scholarly journals SARS-CoV-2: a view on its origin, transmission, genetic characteristics and pathogenicity

2021 ◽  
Vol 13 (6) ◽  
pp. e7567
Author(s):  
Kassyo Lenno Sousa Dantas ◽  
Wilian Reis Rosário ◽  
Alice Gabrielly Landim Lima ◽  
Antonio Ycaro Rodrigues Lucena ◽  
Thallyson Jose Dourado de Sousa ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Life Support ◽  
Genomic Sequence ◽  
Antiviral Agents ◽  
Unknown Origin ◽  
Symptomatic Treatment ◽  
Etiologic Agent ◽  
New Drugs ◽  
Therapeutic Interventions ◽  
Genetic Characteristics

Objective: To describe the origin, transmission, morphological and genetic characteristics of SARS-CoV-2 and its pathogenicity mechanisms. Bibliographic review: At the end of December 2019, health centers in Wuhan, Hubei-China province, observed several cases of pneumonia of unknown origin, associated with a new etiologic agent, a virus, with a similar, but distinct, genomic sequence of SARS-CoV and MERS-CoV, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most common symptoms at the beginning of the infection are fever, cough, fatigue, olfactory and taste disorders; on the other hand, severe cases include pulmonary impairment and hypoxia. Currently, there are no antiviral agents with proven clinical efficacy and vaccination occurs in slow steps in most countries, with symptomatic treatment and life support still being the main therapeutic interventions available. Final considerations: SARS-CoV-2 presents itself as one of the biggest public health problems in the world nowadays. The search for new drugs to treat COVID-19 is constant, however, so far no new drug is available for use with 100% proven clinical efficacy.

scholarly journals Modern approaches to drug treatment for vestibular vertigo

2021 ◽  
Vol 13 (1) ◽  
pp. 101-106
Author(s):  
M. V. Zamergrad ◽  
S. V. Morozova
Keyword(s):  
Patient Adherence ◽  
Beta Blockers ◽  
Antiviral Agents ◽  
Symptomatic Treatment ◽  
New Drugs ◽  
Dopamine Antagonists ◽  
Prolonged Release ◽  
Release Formulation ◽  
Hunt Syndrome ◽  
Vestibular Vertigo

In recent years, some progress has been achieved in elaborating the algorithms and standards for the treatment of many conditions accompanied by vertigo. The current possibilities of treating vestibular vertigo consist of a gradually expanding arsenal of symptomatic and pathogenetic drugs. Among the drugs used for the symptomatic treatment of vestibular vertigo, there are vestibular suppressants (antihistamines, benzodiazepines, and calcium antagonists) and antiemetics (dopamine antagonists and serotonin 5-HT3 receptor antagonists). The paper discusses the possibilities of using betahistine and vitamin D as pathogenetic agents for recurrent benign paroxysmal positional vertigo; diuretics, betahistine (including the new prolonged release formulation Betaserc® Long), glucocorticoids, and gentamicin for Meniere's disease; triptans, beta-blockers, tricyclic antidepressants, and anticonvulsants for vestibular migraine; glucocorticoids, antiviral agents, and drugs that accelerate vestibular compensation for acute unilateral peripheral vestibulopathy (vestibular neuritis and Ramsey Hunt syndrome).The emergence of new drugs, as well as the design of new dosage forms that enhance patient adherence to the prescribed treatment, can improve quality of life in patients suffering from diseases that have recently led to long-term disability or even incapacitation.

scholarly journals Genomic Diversity of Burkholderia pseudomallei Clinical Isolates: Subtractive Hybridization Reveals a Burkholderia mallei-Specific Prophage in B. pseudomallei 1026b

2004 ◽  
Vol 186 (12) ◽  
pp. 3938-3950 ◽  
Author(s):  
David DeShazer
Keyword(s):  
Suppression Subtractive Hybridization ◽  
Burkholderia Pseudomallei ◽  
Genomic Sequence ◽  
Subtractive Hybridization ◽  
Etiologic Agent ◽  
Polyclonal Antiserum ◽  
Genomic Diversity ◽  
Clinical Isolates ◽  
Immunogold Electron Microscopy ◽  
Burkholderia Mallei

