scholarly journals Repurposing of FDA-Approved Toremifene to Treat COVID-19 by Blocking the Spike Glycoprotein and NSP14 of SARS-CoV-2

2020 ◽  
Author(s):  
William R. Martin ◽  
Feixiong Cheng
Keyword(s):  
The United States ◽  
Dynamics Simulation ◽  
Heptad Repeat ◽  
Drug Candidate ◽  
Structural Protein ◽  
Spike Glycoprotein ◽  
Receptor Modulator ◽  
Global Pandemic ◽  
Structural Mechanisms ◽  
Binding Affinity Calculations

The global pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to the death of more than 350,000 worldwide and over 100,000 in the United States alone. However, there are currently no proven effective pharmacotherapies for COVID-19. Here, we combine homology modeling, molecular docking, molecular dynamics simulation, and binding affinity calculations to determine potential targets for toremifene, a selective estrogen receptor modulator which we have previously identified as a SARS-CoV-2 inhibitor. Our results indicate the possibility of inhibition of the spike glycoprotein by toremifene, responsible for aiding in fusion of the viral membrane with the cell membrane, via a perturbation to the fusion core. An interaction between the dimethylamine end of toremifene and residues Q954 and N955 in heptad repeat 1 (HR1) perturbs the structure, causing a shift from what is normally a long, helical region to short helices connected by unstructured regions. Additionally, we found a strong interaction between toremifene and the methyltransferase non-structural protein (NSP) 14, which could be inhibitory to viral replication via its active site. These results suggest potential structural mechanisms for toremifene by blocking the spike protein and NSP14 of SARS-CoV-2, offering a drug candidate for COVID-19.

scholarly journals Repurposing of FDA-Approved Toremifene to Treat COVID-19 by Blocking the Spike Glycoprotein and NSP14 of SARS-CoV-2

2020 ◽  
Author(s):  
William R. Martin ◽  
Feixiong Cheng
Keyword(s):  
The United States ◽  
Dynamics Simulation ◽  
Heptad Repeat ◽  
Drug Candidate ◽  
Structural Protein ◽  
Spike Glycoprotein ◽  
Receptor Modulator ◽  
Global Pandemic ◽  
Structural Mechanisms ◽  
Binding Affinity Calculations

The global pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to the death of more than 350,000 worldwide and over 100,000 in the United States alone. However, there are currently no proven effective pharmacotherapies for COVID-19. Here, we combine homology modeling, molecular docking, molecular dynamics simulation, and binding affinity calculations to determine potential targets for toremifene, a selective estrogen receptor modulator which we have previously identified as a SARS-CoV-2 inhibitor. Our results indicate the possibility of inhibition of the spike glycoprotein by toremifene, responsible for aiding in fusion of the viral membrane with the cell membrane, via a perturbation to the fusion core. An interaction between the dimethylamine end of toremifene and residues Q954 and N955 in heptad repeat 1 (HR1) perturbs the structure, causing a shift from what is normally a long, helical region to short helices connected by unstructured regions. Additionally, we found a strong interaction between toremifene and the methyltransferase non-structural protein (NSP) 14, which could be inhibitory to viral replication via its active site. These results suggest potential structural mechanisms for toremifene by blocking the spike protein and NSP14 of SARS-CoV-2, offering a drug candidate for COVID-19.

Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity and Pathogenesis?

2020 ◽  
Author(s):  
Angelo Spinello ◽  
Andrea Saltalamacchia ◽  
Alessandra Magistrato
Keyword(s):  
Health Economic ◽  
Global Health ◽  
Receptor Binding ◽  
Binding Motif ◽  
Spike Glycoprotein ◽  
High Affinity ◽  
Global Pandemic ◽  
Medical Countermeasures ◽  
High Infectivity ◽  
Human Receptor

<p>The latest outbreak of a new pathogenic coronavirus (SARS-CoV-2) is provoking a global health, economic and societal crisis. All-atom simulations enabled us to uncover the key molecular traits underlying the high affinity of SARS-CoV-2 spike glycoprotein towards its human receptor, providing a rationale to its high infectivity. Harnessing this knowledge can boost developing effective medical countermeasures to fight the current global pandemic.</p>

