It is unknown whether this premise is true. Here, we show that co-infecting phages impede each other's entry into the cell, thus reducing the effective MOI that drives the decision. Using fluorescent labeling of phage capsids and DNA, we found that the intracellular number of phage genomes scales sublinearly with the number of phages adsorbed to the cell. Time-lapse measurements and mathematical modeling revealed that the entry probability per phage decreases with MOI, suggesting mutual interference between co-infecting phages at the entry stage. This effect likely reflects the phage-induced perturbations to the envelope integrity, ionic concentrations in the cytoplasm, and membrane potential of the infected cell. Since these perturbations are known to be MOI dependent, we reasoned that, the more phages infect the same cell, the more impeded their entries are. The degree to which phage entry is impeded successfully accounts for the different lysogenization frequencies measured in different infection media and recapitulates the heterogeneity in infection outcomes observed in individual cells. Altogether, our findings demonstrate the role played by entry dynamics in driving cell fate choice following lambda infection.

The Challenges and Issues Faced by the New Appointed Academic Staffs of the University in the Emerging Market

Purpose: The aim of this research is to explore the issues and challenges faced by the new appointed academic staffs of a public university in Malaysia. Theoretical framework: The appointment of the new academic staffs in the university offers a whole new paradigm and dynamic while could be beneficial for the universities’ ecosystem entirely. Among the benefits are contributing new ideas and implementation for improvement as well as fostering positive attitude within the environment. However, the staffs could encounter with various issues and challenges at the entry stage which could deter his or her development further. Design/methodology/approach: A qualitative approach is employed in this research where the academic staffs with less than 3 years’ working experience were interviewed in order to understanding the obstacles faced. The data gathered is analyzed using NVivo12 software. Findings: The findings of this research revealed that issues pertaining Key Performance Indicators (KPIs), teaching and learning which involved unfamiliar subjects and issue surrounding online classes, difficulties in publication and research component due to lack in knowledge, skills and experience, allyship in academic working environment as well as juggling between the demanding workload of teaching and administrative works with completion of the Postgraduate Diploma in Higher Education Learning and Teaching (PGDHELT) course. Research, Practical & Social implications: This research offers some practical significances particularly to the university’s management and the newly appointed academic staffs on board. The identification of issue and challenges among newly appointed staffs is significant in finding solutions. Originality/value: As a practical implication, this research paper sheds new light for both the Ministry of Higher Education (MOHE) Malaysia and the university’s management to formulate a handful and effective training and development program to smoothen the transition process of the new appointed academic staffs into the academic world in the university.

Developmentally Appropriate Prevention of Behavior and Emotional Problems and Fostering of Social and Emotional Skills in Elementary School – Overview of Program Theory and Measures of the Preventive Intervention Program Papilio-6to9

Children face increased demands for interpersonal as well as learning-related social skills, especially by the vulnerable stage of school entry, due to the more structured setting, new academic requirements, and the fact that children are supposed to interact successfully within a larger and heterogeneous peer group. Although a plethora of social-emotional learning (SEL) programs for elementary school students have been developed, there is a lack of empirically evaluated programs suitable for implementation in field-based settings, especially in Germany. The universal-selective, school-based prevention program Papilio-6to9 aims at facilitating the transition from preschool to elementary school, improving social-emotional competences, and preventing behavior and emotional problems. As a universal-selective prevention program, Papilio-6to9 includes all children in elementary school classes regardless of risk factors (universal prevention) whereby also children with risk factors are targeted without being stigmatised (selective prevention). The program targets elementary school children aged about six to nine and their teachers who receive a three-day training followed by two collegial supervisions to implement the program in and during regular school classes. Papilio-6to9 is part of an approach combining findings from developmentally appropriate practice, positive psychology, social-emotional learning, and developmentally appropriate prevention, and aligns with the early childhood education and care (ECEC)

Intentional dialogue as an effective impulse to creativity in the life of F.I. Chaliapin