ABSTRACT Burkholderia pseudomallei is the etiologic agent of the disease melioidosis and is a category B biological threat agent. The genomic sequence of B. pseudomallei K96243 was recently determined, but little is known about the overall genetic diversity of this species. Suppression subtractive hybridization was employed to assess the genetic variability between two distinct clinical isolates of B. pseudomallei, 1026b and K96243. Numerous mobile genetic elements, including a temperate bacteriophage designated φ1026b, were identified among the 1026b-specific suppression subtractive hybridization products. Bacteriophage φ1026b was spontaneously produced by 1026b, and it had a restricted host range, infecting only Burkholderia mallei. It possessed a noncontractile tail, an isometric head, and a linear 54,865-bp genome. The mosaic nature of the φ1026b genome was revealed by comparison with bacteriophage φE125, a B. mallei-specific bacteriophage produced by Burkholderia thailandensis. The φ1026b genes for DNA packaging, tail morphogenesis, host lysis, integration, and DNA replication were nearly identical to the corresponding genes in φE125. On the other hand, φ1026b genes involved in head morphogenesis were similar to head morphogenesis genes encoded by Pseudomonas putida and Pseudomonas aeruginosa bacteriophages. Consistent with this observation, immunogold electron microscopy demonstrated that polyclonal antiserum against φE125 reacted with the tail of φ1026b but not with the head. The results presented here suggest that B. pseudomallei strains are genetically heterogeneous and that bacteriophages are major contributors to the genomic diversity of this species. The bacteriophage characterized in this study may be a useful diagnostic tool for differentiating B. pseudomallei and B. mallei, two closely related biological threat agents.

scholarly journals Focus on the spondyloarthritides. Can earlier diagnosis change the course of the disease?

2013 ◽  
pp. 277-283
Author(s):  
Domenico Galasso ◽  
Giovanni Forte ◽  
Norma Marigliano
Keyword(s):  
Strong Association ◽  
Human Leukocyte ◽  
Unknown Origin ◽  
Lower Limbs ◽  
Inflammatory Rheumatic Diseases ◽  
Genetic Characteristics ◽  
Leukocyte Antigen ◽  
Musculoskeletal Manifestations ◽  
Chronic Inflammatory Rheumatic Diseases ◽  
Juvenile Spondyloarthritis

The spondyloarthritides (or spondyloarthropathies) (SPAs) are chronic, inflammatory, rheumatic diseases of unknown origin, which share certain clinical, epidemiological, and genetic characteristics. They include ankylosing spondylitis, reactive arthritis (also known as the Reiter Syndrome), psoriatic arthritis, enteropathic spondyloarthropathy (ulcerative colitis, Crohn’s disease), undifferentiated spondyloarthritis, juvenile spondyloarthritis, and formes frustes such as acute anterior uveitis, spondyloarthritic carditis, and balanitis circinata. In the past, the SPAs were considered variants of rheumatoid arthritis, but it is now clear that they differ from the latter disease in terms of the pattern of articular and extra-articular involvement, their lack of association with seropositivity for rheumatoid factor, and their strong association with sacro-iliac joint bacino= pelvis sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint the class I human leukocyte antigen B27. sacro-iliac joint bacino= pelvis sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint Their general characteristics are axial involvement; enthesitis; peripheral arthritis involving the lower limbs, which is usually asymmetric; dactylitis; extra-articular manifestations involving the skin, eyes, bowel, and genitals. The musculoskeletal manifestations of the SPAs are due to inflammation at the level of the entheses. It is important to distinguish between the numerous clinical SPA variants based on analysis of symptoms, laboratory tests, and instrumental studies. Thanks to a greater understanding of the pathogenesis of the SPAs and the widespread availability of highly sensitive imaging modalities for their diagnosis, it is now possible to identify these diseases early and modify their course with effective therapy. This approach offers benefits to patients in terms of reduced morbidity and mortality and improved quality of life.

scholarly journals Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)

2021 ◽  
pp. 174077452110498
Author(s):  
Daniel D Murray ◽  
Abdel G Babiker ◽  
Jason V Baker ◽  
Christina E Barkauskas ◽  
Samuel M Brown ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Safety Data ◽  
Target Population ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Global Network ◽  
Specific Information ◽  
Full Potential ◽  
Design And Implementation ◽  
Multi Stage

Background/aims Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public–private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19. Five agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. Methods Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. Therapeutics for Inpatients with COVID-19 utilizes a multi-arm, multi-stage design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo, the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and Data and Safety Monitoring Board schedule was developed for the study of potential therapeutic agents with limited in-human data in hospitalized patients with COVID-19. Results As of 8 August 2021, five agents have entered the Therapeutics for Inpatients with COVID-19 master protocol and a total of 1909 participants have been randomized to one of these agents or matching placebo. There were a number of challenges faced by the study team that needed to be overcome in order to successfully implement Therapeutics for Inpatients with COVID-19 across a global network of sites. These included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff and obtaining regulatory approvals across a global network of sites. Conclusion Through a robust multi-network partnership, the Therapeutics for Inpatients with COVID-19 protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required to achieve the full potential of this approach in dealing with a global outbreak.