Unique nCoV-2019 (COVID 19) spike glycoprotein processing by host protease: Analysis and Implication on infection

2020 ◽  
Vol 17 ◽  
Author(s):  
Ajoy Basak ◽  
Sarmistha Basak
Keyword(s):  
World Health ◽  
Spike Glycoprotein ◽  
Binding Domains ◽  
Corona Virus ◽  
Global Pandemic ◽  
High Infection ◽  
Crucial Information ◽  
Glycoprotein Processing ◽  
Health Organization ◽  
Host Reservoir

: The current global pandemic outbreak of a novel type of corona virus termed by World Health Organization as COVID-19 became an grave concern and worry to human health and world economy. Intense research efforts are now underway worldwide to combat and prevent the spread of this deadly disease. This zoonotic virus, a native to bat population is most likely transmitted to human via a host reservoir. Due to its close similarity to previously known SARS CoV (Severe Acute Respiratory Syndrome Corona Virus) of 2002 and related MERS CoV (Middle East Respiratory Syndrome Corona Virus) of 2012, it is also known as SARS CoV2. But unlike them it is far too infectious, virulent and lethal. Among its various proteins, the surface spike glycoprotein “S” has drawn significant attention because of its implication in viral recognition and host-virus fusion process. A detail comparative analysis of “S” proteins of SARS CoV (now called SARS CoV1), SARS CoV2 (COVID-19) and MERS CoV based on structure, sequence alignment, host cleavage sites, receptor binding domains, potential glycosylation and Cys-disulphide bridge locations has been performed. It revealed some key features and variations that may elucidate the high infection and virulence character of COVID-19. Moreover this crucial information may become useful in our quest for COVID-19 therapeutics and vaccines.

scholarly journals Influenza vaccination and the risk of COVID-19 infection and severe illness in older adults in the United States

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kelly Huang ◽  
Shu-Wen Lin ◽  
Wang-Huei Sheng ◽  
Chi-Chuan Wang
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
The United States ◽  
Cross Sectional Study ◽  
Severe Illness ◽  
Cross Sectional ◽  
Global Pandemic ◽  
Study Population ◽  
Health Database

AbstractThe coronavirus disease of 2019 (COVID-19) has caused a global pandemic and led to nearly three million deaths globally. As of April 2021, there are still many countries that do not have COVID-19 vaccines. Before the COVID-19 vaccines were developed, some evidence suggested that an influenza vaccine may stimulate nonspecific immune responses that reduce the risk of COVID-19 infection or the severity of COVID-19 illness after infection. This study evaluated the association between influenza vaccination and the risk of COVID-19 infection. We conducted a retrospective cross-sectional study with data from July 1, 2019, to June 30, 2020 with the Claims data from Symphony Health database. The study population was adults age 65 years old or older who received influenza vaccination between September 1 and December 31 of 2019. The main outcomes and measures were odds of COVID-19 infection and severe COVID-19 illness after January 15, 2020. We found the adjusted odds ratio (aOR) of COVID-19 infection risk between the influenza-vaccination group and no-influenza-vaccination group was 0.76 (95% confidence interval (CI), 0.75–0.77). Among COVID-19 patients, the aOR of developing severe COVID-19 illness was 0.72 (95% CI, 0.68–0.76) between the influenza-vaccination group and the no-influenza-vaccination group. When the influenza-vaccination group and the other-vaccination group were compared, the aOR of COVID-19 infection was 0.95 (95% CI, 0.93–0.97), and the aOR of developing a severe COVID-19 illness was 0.95 (95% CI, 0.80–1.13). The influenza vaccine may marginally protect people from COVID-19 infection.

