scholarly journals High-resolution structures of the SARS-CoV-2 2′-O-methyltransferase reveal strategies for structure-based inhibitor design

2020 ◽  
Vol 13 (651) ◽  
pp. eabe1202 ◽  
Author(s):  
Monica Rosas-Lemus ◽  
George Minasov ◽  
Ludmilla Shuvalova ◽  
Nicole L. Inniss ◽  
Olga Kiryukhina ◽  
...  
Keyword(s):  
Protein Translation ◽  
Binding Pocket ◽  
Viral Mrnas ◽  
Structure Based Drug Design ◽  
Nucleotide Binding Sites ◽  
Antiviral Therapies ◽  
Global Pandemic ◽  
The Face ◽  
Binding Groove ◽  
Immune Detection

There are currently no antiviral therapies specific for SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2′-O-methyltransferase complex, which methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG). We also solved structures for nsp16-nsp10 in complex with the methylated Cap-0 analog m7GpppA and either SAM or SAH. Comparative analyses between these structures and published structures for nsp16 from other betacoronaviruses revealed flexible loops in open and closed conformations at the m7GpppA-binding pocket. Bound sulfates in several of the structures suggested the location of the ribonucleic acid backbone phosphates in the ribonucleotide-binding groove. Additional nucleotide-binding sites were found on the face of the protein opposite the active site. These various sites and the conserved dimer interface could be exploited for the development of antiviral inhibitors.

scholarly journals Structure of SARS-CoV-2 2′-O-methyltransferase heterodimer with RNA Cap analog and sulfates bound reveals new strategies for structure-based inhibitor design

2020 ◽  
Author(s):  
Monica Rosas-Lemus ◽  
George Minasov ◽  
Ludmilla Shuvalova ◽  
Nicole Inniss ◽  
Olga Kiryukhina ◽  
...  
Keyword(s):  
Protein Translation ◽  
Binding Pocket ◽  
Viral Mrnas ◽  
Structure Based Drug Design ◽  
Nucleotide Binding Sites ◽  
Antiviral Therapies ◽  
Global Pandemic ◽  
The Face ◽  
Binding Groove ◽  
Immune Detection

AbstractThere are currently no antiviral therapies specific against SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an X-ray crystallographic study of the nsp16/nsp10 2′-O-methyltransferase complex that methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. Heterodimer structures are determined with the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH) or the SAH analog sinefungin (SFG). Furthermore, structures of nsp16/nsp10 with the methylated Cap-0 analog (m7GpppA) and SAM or SAH bound were obtained. Comparative analysis revealed flexible loops in open and closed conformations at the m7GpppA binding pocket. Bound sulfates in several structures suggested the location of the phosphates in the ribonucleotide binding groove. Additional nucleotide binding sites were found on the face of the protein opposite the active site. These various sites and the conserved dimer interface could be exploited for development of antiviral inhibitors.

Too WEIRD, Too Fast: Preprints about COVID-19 in the Psychological Sciences

2020 ◽  
Author(s):  
Arathy Puthillam
Keyword(s):  
Overwhelming Majority ◽  
Global Pandemic ◽  
The Us ◽  
The World ◽  
The Face ◽  
Conducting Research ◽  
Psychological Studies

That American and European participants are overrepresented in psychological studies has been previously established. In addition, researchers also often tend to be similarly homogenous. This continues to be alarming, especially given that this research is being used to inform policies across the world. In the face of a global pandemic where behavioral scientists propose solutions, we ask who is conducting research and on what samples. Forty papers on COVID-19 published in PsyArxiV were analyzed; the nationalities of the authors and the samples they recruited were assessed. Findings suggest that an overwhelming majority of the samples recruited were from the US and the authors were based in US and German institutions. Next, men constituted a large proportion of primary and sole authors. The implications of these findings are discussed.

scholarly journals William James and the Sustainable Transformation of Values, with a Case Study for Rethinking the American Dream

Human Arenas ◽  
2021 ◽  
Author(s):  
Paul Croce
Keyword(s):  
Economic Growth ◽  
Social Transformation ◽  
American Dream ◽  
William James ◽  
Social Issues ◽  
Virus Spread ◽  
Global Pandemic ◽  
The Face ◽  
The Many