scholarly journals A Scoping Insight on Potential Prophylactics, Vaccines and Therapeutic Weaponry for the Ongoing Novel Coronavirus (COVID-19) Pandemic- A Comprehensive Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Priyanka Dash ◽  
Subhashree Mohapatra ◽  
Sayantan Ghosh ◽  
Bismita Nayak
Keyword(s):  
Clinical Trials ◽  
Therapeutic Strategy ◽  
Antiviral Agents ◽  
Fast Response ◽  
Etiologic Agent ◽  
Prolonged Treatment ◽  
Rdrp Activity ◽  
Open Label ◽  
Plasma Therapy ◽  
Mesenchymal Stem Cell Therapy

The emergence of highly virulent CoVs (SARS-CoV-2), the etiologic agent of novel ongoing “COVID-19” pandemics has been marked as an alarming case of pneumonia posing a large global healthcare crisis of unprecedented magnitude. Currently, the COVID-19 outbreak has fueled an international demand in the biomedical field for the mitigation of the fast-spreading illness, all through the urgent deployment of safe, effective, and rational therapeutic strategies along with epidemiological control. Confronted with such contagious respiratory distress, the global population has taken significant steps towards a more robust strategy of containment and quarantine to halt the total number of positive cases but such a strategy can only delay the spread. A substantial number of potential vaccine candidates are undergoing multiple clinical trials to combat COVID-19 disease, includes live-attenuated, inactivated, viral-vectored based, sub-unit vaccines, DNA, mRNA, peptide, adjuvant, plant, and nanoparticle-based vaccines. However, there are no licensed anti-COVID-19 drugs/therapies or vaccines that have proven to work as more effective therapeutic candidates in open-label clinical trial studies. To counteract the infection (SARS-CoV-2), many people are under prolonged treatment of many chemical drugs that inhibit the PLpro activity (Ribavirin), viral proteases (Lopinavir/Ritonavir), RdRp activity (Favipiravir, Remdesivir), viral membrane fusion (Umifenovir, Chloroquine phosphate (CQ), Hydroxychloroquine phosphate (HCQ), IL-6 overexpression (Tocilizumab, Siltuximab, Sarilumab). Mesenchymal Stem Cell therapy and Convalescent Plasma Therapy have emerged as a promising therapeutic strategy against SARS-CoV-2 virion. On the other hand, repurposing previously designed antiviral agents with tolerable safety profile and efficacy could be the only promising approach and fast response to the novel virion. In addition, research institutions and corporations have commenced the redesign of the available therapeutic strategy to manage the global crisis. Herein, we present succinct information on selected anti-COVID-19 therapeutic medications repurposed to combat SARS-CoV-2 infection. Finally, this review will provide exhaustive detail on recent prophylactic strategies and ongoing clinical trials to curb this deadly pandemic, outlining the major therapeutic areas for researchers to step in.

scholarly journals Identification and Evaluation of Potential SARS-CoV-2 Antiviral Agents Targeting mRNA Cap Guanine N7-Methyltransferase

2021 ◽  
Author(s):  
Renata Kasprzyk ◽  
Tomasz J. Spiewla ◽  
miroslaw smietanski ◽  
Sebastian Golojuch ◽  
Laura Vangeel ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Therapeutic Interventions ◽  
Binding Assays ◽  
Inhibitory Effects ◽  
Dot Blot ◽  
Rp Hplc ◽  
Structure Activity ◽  
Mrna Capping ◽  
New Ideas ◽  
A Cell

SARS-CoV-2, the cause of the currently ongoing COVID-19 pandemic, encodes its own mRNA capping machinery. Insights into this capping system may provide new ideas for therapeutic interventions and drug discovery. In this work, we employ a previously developed Py-FLINT screening approach to study the inhibitory effects of compounds against the cap guanine N7-methyltransferase enzyme, which is involved in SARS-CoV-2 mRNA capping. We screened five commercially available libraries (7039 compounds in total) to identify 83 inhibitors with IC50 < 50 μM, which were further validated using RP HPLC and dot blot assays. Novel fluorescence anisotropy binding assays were developed to examine the targeted binding site. The inhibitor structures were analyzed for structure-activity relationships in order to define common structural patterns. Finally, the most potent inhibitors were tested for antiviral activity on SARS-CoV-2 in a cell based assay<br>

Abstract 64: A Tale of Seven EMS Systems: An Impedance Threshold Device and Improved CPR Techniques Double Survival Rates After Out-of-Hospital Cardiac Arrest

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tom P Aufderheide ◽  
Marvin Birnbaum ◽  
Charles Lick ◽  
Brent Myers ◽  
Laurie Romig ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Hospital Discharge ◽  
Life Support ◽  
Survival Rates ◽  
Heart Association ◽  
Outcome Data ◽  
Therapeutic Interventions ◽  
Threshold Device ◽  
Hospital Cardiac Arrest ◽  
Impedance Threshold Device

