scholarly journals The natural stilbenoid (–)-hopeaphenol inhibits cellular entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7 and B.1.351 variants

2021 ◽  
Author(s):  
Ian Tietjen ◽  
Joel Cassel ◽  
Emery T. Register ◽  
Xiang Yang Zhou ◽  
Troy E. Messick ◽  
...  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Receptor Binding ◽  
Viral Entry ◽  
Cytopathic Effect ◽  
Selective Inhibitors ◽  
The United Kingdom ◽  
Pure Compounds ◽  
The Usa

AbstractAntivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host ACE2 receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (–)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry. For example, (–)-hopeaphenol disrupted RBD/ACE2 binding with a 50% inhibitory concentration (IC50) of 0.11 μM in contrast to an IC50 of 28.3 μM against the unrelated host ligand/receptor binding pair PD-1/PD-L1 (selectivity index = 257.3). When assessed against the USA-WA1/2020 variant, (–)-hopeaphenol also inhibited entry of a VSVΔG-GFP reporter pseudovirus expressing SARS-CoV-2 spike into ACE2-expressing Vero-E6 cells and in vitro replication of infectious virus in cytopathic effect assays (IC50 = 10.2 μM) without cytotoxicity. Notably, (–)- hopeaphenol also inhibited two emerging variants of concern originating from the United Kingdom (B.1.1.7) and South Africa (B.1.351) in both cytopathic effect and spike-containing pseudovirus assays with similar (B.1.1.7) or improved (B.1.351) efficacies over the USA- WA1/2020 variant. These results identify (–)-hopeaphenol and related stilbenoid analogues as potent and selective inhibitors of viral entry across multiple SARS-CoV-2 variants including those with increased infectivity and/or reduced susceptibility to existing vaccines.ImportanceSARS-CoV-2 antivirals are needed to supplement existing vaccine efforts and target emerging viral variants with increased infectivity or reduced susceptibility to existing vaccines. Here we show that (–)-hopeaphenol, a naturally-occurring stilbenoid compound, in addition to its analogues vatalbinoside A and vaticanol B, inhibit SARS-CoV-2 by blocking the interaction of the viral spike protein with the cellular ACE2 entry receptor. Importantly, in addition to inhibiting the early USA-WA1/2020 SARS-CoV-2 variant, hopeaphenol also inhibits emerging variants of concern including B.1.1.7 (“United Kingdom variant”) and B.1.351 (“South Africa variant”), with improved efficacy against B.1.351. (–)-Hopeaphenol therefore represents a new antiviral lead against infection from multiple SARS-CoV-2 variants.

scholarly journals The natural stilbenoid (–)-hopeaphenol inhibits cellular entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7 and B.1.351 variants

2021 ◽  
Author(s):  
Ian Tietjen ◽  
Joel Cassel ◽  
Emery T. Register ◽  
Xiang Yang Zhou ◽  
Troy E. Messick ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Viral Entry ◽  
Inhibitory Concentration ◽  
Cell Entry ◽  
Yield Reduction ◽  
Selective Inhibitors ◽  
Gfp Reporter ◽  
Pure Compounds ◽  
The Usa

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host ACE2 receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (–)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry. For example, (–)-hopeaphenol disrupted RBD/ACE2 binding with a 50% inhibitory concentration (IC50) of 0.11 μM in contrast to an IC50 of 28.3 μM against the unrelated host ligand/receptor binding pair PD-1/PD-L1 (selectivity index = 257.3). When assessed against the USA-WA1/2020 variant, (–)-hopeaphenol also inhibited entry of a VSVΔG-GFP reporter pseudovirus expressing SARS-CoV-2 spike into ACE2-expressing Vero-E6 cells and in vitro replication of infectious virus in cytopathic effect and yield reduction assays (50% effective concentrations (EC50s) = 10.2 – 23.4 μM) without cytotoxicity and approaching the activities of the control antiviral remdesivir (EC50s = 1.0 – 7.3 μM). Notably, (–)-hopeaphenol also inhibited two emerging variants of concern including B.1.1.7/”Alpha” and B.1.351/”Beta” in both viral and spike-containing pseudovirus assays with similar or improved activities over the USA-WA1/2020 variant. These results identify (–)-hopeaphenol and related stilbenoid analogues as potent and selective inhibitors of viral entry across multiple SARS-CoV-2 variants of concern.

scholarly journals RIC in COVID-19—a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19

