scholarly journals Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution

2021 ◽  
Author(s):  
Danilo Rosa Nunes ◽  
Carla Torres Braconi ◽  
Louisa Ludwig-Begall ◽  
Clarice Weis Arns ◽  
Luiz Mario Ramos Janini ◽  
...  
Keyword(s):  
Clustering Analysis ◽  
Rna Virus ◽  
Point Mutations ◽  
Linear Perspective ◽  
Global Public Health ◽  
Health Crisis ◽  
Viral Spread ◽  
Novel Variants ◽  
Directional Evolution ◽  
The Usa

Nearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of not previously reported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution (i), and a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains (ii).

scholarly journals Role of renin-angiotensin-aldosterone system in the interaction with coronavirus SARS-CoV-2 and in the development of strategies for prevention and treatment of new coronavirus infection (COVID-19)

2020 ◽  
Vol 26 (3) ◽  
pp. 248-262
Author(s):  
A. Ya. Fisun ◽  
D. V. Cherkashin ◽  
V. V. Tyrenko ◽  
C. V. Zhdanov ◽  
C. V. Kozlov
Keyword(s):  
Rna Virus ◽  
Angiotensin Receptor Blockers ◽  
Protein S ◽  
Active Phase ◽  
Scientific Data ◽  
Global Public Health ◽  
Cellular Mechanisms ◽  
Health Crisis ◽  
Early Results ◽  
Transmembrane Serine Protease

The 2019 coronavirus pandemic (COVID-19), due to the new SARS-CoV-2 virus, represents the greatest global public health crisis and an unprecedented challenge to find effective ways to prevent and treat. In the active phase of a pandemic, early results allow these preventive measures to be implemented on a scale compatible with the pandemic. If the results are convincing, their value will be difficult to overestimate, since additional one or two outbreaks of this infection are expected. Clinical data is emerging rapidly from a large number of people afflicted with SARS-CoV-2, which should provide clinicians with accurate evidence of the effectiveness of different preventive and treatment methods. In particular, an active search is underway for cellular mechanisms that SARS-CoV-2 uses to penetrate tissues. These include information about the receptor of the angiotensin-converting enzyme receptor (ACE 2). SARS-CoV-2, a single-stranded envelope RNA virus, attaches to cells via a viral spike (S) protein that binds to the ACE 2. After binding to the receptor, the viral particle uses the receptors of the host cell and endosomes to enter the cells. Human type transmembrane serine protease 2 (TMPRSS 2) facilitates penetration into the cell via protein S. Once inside the cell, viral polyproteins are synthesized that encode the replicate transcriptase complex. The virus then synthesizes RNA through its RNA-dependent RNA polymerase. Structural proteins are synthesized leading to the completion of the assembly and release of viral particles. These stages of the virus life cycle provide potential targets for drug therapy. Current clinical and scientific data do not support discontinuation of ACE inhibitors or angiotensin receptor blockers in patients with COVID-19, and an ongoing discussion is addressed in this review.

scholarly journals Development and Evaluation of a Multiplex SARS-CoV-2 RT-ddPCR, Applicable to Respiratory and Wastewater Samples

2021 ◽  
Author(s):  
Laura A. E. Van Poelvoorde ◽  
Mathieu Gand ◽  
Marie-Alice Fraiture ◽  
Sigrid C. J. De Keersmaecker ◽  
Bavo Verhaegen ◽  
...  
Keyword(s):  
Reverse Transcription ◽  
Diagnostic Testing ◽  
Point Mutations ◽  
Digital Pcr ◽  
Clinical Samples ◽  
Health Crisis ◽  
Viral Spread ◽  
Reliable Quantification ◽  
Wastewater Samples ◽  
And Control