The object of the study is Fyodor Ivanovich Chaliapin and his stage of entry into the world of art, which involved an intentional dialogue with recognized masters. This type of dialogue is characterized by mutual interest on the part of the interlocutors and a deep directional impact on the individual, encouraging emotional and intellectual self-development. Intentional dialogue, forming a space of participation, teaches to be awareness of being and inspires creativity. Disposed to conduct an intentional dialogue F.I. Chaliapin communicated with creative intelligentsia, quickly assimilating knowledge and adopting experience. Processed through the prism of his own creative self, he demonstrated his mastery at concerts and on the opera stage, winning recognition from audiences worldwide.

Identification of niclosamide as a novel antiviral agent against porcine epidemic diarrhea virus infection by targeting viral internalization

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there remain no effective drugs against PEDV infection. In this study, we utilized a recombinant PEDV expressing renilla luciferase (PEDV-Rluc) to screen potential anti-PEDV agents from an FDA-approved drug library in Vero cells. Four compounds were identified that significantly decreased luciferase activity of PEDV-Rluc. Among them, niclosamide was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index. It can efficiently inhibit viral RNA synthesis, protein expression and viral progeny production of classical and variant PEDV strains in a dose-dependent manner. Time of addition assay showed that niclosamide exhibited potent anti-PEDV activity when added simultaneously with or after virus infection. Furthermore, niclosamide significantly inhibited the entry stage of PEDV infection by affecting viral internalization rather than viral attachment to cells. In addition, a combination with other small molecule inhibitors of endosomal acidification enhanced the anti-PEDV effect of niclosamide in vitro. Taken together, these findings suggested that niclosamide is a novel antiviral agent that might provide a basis for the development of novel drug therapies against PEDV and other related pathogenic coronavirus infections.

Quassinoids from Eurycoma longifolia with antiviral activities by inhibiting dengue virus replication

BackgroundDengue caused by dengue virus (DENV) spreads rapidly around the world. However, there are no worldwide licensed vaccines or specific antivirals to combat DENV infection. Quassinoids are the most characteristic components of Eurycoma longifolia, which have been reported to display a variety of biological activities. However, whether quassinoids exert anti-DENV activities remains unknown. PurposeTo test the quassinoids of E. longifolia for their activity against DENV and to clarify the potential mechanisms. MethodsThe quassinoids from E. longifolia were isolated by chromatography techniques, and their chemical structures were elucidated by spectroscopic analysis. The anti-DENV activities of quassinoids on baby hamster kidney cells BHK-21 were determined by lactate dehydrogenase (LDH) assay. The synthesis of progeny virus was measured by plaque assay. The expression levels of envelope protein (E) and non-structural protein 1 (NS1) were evaluated by qRT-PCR, Western blot and immunofluorescence assays. Molecular docking was used to screen the potential targets of the most active quassinoid against DENV-2, and surface plasmon resonance analysis was employed to confirm the direct binding between the most active quassinoid and potential target. ResultsTwenty-four quassinoids, including three new quassinoids (1 − 3), were isolated from the ethanol extract of E. longifolia. Quassinoids 4, 5, 9, 11, 12, 15, 16, 17, 19 and 20 significantly reduced the LDH release at the stages of viral binding and entry or intracellular replication. Among them, 19 (6α-hydroxyeurycomalactone, 6α-HEL) exhibited the best anti-DENV-2 activities with an EC50 value of 0.39 ± 0.02 μM. Further experiments suggested that 6α-HEL remarkably inhibited progeny virus synthesis and mRNA and protein expression levels of E and NS1 of DENV-2. Time-of-drug-addition assay suggested that 6α-HEL inhibited intracellular replication of DENV-2 at an early stage. Moreover, 6α-HEL was shown to interact with NS5-RdRp domain at a binding affinity of -8.15 kcal/mol. SPR assay further verified 6α-HEL bound to RdRp protein with an equilibrium dissociation constant of 1.49 × 10−7 M. ConclusionTen quassinoids from E. longifolia showed anti-DENV activities at processes of virus binding and entry or intracellular replication. The most active quassinoid 6α-HEL exerts the anti-DENV-2 activities at intracellular replication stage by directly targeting the NS5-RdRp protein. These results suggest that 6α-HEL could be a promising candidate for the treatment of DENV-2 infection.