2021 ◽  
Author(s):  
Sean M. Davidson ◽  
Kishal Lukhna ◽  
Diana A. Gorog ◽  
Alan D. Salama ◽  
Alejandro Rosell Castillo ◽  
...  
Keyword(s):  
South Africa ◽  
Clinical Trial ◽  
United Kingdom ◽  
Inflammatory Cytokines ◽  
In Vitro Cytotoxicity ◽  
Cytokine Storm ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
The United Kingdom

Abstract Purpose Coronavirus disease 19 (COVID-19) has, to date, been diagnosed in over 130 million persons worldwide and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several variants of concern have emerged including those in the United Kingdom, South Africa, and Brazil. SARS-CoV-2 can cause a dysregulated inflammatory response known as a cytokine storm, which can progress rapidly to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Suppressing these cytokine elevations may be key to improving outcomes. Remote ischemic conditioning (RIC) is a simple, non-invasive procedure whereby a blood pressure cuff is inflated and deflated on the upper arm for several cycles. “RIC in COVID-19” is a pilot, multi-center, randomized clinical trial, designed to ascertain whether RIC suppresses inflammatory cytokine production. Methods A minimum of 55 adult patients with diagnosed COVID-19, but not of critical status, will be enrolled from centers in the United Kingdom, Brazil, and South Africa. RIC will be administered daily for up to 15 days. The primary outcome is the level of inflammatory cytokines that are involved in the cytokine storm that can occur following SARS-CoV-2 infection. The secondary endpoint is the time between admission and until intensive care admission or death. The in vitro cytotoxicity of patient blood will also be assessed using primary human cardiac endothelial cells. Conclusions The results of this pilot study will provide initial evidence on the ability of RIC to suppress the production of inflammatory cytokines in the setting of COVID-19. Trial Registration NCT04699227, registered January 7th, 2021.

Solving the Problems of Finding Law on the Web: World Law and DIAL

2001 ◽  
Vol 29 (2) ◽  
pp. 383-419 ◽  
Author(s):  
Graham Greenleaf
Keyword(s):  
South Africa ◽  
Developing Countries ◽  
United Kingdom ◽  
Latin American ◽  
Full Text ◽  
The United Kingdom ◽  
The Usa ◽  
Almost All ◽  
Latin American Countries ◽  
The Web

Despite its recent development, the Web already contains an astonishing variety of legal materials from dozens of countries. Significant collections of legislation are already available on the Web from over 50 countries. The full text is available on the Web of all legislation from almost all the jurisdictions of the USA, Canada, Australasia, many Latin American countries and some European countries (such as Norway and Germany), and extensive collections from many other European counties (such as the United Kingdom, France, Spain, Portugal). Substantial collections of legislation are available from many developing countries, including India, Turkey, Kazakhstan, South Africa, Vietnam, Zambia, China, Mexico and Israel.

scholarly journals Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera

2021 ◽  
Author(s):  
Pei-Yong Shi ◽  
Xuping Xie ◽  
Jing Zou ◽  
Camila Fontes-Garfias ◽  
Hongjie Xia ◽  
...  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Binding Site ◽  
Receptor Binding ◽  
Cell Entry ◽  
Receptor Binding Site ◽  
Viral Receptor ◽  
The United Kingdom ◽  
Human Sera

Abstract Rapidly spreading variants of SARS-CoV-2 that have arisen in the United Kingdom and South Africa share the spike N501Y substitution, which is of particular concern because it is located in the viral receptor binding site for cell entry and increases binding to the receptor. We generated isogenic N501 and Y501 SARS-CoV-2. Twenty human sera from the mRNA-based vaccine BNT162b2 trial exhibited equivalent neutralizing titers to the N501 and Y501 viruses.

scholarly journals Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera

2021 ◽  
Author(s):  
Xuping Xie ◽  
Jing Zou ◽  
Camila R. Fontes-Garfias ◽  
Hongjie Xia ◽  
Kena A. Swanson ◽  
...  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Cell Entry ◽  
Converting Enzyme ◽  
Receptor Binding Site ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
The United Kingdom

Rapidly spreading variants of SARS-CoV-2 that have arisen in the United Kingdom and South Africa share the spike N501Y substitution, which is of particular concern because it is located in the viral receptor binding site for cell entry and increases binding to the receptor (angiotensin converting enzyme 2). We generated isogenic N501 and Y501 SARS-CoV-2. Sera of 20 participants in a previously reported trial of the mRNA-based COVID-19 vaccine BNT162b2 had equivalent neutralizing titers to the N501 and Y501 viruses.

scholarly journals Plausible Transition of Covid-19 from Pandemic to an Endemic State: Impact of Variant UK Strain, b 7.1.1, on the Spread of Covid-19 in the Population