Amidst pandemic and racial upheaval: Where Asian Americans Fit

2020 ◽  
pp. 1-17
Author(s):  
Whitney Hua ◽  
Jane Junn
Keyword(s):  
United States ◽  
Asian Americans ◽  
Racial Inequality ◽  
White Supremacy ◽  
The United States ◽  
Structural Racism ◽  
Global Pandemic ◽  
American Capitalism ◽  
Racial History ◽  
History Of

Abstract As racial tensions flare amidst a global pandemic and national social justice upheaval, the centrality of structural racism has renewed old questions and raised new ones about where Asian Americans fit in U.S. politics. This paper provides an overview of the unique racial history of Asians in the United States and analyzes the implications of dynamic racialization and status for Asian Americans. In particular, we examine the dynamism of Asian Americans' racial positionality relative to historical shifts in economic-based conceptions of their desirability as workers in American capitalism. Taking history, power, and institutions of white supremacy into account, we analyze where Asian Americans fit in contemporary U.S. politics, presenting a better understanding of the persistent structures underlying racial inequality and developing a foundation from which Asian Americans can work to enhance equality.

Foundation News: Impact of the pandemic on the GWB drinking water project in the Nepal Himalaya region

2021 ◽  
Vol 40 (4) ◽  
pp. 242-243
Author(s):  
Kirsten Nicholson ◽  
Klaus Neumann ◽  
Subodh Sharma ◽  
Lakpa Thering Sherpa
Keyword(s):  
Water Quality ◽  
Drinking Water ◽  
National Park ◽  
The United States ◽  
High Mountain ◽  
Geologic Mapping ◽  
Global Pandemic ◽  
Vulnerability To Climate Change ◽  
Sagarmatha National Park ◽  
Water Vulnerability

In 2019, after almost a decade of working on water quality in the Himalayas, we submitted a proposal to Geoscientists Without Borders® (GWB) titled “Understanding high mountain aquifers to source drinking water in Sagarmatha National Park.” The project involves a combination of water-quality and quantity measurements, geologic mapping, and an electrical resistivity tomography survey. The goal of the project is to help two communities (Phortse and Lobuche within Sagarmatha National Park in Nepal) minimize their water vulnerability to climate change and earthquakes. The project team includes researchers and students from the United States and Nepal, as well as nongovernmental organizations, government agencies, and community councils. In the proposal, we identified physical health and altitude as the primary risks that could hinder the success of the project. Like everyone else in early 2019, we had no way to foresee the events of 2020, which would almost completely derail our project. Health has turned out to be the major hinderance. The irony of the global pandemic is how much it has impacted the work of the U.S.-based team and how little it has impacted the necessity of the project.

Impacts of Social Distancing on Pedestrian Behavior and Risk Perception

2021 ◽  
Vol 65 (1) ◽  
pp. 1302-1306
Author(s):  
Kyra B. Phillips ◽  
Kelly N. Byrne ◽  
Branden S. Kolarik ◽  
Audra K. Krake ◽  
Young C. Bui ◽  
...  
Keyword(s):  
United States ◽  
Risk Perception ◽  
Perceived Risk ◽  
Close Contact ◽  
The United States ◽  
Survey Study ◽  
Pedestrian Behavior ◽  
Social Distancing ◽  
Global Pandemic ◽  
Over Time

Since COVID-19 transmission accelerated in the United States in March 2020, guidelines have recommended that individuals wear masks and limit close contact by remaining at least six feet away from others, even while outdoors. Such behavior is important to help slow the spread of the global pandemic; however, it may require pedestrians to make critical decisions about entering a roadway in order to avoid others, potentially creating hazardous situations for both themselves and for drivers. In this survey study, we found that while overall patterns of self-reported pedestrian activity remained largely consistent over time, participants indicated increased willingness to enter active roadways when encountering unmasked pedestrians since the COVID-19 pandemic began. Participants also rated the risks of encountering unmasked pedestrians as greater than those associated with entering a street, though the perceived risk of passing an unmasked pedestrian on the sidewalk decreased over time.