Abstract The worldwide emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2019 has highlighted the importance of rapid and reliable diagnostic testing to prevent and control the viral transmission. The monitoring of the viral spread can be performed using individual diagnostics in clinical samples and global detection of SARS-CoV-2 in wastewater samples. Reverse-transcription droplet digital PCR (RT-ddPCR) offers an attractive platform for absolute RNA quantification in comparison to the gold standard reverse transcription quantitative PCR (RT-qPCR) that only yields relative quantification results. To avoid inaccurate results due to false negatives caused by polymorphisms or point mutations that can possibly compromise the accuracy of the diagnostic tests, a multiplex RT-ddPCR method was developed by combining previously published SARS-CoV-2 detection RT-qPCR assays targeting well-conserved ORF1a and RdRp genes. These assays were successfully evaluated in silico for their inclusivity using GISAID sequences from the beginning of November 2020 to the end of February 2021. The sensitivity and specificity of the new RT-ddPCR method was evaluated and its applicability on both clinical and wastewater samples was illustrated. In conclusion, a reliable and sensitive multiplex one-step RT-ddPCR assay for reliable quantification of SARS-CoV-2 RNA in clinical and wastewater samples was developed and assessed, providing a key tool for the current health crisis.

scholarly journals A Comprehensive Molecular Epidemiological Analysis of SARS-CoV-2 Infection in Cyprus from April 2020 to January 2021: Evidence of a Highly Polyphyletic and Evolving Epidemic

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1098
Author(s):  
Andreas C. Chrysostomou ◽  
Bram Vrancken ◽  
George Koumbaris ◽  
George Themistokleous ◽  
Antonia Aristokleous ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Diagnostic Testing ◽  
Genomic Sequences ◽  
Clinical Samples ◽  
Global Public Health ◽  
Health Crisis ◽  
The Czech Republic ◽  
Epidemiological Analysis ◽  
The United Kingdom ◽  
The Usa

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in an extraordinary global public health crisis. In early 2020, Cyprus, among other European countries, was affected by the SARS-CoV-2 epidemic and adopted lockdown measures in March 2020 to limit the initial outbreak on the island. In this study, we performed a comprehensive retrospective molecular epidemiological analysis (genetic, phylogenetic, phylodynamic and phylogeographic analyses) of SARS-CoV-2 isolates in Cyprus from April 2020 to January 2021, covering the first ten months of the SARS-CoV-2 infection epidemic on the island. The primary aim of this study was to assess the transmissibility of SARS-CoV-2 lineages in Cyprus. Whole SARS-CoV-2 genomic sequences were generated from 596 clinical samples (nasopharyngeal swabs) obtained from community-based diagnostic testing centers and hospitalized patients. The phylogenetic analyses revealed a total of 34 different lineages in Cyprus, with B.1.258, B.1.1.29, B.1.177, B.1.2, B.1 and B.1.1.7 (designated a Variant of Concern 202012/01, VOC) being the most prevalent lineages on the island during the study period. Phylodynamic analysis showed a highly dynamic epidemic of SARS-CoV-2 infection, with three consecutive surges characterized by specific lineages (B.1.1.29 from April to June 2020; B.1.258 from September 2020 to January 2021; and B.1.1.7 from December 2020 to January 2021). Genetic analysis of whole SARS-CoV-2 genomic sequences of the aforementioned lineages revealed the presence of mutations within the S protein (L18F, ΔH69/V70, S898F, ΔY144, S162G, A222V, N439K, N501Y, A570D, D614G, P681H, S982A and D1118H) that confer higher transmissibility and/or antibody escape (immune evasion) upon the virus. Phylogeographic analysis indicated that the majority of imports and exports were to and from the United Kingdom (UK), although many other regions/countries were identified (southeastern Asia, southern Europe, eastern Europe, Germany, Italy, Brazil, Chile, the USA, Denmark, the Czech Republic, Slovenia, Finland, Switzerland and Pakistan). Taken together, these findings demonstrate that the SARS-CoV-2 infection epidemic in Cyprus is being maintained by a continuous influx of lineages from many countries, resulting in the establishment of an ever-evolving and polyphyletic virus on the island.