КОНЦЕПТУАЛЬНІ ОСНОВИ РОЗРОБКИ МАРКЕТИНГОВИХ СТРАТЕГІЙ ВИХОДУ ПІДПРИЄМСТВ НА ЗОВНІШНІ РИНКИ: СУТНІСТЬ ТА ЗНАЧЕННЯ ДЛЯ ВІДНОВЛЕННЯ УКРАЇНСЬКОЇ ЕКОНОМІКИ

The article examines theoretical and methodological approaches and formulates practical recommendations for the development of a marketing strategy for an enterprise entering foreign markets, which will ensure its sustainability and competitive development. A generalization of scientific views on the definition of the essence of the concept of "marketing strategy" was carried out in the context of the process of the enterprise entering foreign sales markets. The main external and internal conditions affecting the company's ability to enter target foreign markets, as well as the specifics of the formation of its strategic behavior on them, are singled out and analyzed. The significance of the analysis of the sources of capital formation of the enterprise when planning the strategy of entering international markets is emphasized. The need for a comprehensive approach to the assessment of foreign markets to ensure the success of entering them is substantiated. The author's algorithm for the formation of a marketing strategy in the event of a decision to enter a specific foreign market by the enterprise is proposed, which includes 12 main stages. The key tasks for the analysis of the available resources and capabilities of the enterprise in order to assess the readiness to enter the selected target foreign market have been determined. To ensure success when entering new markets, it is important to understand what resources the company will attract for the implementation of its international activities and in which business units it will invest its capital. The main principles of determining the positioning strategy for an enterprise entering the foreign market are characterized. On the basis of the generalization of theoretical approaches, recommendations for the formation of the optimal marketing complex of the enterprise, which best meets the needs of target consumers at the stage of the enterprise's entry into foreign sales markets, are substantiated and formed. The most promising areas for Ukrainian business to enter foreign markets are characterized. The author's vision of effective marketing tools for the penetration of domestic enterprises into foreign markets in the conditions of the digital economy is presented.

Biosimilars and Heterogeneous Technological Trajectories in the Argentine Biopharmaceutical Industry.

This paper will review the strategies and learning trajectories followed to tap the opportunities opened by the successive waves of biotechnologies: early imitators followed by late imitators in the first generation of biosimilars (erythropoietin, insulins, interferons), and then sequential entry and skipping stages during the second generation (monoclonal antibodies).

The Role of Cytosolic Lipid Droplets in Hepatitis C Virus Replication, Assembly, and Release.

The hepatitis C virus (HCV) causes chronic hepatitis by establishing a persistent infection. Patients with chronic hepatitis frequently develop hepatic cirrhosis, which can lead to liver cancer-the progressive liver damage results from the host's immune response to the unresolved infection. The HCV replication process, including the entry, replication, assembly, and release stages, while the virus circulates in the bloodstream, it is intricately linked to the host's lipid metabolism, including the dynamic of the cytosolic lipid droplets (cLDs). This review article depicts how this interaction regulates viral cell tropism and aids immune evasion by coining viral particle characteristics. cLDs are intracellular organelles that store most of the cytoplasmic components of neutral lipids and are assumed to play an increasingly important role in the pathophysiology of lipid metabolism and host-virus interactions. cLDs are involved in the replication of several clinically significant viruses, where viruses alter the lipidomic profiles of host cells to improve viral life cycles. cLDs are involved in almost every phase of the HCV life cycle. Indeed, pharmacological modulators of cholesterol synthesis and intracellular trafficking, lipoprotein maturation, and lipid signaling molecules inhibit the assembly of HCV virions. Likewise, small-molecule inhibitors of cLD-regulating proteins inhibit HCV replication. Thus, addressing the molecular architecture of HCV replication will aid in elucidating its pathogenesis and devising preventive interventions that impede persistent infection and prevent disease progression. This is possible via repurposing the available therapeutic agents that alter cLDs metabolism. This review highlights the role of cLD in HCV replication.