2021 ◽  
Vol 4 (2) ◽  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Causative Agent ◽  
Original Form ◽  
The United Kingdom ◽  
Recent Emergence ◽  
The World ◽  
The Usa ◽  
Disease Spreading ◽  
Endemic State

Covid-19 is a contagious disease spreading without showing any signs of abatement across the world. Presently, sars-cov-2, the causative agent of covid-19, is giving a fresh threatening signs to renew its devastation as several new mutated strains have been detected in United Kingdom, south africa, brazil & the usa; the first variant being detected in the united kingdom (b 7.1.1). Here we have shown that there was a gradual waning of active cases of covid-19 (strain originated in wuhan, china) across the nation after implementation of complete lockdown; this demonstrated that covid-19 had lost its sheen and the covid-19 pandemic was nearing an end. However, the recent emergence of the mutated forms of sars-cov-2 in different countries including India, appears to be more contagious and virulent than the original form. This property of the variant strain could affect the ongoing pandemic. The implication of all the data obtained from the old and the new UK variant, b7.1.1, in context of pandemic has been discussed in this article.

scholarly journals A cross-sectional survey assessing the influence of theoretically informed behavioural factors on hand hygiene across seven countries during the COVID-19 pandemic

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
K. A. Schmidtke ◽  
K. G. Drinkwater
Keyword(s):  
South Africa ◽  
Saudi Arabia ◽  
United Kingdom ◽  
Hand Hygiene ◽  
Behaviour Change ◽  
Surface Cleaning ◽  
Behaviour Change Techniques ◽  
Cross Sectional ◽  
Surface Areas ◽  
The United Kingdom

Abstract Background Human hygiene behaviours influence the transmission of infectious diseases. Changing maladaptive hygiene habits has the potential to improve public health. Parents and teachers can play an important role in disinfecting surface areas and in helping children develop healthful handwashing habits. The current study aims to inform a future intervention that will help parents and teachers take up this role using a theoretically and empirically informed behaviour change model called the Capabilities-Opportunities-Motivations-Behaviour (COM-B) model. Methods A cross-sectional online survey was designed to measure participants’ capabilities, opportunities, and motivations to [1] increase their children’s handwashing with soap and [2] increase their cleaning of surface areas. Additional items captured how often participants believed their children washed their hands. The final survey was administered early in the coronavirus pandemic (May and June 2020) to 3975 participants from Australia, China, India, Indonesia, Saudi Arabia, South Africa, and the United Kingdom. Participants self-identified as mums, dads, or teachers of children 5 to 10 years old. ANOVAs analyses were used to compare participant capabilities, opportunities, and motivations across countries for handwashing and surface disinfecting. Multiple regressions analyses were conducted for each country to assess the predictive relationship between the COM-B components and children’s handwashing. Results The ANOVA analyses revealed that India had the lowest levels of capability, opportunity, and motivation, for both hand hygiene and surface cleaning. The regression analyses revealed that for Australia, Indonesia, and South Africa, the capability component was the only significant predictor of children’s handwashing. For India, capability and opportunity were significant. For the United Kingdom, capability and motivation were significant. Lastly, for Saudi Arabia all components were significant. Conclusions The discussion explores how the Behaviour Change Wheel methodology could be used to guide further intervention development with community stakeholders in each country. Of the countries assessed, India offers the greatest room for improvement, and behaviour change techniques that influence people’s capability and opportunities should be prioritised there.

The global effectiveness of fact-checking: Evidence from simultaneous experiments in Argentina, Nigeria, South Africa, and the United Kingdom

2021 ◽  
Vol 118 (37) ◽  
pp. e2104235118 ◽  
Author(s):  
Ethan Porter ◽  
Thomas J. Wood
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Health Outcomes ◽  
False Beliefs ◽  
Point Scale ◽  
Analytic Procedure ◽  
The United Kingdom ◽  
Fact Checking ◽  
Checking Experiments

The spread of misinformation is a global phenomenon, with implications for elections, state-sanctioned violence, and health outcomes. Yet, even though scholars have investigated the capacity of fact-checking to reduce belief in misinformation, little evidence exists on the global effectiveness of this approach. We describe fact-checking experiments conducted simultaneously in Argentina, Nigeria, South Africa, and the United Kingdom, in which we studied whether fact-checking can durably reduce belief in misinformation. In total, we evaluated 22 fact-checks, including two that were tested in all four countries. Fact-checking reduced belief in misinformation, with most effects still apparent more than 2 wk later. A meta-analytic procedure indicates that fact-checks reduced belief in misinformation by at least 0.59 points on a 5-point scale. Exposure to misinformation, however, only increased false beliefs by less than 0.07 points on the same scale. Across continents, fact-checks reduce belief in misinformation, often durably so.

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