Preparation and Antitubercular Activities of Palindromic Hydrazinecarbothioamides and Carbonothioic Dihydrazides

2019 ◽  
Vol 16 (11) ◽  
pp. 1202-1210 ◽  
Author(s):  
Michael Joseps Hearn ◽  
Gwendolyn Towers ◽  
Michael Henry Cynamon
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Virulent Strain ◽  
Chemotherapeutic Agents ◽  
Disc Diffusion ◽  
Global Public Health ◽  
Health Crisis ◽  
Chemical Structures ◽  
Public Health Crisis ◽  
Zones Of Inhibition ◽  
Diffusion Assay

Background:With approximately one-third of the world’s population infected, tuberculosis continues to be a global public health crisis. The rise of strains that are unusually virulent or highly resistant to current drugs is a cause of special concern, prompting research into new classes of compounds, as well as the re-evaluation of known chemotherapeutic agents.Objectives:The antimycobacterial activities associated with some recently-reported thiocarbonyl compounds kindled our interest in the synthesis of substituted hydrazinecarbothioamides (3) and carbonothioic dihydrazides (4), with the aim of investigating their potential in antitubercular drug design and discovery.Methods:In the present study, the title compounds 3 and 4 were prepared by the condensation of hydrazines with isothiocyanates in reactions readily controlled by stoichiometry, temperature and solvent. The compounds were assessed against Mycobacterium bovis BCG in Kirby-Bauer disc diffusion, and minimum inhibitory concentrations were determined against the virulent strain M. tuberculosis Erdman.Results:The chemical structures of these thermally stable compounds were determined by IR, 1HNMR, 13C-NMR, high-resolution mass spectrometry and elemental analysis. In the Kirby-Bauer disc diffusion assay, some of the compounds showed substantial diameters of inhibition against BCG. In some cases, the zones of inhibition were so large that no growth at all was observed on the assay plates. Against M. tuberculosis Erdman, several of the compounds showed significant activities. Compound 3h was the most active, demonstrating a minimum inhibitory concentration of 0.5 µg/mL.Conclusion:We found that the title compounds may be prepared conveniently in excellent purity and good yields. They are readily identified on the basis of their characteristic spectra. Some members of this class showed significant activities against mycobacteria. We conclude that further work will be warranted in exploring the antitubercular properties of these compounds.

scholarly journals The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1828
Author(s):  
Jared Kirui ◽  
Yara Abidine ◽  
Annasara Lenman ◽  
Koushikul Islam ◽  
Yong-Dae Gwon ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Rna Virus ◽  
Ectopic Expression ◽  
Point Mutations ◽  
Cell Entry ◽  
Target Cells ◽  
Human Hepatoma Cells ◽  
Chikv Infection ◽  
Phosphatidylserine Receptor

Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

scholarly journals A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu Guo ◽  
Lisu Huang ◽  
Guangshun Zhang ◽  
Yanfeng Yao ◽  
He Zhou ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Complex Structure ◽  
Neutralizing Antibody ◽  
Economic Consequences ◽  
Binding Motif ◽  
Global Public Health ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Monkey Model ◽  
Therapeutic Outcomes

AbstractCOVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.

scholarly journals Citation: Cabezas-González, M.; Casillas-Martín, S.; García-Valcárcel Muñoz-Repiso, A. Basic Education Students’ Digital Competence in the Area of Communication: The Influence of Online Communication and the Use of Social Networks. Sustainability 2021, 13, 4442. https://doi.org/10.3390/su13084442

2021 ◽  
Vol 13 (8) ◽  
pp. 4442
Author(s):  
Marcos Cabezas-González ◽  
Sonia Casillas-Martín ◽  
Ana García-Valcárcel Muñoz-Repiso
Keyword(s):  
Social Networks ◽  
Basic Education ◽  
Online Communication ◽  
Quantitative Methodology ◽  
Global Public Health ◽  
Digital Competence ◽  
Education Students ◽  
Cross Sectional ◽  
Health Crisis ◽  
Use Of Social Media

The global public health crisis unleashed by the COVID-19 pandemic has made it clear that digital competence in education is no longer an option, but a necessity. Online communication with friends using social networks is an activity in which young people very frequently and at increasingly early ages engage. This article presents the results of a study analyses digital-competence levels in the area of communication of Spanish basic-education students (aged 12–16) and establishes whether online communication with friends and the use of social media impact it. A quantitative methodology with a descriptive and cross-sectional design was used. The sample comprised 807 students, and data collection was based on a problem-solving test. Findings show that students who use online communication with their friends very often and that those who use social networks a lot have lower levels of digital competence. Education centres should reflect on this in order to implement curricular programs that may strengthen this type of competence.

