scholarly journals A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants

2021 ◽  
Vol 10 (15) ◽  
pp. 3276
Author(s):  
Philippe Colson ◽  
Christian A. Devaux ◽  
Jean-Christophe Lagier ◽  
Philippe Gautret ◽  
Didier Raoult
Keyword(s):  
Neutralizing Antibodies ◽  
Selective Sweep ◽  
Immune Escape ◽  
High Rate ◽  
Immunocompromised Patients ◽  
Plasma Therapy ◽  
Rapid Changes ◽  
Experimental Therapies ◽  
The Uk

Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or vaccine immunization. The usual coronavirus mutation rate through genetic drift alone cannot account for such rapid changes. Recent reports of the occurrence of such mutations in immunocompromised patients who received remdesivir and/or convalescent plasma or monoclonal antibodies to treat prolonged SARS-CoV-2 infections led us to hypothesize that experimental therapies that fail to cure the patients from COVID-19 could favor the emergence of immune escape SARS-CoV-2 variants. We review here the data that support this hypothesis and urge physicians and clinical trial promoters to systematically monitor viral mutations by whole-genome sequencing for patients who are administered these treatments.

scholarly journals Rapid Changes in the Genetic Composition of Stagonosporopsis tanaceti Population in Australian Pyrethrum Fields

2015 ◽  
Vol 105 (3) ◽  
pp. 358-369 ◽  
Author(s):  
Niloofar Vaghefi ◽  
Frank S. Hay ◽  
Peter K. Ades ◽  
Sarah J. Pethybridge ◽  
Rebecca Ford ◽  
...  
Keyword(s):  
Selective Sweep ◽  
Management Strategies ◽  
Rapid Change ◽  
Genetic Composition ◽  
Significant Linkage Disequilibrium ◽  
Long Distance ◽  
Ray Blight ◽  
Rapid Changes ◽  
Significant Linkage

A novel set of microsatellite markers were developed and employed for geographical and temporal population analyses of Stagonosporopsis tanaceti, the cause of ray blight of pyrethrum in Australia. Genotyping of 407 isolates, using 13 markers, suggested an asexual mode of reproduction with significant linkage disequilibrium and high levels of clonality. Low geographical differentiation and widespread distribution of a few multilocus genotypes (MLGs), in the absence of airborne ascospores, suggested the role of human-mediated movement of seed as a major means of long-distance pathogen dispersal. The genetic composition of S. tanaceti was stable for a decade then changed rapidly in only 2 years. Bayesian clustering analyses and minimum spanning networks determined only two major clonal lineages in and prior to 2010. However, in 2012, a previously unobserved cluster of MLGs was detected, which significantly increased in frequency and displaced the historically dominant MLGs by 2013. This rapid change in the genetic composition of S. tanaceti could indicate a second introduction then a selective sweep, or strong selection pressures from recently introduced fungicides or pyrethrum varieties. These results may have serious implications for durability of management strategies for this disease.

Monoclonal antibodies reveal the potential of the tetragnathid spider Pachygnatha degeeri (Araneae: Tetragnathidae) as an aphid predator

2005 ◽  
Vol 95 (2) ◽  
pp. 161-167 ◽  
Author(s):  
J.D. Harwood ◽  
K.D. Sunderland ◽  
W.O.C. Symondson
Keyword(s):  
Monoclonal Antibodies ◽  
Integrated Approach ◽  
High Rate ◽  
Generalist Predators ◽  
Large Numbers ◽  
Aphid Predators ◽  
Predator Complex ◽  
The Uk ◽  
Establishment Phase

AbstractThe drive towards a more sustainable and integrated approach to pest management has engendered a renewed interest in conservation biological control, the role of natural enemy communities and their interactions with prey. Monoclonal antibodies have provided significant advances in enhancing our knowledge of trophic interactions and can be employed to help quantify predation on target species. The tetragnathid spider Pachygnatha degeeri Sundevall was collected from fields of winter wheat in the UK and assayed by ELISA for aphid proteins. It was demonstrated that this spider did not simply consume greater quantities of aphids because it was bigger. In addition, P. degeeri contained significantly greater concentrations of aphid in their guts than other spiders, showing that aphids comprised a greater proportion of their diet. Although P. degeeri constituted only 6% of the spider population numerically, females and males respectively contained 16% and 37% of total aphid proteins within all spiders screened, significantly more than their density would predict. These spiders also preyed upon aphids at a disproportionately high rate in June, during the aphid establishment phase, theoretically the best time for limiting growth in the aphid population. Although less abundant than other generalist predators, the capability of these hunting spiders to consume large numbers of aphids highlights them as a more significant component of the predator complex than had previously been realized. Limitation of aphid numbers early in the year by generalist predators provides more time for the specialist aphid predators and parasitoids to move in.

scholarly journals The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 734
Author(s):  
Mohamed Moubarak ◽  
Keneth Iceland Kasozi ◽  
Helal F. Hetta ◽  
Hazem M. Shaheen ◽  
Abdur Rauf ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Neutralizing Antibodies ◽  
Survival Rates ◽  
H1n1 Influenza ◽  
Host Responses ◽  
Novel Therapies ◽  
Clotting Factors ◽  
Plasma Therapy ◽  
Community Transmission

Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1β, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19.