Business Educators Perception of Digital Skills Required by Office Technology and Management Students for Employability

The management of any organization be it private or public expects its employees to possess relevant digital skills to perform effectively in this dispensation. The study examined business educators’ perception of digital skills required by Office Technology and Management students for employability. Based on the objectives of the study, two research questions guided the study. The study adopted descriptive survey research design. The population of the study consisted of 111 business educators drawn from Polytechnics in North-East Nigeria. The entire population was studied, no sample since the population was manageable. A structured questionnaire developed on a five point Likert rating scale tagged ‘’Business Educators perception of Digital Skills Required by Office Technology and Management students for Employability’’ (BEPDSOTMSE) with 23 items was used to elicit data from the respondents. The instrument was validated by three specialists in the field. The reliability of the instrument was determined using Cronbrach Alpha which yielded a co-efficient of 0.77 signifying that the instrument was reliable. Data collected were analyzed using mean and standard deviation. The findings of the study revealed that all the skills were highly required for employability by OTM students’ based on the perception of business educators. The researchers recommended among others that Management of institutions should ensure that orientation be given to prospective candidates which is vital in the early stage of entry into the Polytechnics about the skills required for employment.

Molecular mechanism of antibody neutralization of coxsackievirus A16

Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies.

An Exploration Study on Hybrid Vegetable Crops in Kulgam District of Jammu and Kashmir

Seed is considered as the most fundamental and important ingredient for longterm agriculture. All other inputs respond to seed quality to a considerable amount, and quality seed alone contributes 20 percent to overall yield, depending on the crop and can be increased to 45 percent with efficient management of other inputs. The Present study is aimed to evaluate the effects of gender for cultivation of hybrid vegetable crops in Kulgam district of Jammu and Kashmir. Well structured questionnaire were designed as an instrument to collect primary data from the respondent, the questionnaire were distributed to 100 respondents on random basis, all the questionnaires were collected back during survey but at data entry stage it was found that 8 questionnaires were incomplete and hence eliminated from the present study, therefore the final sample size of present study is 92 farmer. Hence, the empirical results and findings are discussed in the present work.

Hyperpigmentation Inhibits Early Skeletal Muscle Development in Tengchong Snow Chicken Breed.

Tengchong snow, which has white feathers and black meat, is one of the most important black-bone chicken breeds and a genetic treasure of black food in China. Although the black meat traits are dominant, there are some chickens with white meat traits born in the process of folk selection and breeding. The purpose of this study was to compare the differences in skeletal muscle development between Tengchong snow black meat chickens (BS) and white meat chickens (WS), as well as whether excessive melanin deposition has an effect on skeletal muscle development. The BS and WS groups were selected to determine their muscle development difference at stages of 1, 7, 14, 21, and 42 days, using histological stain methods to analyze the development and composing type of breast and leg muscle fibers, as well as the count of melanin in BS muscle fibers. Finally, we were validated key candidate genes associated with muscle development and melanin synthesis. The results showed that BS breast muscle development was inhibited at 7, 14, and 21 days, while the leg muscle was inhibited at 7, 14, 21, and 42 days, compared to WS. Melanin deposition was present in a temporal migration pattern and was greater in the leg muscles than in the breast muscles, and it focused around blood vessels, as well as the epithelium, perimysium, endomysium, and connective tissue. Additionally, melanin produced an inhibitory effect similar to MSTN during skeletal muscle fiber development, and the inhibition was strongest at the stage of melanin entry between muscle fibers, but the precise mechanisms need to be confirmed. This study revealed that melanin has an inhibitory effect on the early development of skeletal muscle, which will provide new insights into the role of melanin in the black-boned chicken and theoretical references for the future conservation and utilization of black-boned chicken.