scholarly journals The Potential Use of Vitamin C to Prevent Kidney Injury in Patients with COVID-19

Diseases ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 46
Author(s):  
Feng Xu ◽  
Yawei Wen ◽  
Xinge Hu ◽  
Tiannan Wang ◽  
Guoxun Chen
Keyword(s):  
Vitamin C ◽  
Distress Syndrome ◽  
Kidney Injury ◽  
Mortality Rates ◽  
Protective Effects ◽  
Global Public Health ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Renal Functions ◽  
Potential Use

The newly found SARS-CoV-2 has led to the pandemic of COVID-19, which has caused respiratory distress syndrome and even death worldwide. This has become a global public health crisis. Unfortunately, elders and subjects with comorbidities have high mortality rates. One main feature of COVID-19 is the cytokine storm, which can cause damage in cells and tissues including the kidneys. Here, we reviewed the current literature on renal impairments in patients with COVID-19 and analyzed the possible etiology and mechanisms. In addition, we investigated the potential use of vitamin C for the prevention of renal injury in those patients. It appears that vitamin C could be helpful to improve the outcomes of patients with COVID-19. Lastly, we discussed the possible protective effects of vitamin C on renal functions in COVID-19 patients with existing kidney conditions.

Synergising International Public Health Law and International Disaster Law

2020 ◽  
pp. 1-11
Author(s):  
Pratik DIXIT
Keyword(s):  
Public Health ◽  
International Health ◽  
Health Law ◽  
Global Public Health ◽  
Public Health Law ◽  
Health Crisis ◽  
Response Strategies ◽  
Public Health Crisis ◽  
International Public Health ◽  
Health Regulations

There is no time more opportune to review the workings of the International Health Regulations (IHR) than the present COVID-19 crisis. This article analyses the theoretical and practical aspects of international public health law (IPHL), particularly the IHR, to argue that it is woefully unprepared to protect human rights in times of a global public health crisis. To rectify this, the article argues that the IHR should design effective risk reduction and response strategies by incorporating concepts from international disaster law (IDL). Along similar lines, this article suggests that IDL also has a lot to learn from IPHL in terms of greater internationalisation and institutionalisation. Institutionalisation of IDL on par with IPHL will provide it with greater legitimacy, transparency and accountability. This article argues that greater cross-pollination of ideas between IDL and IPHL is necessary in order to make these disciplines more relevant for the future.

THE RELEVANCE OF RT-PCR TEST TO THE INFECTION WITH SARS-COV-2 VIRUS.

2021 ◽  
pp. 2-4
Author(s):  
Sujan Narayan Agrawal
Keyword(s):  
Rna Virus ◽  
High Sensitivity ◽  
Standard Test ◽  
Laboratory Method ◽  
Global Public Health ◽  
Rt Pcr ◽  
Mild Disease ◽  
Pathogenic Virus ◽  
Appropriate Treatment ◽  
Tract Infections

It is now a fact that the disease COVID-19 is caused by the virus SARC-CoV-2. This virus is a member of the Coronavridae family and Coronavirinae subfamily. It is an RNA virus. The outer surface of the virus has characteristic projections which are club-shaped or spiked. This gives virion a typical look like the solar corona hence the name coronavirus. These viruses primarily cause respiratory tract infections which may range from mild disease to lethal one. The recent outbreak caused by this virus has posed a great threat to global public health and is now declared a pandemic. It is of vital importance to have a rapid and accurate identication of the pathogenic virus. This will help in selecting appropriate treatment, saving people’s lives, and preventing its spread. The RT-PCR is regarded as the gold standard test for the molecular diagnosis of this viral infection. It has got high sensitivity and specicity. This review summarises the characteristics of the virus and the laboratory method of its detection by RT-PCR.

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