Introduction: Maximizing outcomes after cardiac arrest depends on optimizing a sequence of interventions from collapse to hospital discharge. The 2005 American Heart Association (AHA) Guidelines recommended many new interventions during CPR (‘New CPR’) including use of an Impedance Threshold Device (ITD). Hypothesis: The combination of the ITD and ‘New CPR’ will increase return of spontaneous circulation (ROSC) and hospital discharge (HD) rates in patients with an out-of-hospital cardiac arrest. Methods: Quality assurance data were pooled from 7 emergency medical services (EMS) systems (Anoka Co., MN; Harris Co., TX; Madison, WI; Milwaukee, WI; Omaha, NE; Pinellas Co., FL; and Wake Co., NC) where the ITD (ResQPOD®, Advanced Circulatory Systems; Minneapolis, MN) was deployed for >3 months. Historical or concurrent control data were used for comparison. The EMS systems simultaneously implemented ‘New CPR’ including compression/ventilation strategies to provide more compressions/min and continuous compressions during Advanced Life Support. All sites stressed the importance of full chest wall recoil. The sites have a combined population of ~ 3.2 M. ROSC data were available from all sites; HD data were available as of June 2007 from 5 sites (MN, TX, Milwaukee, NE, NC). Results: A total of 893 patients treated with ‘New CPR’ + ITD were compared with 1424 control patients. The average age of both study populations was 64 years; 65% were male. Comparison of the ITD vs controls (all patients) for ROSC and HD [Odds ratios (OR), (95% confidence intervals), and Fisher’s Exact Test] were: 37.9% vs 33.8% [1.2, (1.02, 1.40), p=0.022] and 15.7% vs 7.9% [2.2, (1.53, 3.07), p<0.001], respectively. Patients with ventricular fibrillation had the best outcomes in both groups. Neurological outcome data are pending. Therapeutic hypothermia was used in some patients (MN, NC) after ROSC. Conclusion: Adoption of the ITD + ‘New CPR’ resulted in only a >10% increase in ROSC rates but a doubling of hospital discharge rates, from 7.9% to 15.7%, (p<0.001). These data represent a currently optimized sequence of therapeutic interventions during the performance of CPR for patients in cardiac arrest and support the widespread use of the 2005 AHA CPR Guidelines including use of the ITD.

scholarly journals Surveillance of Human Rotavirus in Wuhan, China (2011–2019): Predominance of G9P[8] and Emergence of G12

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 810
Author(s):  
Xuan Zhou ◽  
Yuan-Hong Wang ◽  
Bei-Bei Pang ◽  
Nan Chen ◽  
Nobumichi Kobayashi
Keyword(s):  
Etiologic Agent ◽  
Genetic Characteristics ◽  
Predominant Genotype ◽  
Rotavirus A ◽  
Epidemic Season ◽  
Human Rotavirus ◽  
Stool Specimens ◽  
Virus Strains ◽  
Nsp3 Gene ◽  
Infants And Young Children

Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. To learn the shift of genotypes and genetic characteristics of Rotavirus A (RVA) causing diarrhea in children and adults, a hospital-based surveillance of rotavirus was conducted in Wuhan, China from June 2011 through May 2019, and representative virus strains were phylogenetically analyzed. Among a total of 6733 stool specimens collected from both children and adults with acute gastroenteritis, RVA was detected in 25.5% (1125/4409) and 12.3% (285/2324) of specimens, respectively. G9P[8] was the most common genotype (74.5%), followed by G1P[8] (8.7%), G2P[4] (8.4%), and G3P[8] (7.3%), with G9P[8] increasing rapidly during the study period. The predominant genotype shifted from G1P[8] to G9P[8] in 2012–2013 epidemic season. G12P[6] strain RVA/Human-wt/CHN/Z2761/2019/G12P[6] was detected in April 2019 and assigned to G12-P[6]-I1-R1-C1-M1-A1-N1-T2-E1-H1 genotypes. Phylogenetic analysis revealed that VP7, VP4, VP6, VP3, NSP1, NSP2, and NSP5 genes of Z2761 clustered closely with those of Korean G12P[6] strain CAU_214, showing high nucleotide identities (98.0–98.8%). The NSP3 gene of Z2761 was closely related to those of G2P[4] and G12P[6] rotaviruses in Asia. All the eleven gene segments of Z2761 kept distance from those of cocirculating G9P[8], G1P[8], and G3P[8] strains detected in Wuhan during this study period. This is the first identification of G12 rotavirus in China. It is deduced that Z2761 is a reassortant having DS-1-like NSP3 gene in the background of G12P[6] rotavirus genetically close to CAU_214.

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