Caring for an Aging Population in a Post-Pandemic World: Emerging Trends in the U.S. Older Adult Care Industry

2021 ◽  
Author(s):  
Lu Kong ◽  
Kejia Hu ◽  
Matthew Walsman
Keyword(s):  
Older Adult ◽  
Digital Communication ◽  
The United States ◽  
Adult Care ◽  
Communication Tools ◽  
Care Industry ◽  
Care Services ◽  
Global Pandemic ◽  
Emerging Trends ◽  
The U.S

This paper examines older adult care services during the outbreak of the COVID-19 global pandemic. Specifically, it investigates emerging developments initiated or augmented by the pandemic and discusses their permanency in a postpandemic world. Primary survey data are collected from both older adult care-providing organizations (supply) and individuals receiving or considering care (demand) in the United States. Qualitative support from various sources supplements the surveys. The results indicate a movement toward deinstitutional care options, which began prepandemic but intensified during the outbreak. Care organizations confirm this development, reporting more occupancy-related concerns. Findings also suggest that telehealth and digital communication tools have substantially expanded. Benefits, issues, and future projections of these trends are discussed, and some suggestions for industry reform are proposed. These results illuminate many actionable ideas for various stakeholders, including older adults, industry practitioners, and policymakers.

Emergency preparedness during a global pandemic: Individual preparedness for COVID-19

2020 ◽  
Vol 18 (7) ◽  
pp. 99-113
Author(s):  
Kelly L. Brown, PhD
Keyword(s):  
United States ◽  
Emergency Preparedness ◽  
The United States ◽  
Global Pandemic

 Existing research on individual preparedness in the United States indicates that we are generally unprepared for disasters. While there is an abundance of research on emergency preparedness, there are gaps in our knowledge. For example, the results of extant research are unclear regarding what factors influence individual preparedness. The preparedness literature is also limited in the types of disasters examined and in understanding the timing of preparedness activities. The current COVID-19 global pandemic provides a tragic but albeit unique opportunity to address these limitations of previous research and examine emergency preparedness activities before and immediately following the onset of the COVID-19 outbreak in the United States. This research is further distinctive because it examines preparedness activities related to the global pandemic rather than other types of disasters. Policy and research implications of the findings are presented.

scholarly journals Exploratory Analysis into the in vitro and in silico Activity of E. fusca Lour. (Fabaceae) Elucidates Substantial Antiplasmodial Activity of the Plant

2021 ◽  
Author(s):  
Saiful Arefeen Sazed ◽  
Ohedul Islam ◽  
Sarah L. Bliese ◽  
Muhammad Riadul Haque Hossainey ◽  
Jakaria Shawon ◽  
...  
Keyword(s):  
Antimalarial Drug ◽  
Simulation Analysis ◽  
Antimalarial Activity ◽  
Dynamics Simulation ◽  
Drug Candidate ◽  
Phytochemical Investigation ◽  
High Degree ◽  
Emergence Of Resistance ◽  
First Time

The exploration of alternative antimalarial therapeutics is a requisite for the emergence of resistance against Artemisinin. Considering the required cost and time length of classical small molecule drug discovery process, phytochemical screening of traditionally used medicinal plant which are repertoire of active compounds with antimalarial activity has become popular. To investigate the antimalarial property of traditionally used medicinal plants, a number of Erythrina spp have been reviewed systematically where less studied E. fusca has been selected for further analysis. Phytochemical investigation yielded five compounds namely; Phaseolin, Phytol, &beta;-amyrin, Lupeol, and Stigmasterol. In-vitro antimalarial drug sensitivity HRP-II ELISA was carried out against chloroquine (CQ) sensitive 3D7 and CQ-resistant Dd2 strains. Extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC50 4.94 &ndash; 22 &micro;g/mL) and these compounds have been reported here for the first time. Molecular docking analysis showed high binding energy (&minus;9.0 &plusmn; 0.32 kcal/mole) indicating high degree of interaction between Phaseolin and 14 clinically important Plasmodium falciparum proteins at the active site. Stable interaction was also observed between ligand and protein from molecular dynamics simulation analysis with high free energy (&minus;75.156 &plusmn; 11.459) that substantiates the potential of Phaseolin as an antimalarial drug candidate.

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