The financial action taskforce and money laundering: critical analysis of the Panama papers and the role of the United Kingdom

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Aisha Hassan Al-Emadi
Keyword(s):  
Money Laundering ◽  
Design Methodology ◽  
Task Force ◽  
Content Type ◽  
The United Kingdom ◽  
Rapid Changes ◽  
Financial Action Task ◽  
The Uk ◽  
Desk Review

Purpose This paper aims to study the effectiveness of the implementation of the Financial Action Task Force (FATF) recommendations in the UK in an attempt to combat the laundering of proceeds of corruption. Design/methodology/approach A desk review of secondary resources was conducted to analyze available literature to examine the research topic. Findings The leakage of 11.5 million documents, known as the Panama papers, has revealed that the UK functioned as a safe haven for illicit and corrupt money. In an attempt to address this, the country called for a public registry of beneficial owners to disclose the identities of the owners of the incorporated corporations and to extend them to individuals abroad holding UK property. The FATF report recognizes the UK’s far-reaching regulation. Despite the measures taken, UK still faces serious risks with regard to the laundering of criminal proceeds, which demonstrates that technical compliance with FATF rules is not enough to effectively curb money laundering. Originality/value This study suggests that FATF rules’ effectiveness in identifying instances of laundering the proceeds of corruption is limited because of the deeply rooted system vulnerabilities and the rapid changes in money laundering trends.

scholarly journals Semen-Derived Exosomes Mediate Immune Escape and Transmission of Reticuloendotheliosis Virus

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Su ◽  
Yawen Zhang ◽  
Zhizhong Cui ◽  
Shuang Chang ◽  
Peng Zhao
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Virus Transmission ◽  
Reticuloendotheliosis Virus ◽  
Viral Shedding ◽  
Reverse Transcription Pcr ◽  
Viral Genomic Rna

Reticuloendotheliosis virus (REV) causes immune-suppression disease in poultry, leading to a significant economic burden worldwide. Recent evidence demonstrated that the REV can enter the semen and then induce artificial insemination, but how the virus gets into semen was little known. Accumulating studies indicated that exosomes serve as vehicles for virus transmission, but the role of exosomes in viral shedding through the semen remains unclear. In this study, exosomes purified from the REV-positive semen were shown with reverse transcription-PCR and mass spectrometry to contain viral genomic RNA and viral proteins, which could also establish productive infections both in vivo and in vitro and escape from the REV-specific neutralizing antibodies. More importantly, compared with the infection caused by free virions, the exosome is more efficient for the virus to ensure effective infection and replication, which can also help the REV compromise the efficacy of the host immune response. In summary, this study demonstrated that semen-derived exosomes can medicate the transmission and immune escape of REV, implicating a novel mechanism for REV entering the semen and leading to vertical transmission.

scholarly journals Nature and dimensions of the cytokine storm and its attenuation by convalescent plasma in severe COVID-19

2020 ◽  
Author(s):  
Purbita Bandopadhyay ◽  
Ranit D’Rozario ◽  
Abhishake Lahiri ◽  
Jafar Sarif ◽  
Yogiraj Ray ◽  
...  
Keyword(s):  
Randomized Control Trial ◽  
Neutralizing Antibodies ◽  
Distress Syndrome ◽  
Neutralizing Antibody ◽  
Cytokine Storm ◽  
Plasma Therapy ◽  
Mild Disease ◽  
Chemotactic Protein ◽  
Randomized Control