Inhibitory Potential of Chromene Derivatives on Structural and Non-Structural Proteins of Dengue Virus.

Dengue fever is a mosquito-borne viral disease that has become a serious health issue across the globe. It is caused by a virus of the Flaviviridae family, and it comprises five different serotypes (DENV-1 to DENV-5). As there is no specific medicine or effective vaccine for controlling dengue fever, there is an urgent need to develop potential inhibitors against it. Traditionally, various natural products have been used to manage dengue fever and its co-morbid conditions. A detailed analysis of these plants revealed the presence of various chromene derivatives as the major phytochemicals. Inspired by these observations, authors have critically analyzed the anti-dengue virus potential of various 4H chromene derivatives. Further, in silico, in vitro, and in vivo reports of these scaffolds against the dengue virus are detailed in the present manuscript. These analogues exerted their activity by interfering with various stages of viral entry, assembly, and replications. Moreover, these analogues mainly target envelope protein, NS2B-NS3 protease, and NS5 RNA-dependent RNA polymerase, etc. Overall, chromene-containing analogues exerted a potent activity against the dengue virus and the present review will be helpful for the further exploration of these scaffolds for the development of novel antiviral drug candidates.

Simulation and accuracy analysis of orbit determination for TianQin using SLR data

TianQin project is a space gravitational wave detection project initiated by Sun Yat-sen University. It has high requirements for detectors’ orbit accuracy in the stages of orbit entry and scientific experiment operation. We obtain the different combinations of radial position errors and along-track velocity errors after analyzing the detectors orbit errors according to the stability requirements of TianQin constellation. Satellite laser ranging (SLR) is the space geodetic technique with the highest accuracy of range measurement, which is a commonly used method for satellite orbit determination. This paper uses solely simulated SLR data to determinate the precise orbit of TianQin detectors. We examine how the number of stations, the distribution of stations, and the measurement errors affect the SLR-only orbit determination accuracy. The results demonstrate that: (a) for the 7 days solution with 1 cm random errors and 0.5 cm systematic errors of SLR simulations, the average orbit determination accuracy of TianQin detectors is increasing from 27.37 m when using 5 Chinese stations to 9.34 m when using 6 Chinese stations. (b) The orbit determination accuracy can be significantly improved by optimizing the distribution of stations, which is increasing from 9.34 m for regional distribution to 1.75 m for global distribution when the number of stations is six. (c) When employing 6 Chinese stations, each 1 cm of random errors results in a deterioration in position accuracy by 19% and in velocity accuracy by 23%, each 1 cm of systematic errors affects 14% for position accuracy and 15% for velocity accuracy, respectively. While the impact of measurement errors on the orbit determination accuracy is aggravated when using 6 global distribution stations, which are 35% and 33% of 1 cm random errors and 17% and 20% of 1 cm systematic errors, respectively.

SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules.

Antiviral agents are needed for the treatment of SARS-CoV-2 infections and to control other coronavirus outbreaks that may occur in the future. Here we report the identification and characterization of RNA-binding compounds that inhibit SARS-CoV-2 replication. The compounds were detected by screening a small library of antiviral compounds previously shown to bind HIV-1 or HCV RNA elements with a live-virus cellular assay detecting inhibition of SARS-CoV-2 replication. These experiments allowed detection of eight compounds with promising anti-SARS-CoV-2 activity in the sub-micromolar to micromolar range and wide selectivity indexes. Examination of the mechanism of action of three selected hit compounds excluded action on the entry or egress stages of the virus replication cycle and confirmed recognition by two of the molecules of conserved RNA elements of the SARS-CoV-2 genome, including the highly conserved S2m hairpin located in the 3'-untranslated region of the virus. While further studies are needed to clarify the mechanism of action responsible for antiviral activity, these results facilitate the discovery of RNA-targeted antivirals and provide new chemical scaffolds for developing therapeutic agents against coronaviruses.