SummaryTo characterize key components and dynamics of the cytokine storm associated with severe COVID-19 disease, we assessed abundance and correlative expression of a panel of forty eight cytokines in patients suffering from acute respiratory distress syndrome (ARDS), as compared to patients with mild disease. Then in a randomized control trial on convalescent plasma therapy (CPT) in COVID-19 ARDS, we analyzed the immediate effects of CPT on the dynamics of the cytokine storm as a correlate for the level of hypoxia experienced by the patients. Plasma level of monocyte chemotactic protein 3 was found to be a key correlate for clinical improvement, irrespective of therapy received. We also identified a hitherto unappreciated anti-inflammatory role of CPT independent of its neutralizing antibody content. Neutralizing antibodies as well as reductions in circulating interleukin-6 and interferon gamma induced protein 10, both contributed to marked immediate reductions in hypoxia in severe COVID-19 patients receiving CPT.Abstract Figure

scholarly journals Genomic Evidence of a Sars-Cov-2 Reinfection Case With E484K Spike Mutation in Brazil

2021 ◽  
Author(s):  
Carolina Kymie Vasques Nonaka ◽  
Marília Miranda Franco ◽  
Tiago Gräf ◽  
Ana Verena Almeida Mendes ◽  
Renato Santana de Aguiar ◽  
...  
Keyword(s):  
South Africa ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Viral Evolution ◽  
First Episode ◽  
Receptor Binding Domain ◽  
First Case ◽  
Potential Impact ◽  
The Uk

To date, uncertainty remains about how long the protective immune responses against SARS-CoV-2 persists and the first reports of suspected reinfection began to be described in recovered patients months after the first episode. Viral evolution may favor reinfections, and the recently described spike mutations, particularly in the receptor binding domain (RBD) in SARS-CoV-2 lineages circulating in the UK, South Africa, and most recently in Brazil, have raised concern on their potential impact in infectivity and immune escape. We report the first case of reinfection from genetically distinct SARS-CoV-2 lineage presenting the E484K spike mutation in Brazil, a variant associated with escape from neutralizing antibodies.

scholarly journals Altered Local Interactions and Long-Range Communications in UK Variant (B.1.1.7) Spike Glycoprotein

2021 ◽  
Vol 22 (11) ◽  
pp. 5464
Author(s):  
Stefano Borocci ◽  
Carmen Cerchia ◽  
Alessandro Grottesi ◽  
Nico Sanna ◽  
Ingrid Guarnetti Prandi ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Structural Information ◽  
Conformational Transitions ◽  
Structural Basis ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Dynamics Simulations ◽  
The Uk ◽  
The Impact

The COVID-19 pandemic is caused by SARS-CoV-2. Currently, most of the research efforts towards the development of vaccines and antibodies against SARS-CoV-2 were mainly focused on the spike (S) protein, which mediates virus entry into the host cell by binding to ACE2. As the virus SARS-CoV-2 continues to spread globally, variants have emerged, characterized by multiple mutations of the S glycoprotein. Herein, we employed microsecond-long molecular dynamics simulations to study the impact of the mutations of the S glycoprotein in SARS-CoV-2 Variant of Concern 202012/01 (B.1.1.7), termed the “UK variant”, in comparison with the wild type, with the aim to decipher the structural basis of the reported increased infectivity and virulence. The simulations provided insights on the different dynamics of UK and wild-type S glycoprotein, regarding in particular the Receptor Binding Domain (RBD). In addition, we investigated the role of glycans in modulating the conformational transitions of the RBD. The overall results showed that the UK mutant experiences higher flexibility in the RBD with respect to wild type; this behavior might be correlated with the increased transmission reported for this variant. Our work also adds useful structural information on antigenic “hotspots” and epitopes targeted by neutralizing antibodies.

Management of deradicalisation in the UK: reflections of a clinical psychologist

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Feryad A. Hussain
Keyword(s):  
Clinical Psychologist ◽  
Healthcare Team ◽  
Psychosocial Issues ◽  
Muslim Community ◽  
Home Office ◽  
Terrorist Groups ◽  
Violent Action ◽  
Clinical Counselling ◽  
The Uk

Radicalisation to violent action is not just a problem in foreign lands. Research has identified numerous politico–psychosocial factors to explain why young people from the UK are now joining terrorist groups such as ISIS. Our understanding has been expanded by the accounts of “returnees” who have subsequently either self-deradicalised or joined a government deradicalisation programme in the role of an Intervention Provider (IP). These individuals are now key to the deradicalisation programme. This article presents the reflections of a clinical psychologist who worked within a social healthcare team managing psychosocial issues related to radicalisation, in conjunction with an allocated IP. The project involved individuals from the Muslim community and, as such, issues discussed are specific to this group. It is acknowledged that the process in general is universally applicable to all groups though specifics may vary (under Trust agreement, details may not be discussed). This article also aims to share basic information on the current Home Office deradicalisation programme and raises questions about the current intervention. It also offers reflections on how the work of IPs may be facilitated and supported by clinical/counselling psychologists and psychotherapists.

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