AbstractThis article addresses the call of the Psychology of Global Crises conference for linkage of academic work with social issues in three parts: First, examples from conference participants with their mix of bold calls for social transformation and realization of limits, a combination that generated few clear paths to achieving them. Second, presentation of Jamesian practical idealism with psychological insights for moving past impediments blocking implementation of ideals. And third, a case study of impacts from the most recent prominent crisis, the global pandemic of 2020, which threatens to exacerbate the many crises that had already been plaguing recent history. The tentacles of COVID’s impact into so many problems, starting with economic impacts from virus spread, present an opportunity to rethink the hope for constant economic growth, often expressed as the American Dream, an outlook that has driven so many of the problems surging toward crises. Jamesian awareness of the construction of ideological differences and encouragement of listening to those in disagreement provide not political solutions, but psychological preludes toward improvements in the face of crises.

scholarly journals Social policy in the face of a global pandemic: Policy responses to the COVID ‐19 crisis

2021 ◽  
Vol 55 (2) ◽  
pp. 249-260
Author(s):  
Daniel Béland ◽  
Bea Cantillon ◽  
Rod Hick ◽  
Amílcar Moreira
Keyword(s):  
Social Policy ◽  
Policy Responses ◽  
Global Pandemic ◽  
The Face

From IRL (in-real-life) to URL: Capturing the art biennial amid COVID-19

2021 ◽  
Vol 8 (2-3) ◽  
pp. 291-311
Author(s):  
(Gwen) Kuan-ying Kuo
Keyword(s):  
Real Life ◽  
Art World ◽  
The Public ◽  
Global Pandemic ◽  
International Exhibitions ◽  
Art Scene ◽  
Before And After ◽  
The Face ◽  
The Taiwan Strait ◽  
Potential Shifts

In early 2020, the unforeseen COVID-19 has brought the art world to its knees, particularly the contemporary art scene needs viewers and feedback to survive. Artists require new channels connecting them with their audiences, while artists’ work needs to be seen and appreciated by the public to sustain its value. In the face of social distancing restrictions and limited visitors, however, many international exhibitions are forced to cancel or postponed. With less to no patronage, will the global pandemic bring the end of the art world? As the global pandemic has forced most social and cultural events moving online, the art biennials are no exception. This article examines the art biennial, the Olympics of the art world, to rediscover the meaning of ‘art’ before and after COVID-19. Integrating virtual presentation and digital campaign between the Taipei Biennial and the Shanghai Biennale, the first running art biennials across the Taiwan Strait, this article analyses and presents the art world’s potential shifts in the post-pandemic future.

scholarly journals Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal

2020 ◽  
Vol 18 (4) ◽  
pp. 366-369 ◽  
Author(s):  
Masumi Ueda ◽  
Renato Martins ◽  
Paul C. Hendrie ◽  
Terry McDonnell ◽  
Jennie R. Crews ◽  
...  
Keyword(s):  
United States ◽  
Cancer Treatment ◽  
Cancer Care ◽  
Rapid Change ◽  
The United States ◽  
Shared Vision ◽  
Health Crisis ◽  
Global Pandemic ◽  
The Face ◽  
Snohomish County

The first confirmed case of coronavirus disease 2019 (COVID-19) in the United States was reported on January 20, 2020, in Snohomish County, Washington. At the epicenter of COVID-19 in the United States, the Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, and University of Washington are at the forefront of delivering care to patients with cancer during this public health crisis. This Special Feature highlights the unique circumstances and challenges of cancer treatment amidst this global pandemic, and the importance of organizational structure, preparation, agility, and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.

scholarly journals TERMINATION OF EMPLOYEES’ EMPLOYMENT DURING COVID-19: A GUIDE FOR EMPLOYERS IN ACCORDANCE WITH EMPLOYMENT LAW

2021 ◽  
Vol 6 (22) ◽  
pp. 138-146
Author(s):  
Mumtaj Hassan ◽  
Anis Shuhaiza Md Salleh ◽  
Yusramizza Md Isa @ Yusuff
Keyword(s):  
Well Being ◽  
International Labor Organization ◽  
Secondary Sources ◽  
Legal Documents ◽  
Global Pandemic ◽  
International Labor ◽  
The Face ◽  
Huge Impact ◽  
Business Profit ◽  
Almost All

The global pandemic of COVID-19 has endangered the human and economic well-being in the world. It also has a huge impact on almost all industries at home and abroad. The International Labor Organization (ILO) expects the pandemic to increase layoffs and unemployment worldwide. In this case, employers are certainly in a dilemma, each looking for and juggling between workers' income and business profit. Thus, this article explores the aspect of termination of employees’ employment through library-based research that focuses on the use of statutes, courts’ cases, legal documents, and scholarly writings published in journals. Descriptive and critical methods are used to analyse the primary and secondary sources referred to. This article stresses that there are procedures and laws which employers need to obey in order to address the excessive number of employees in the face of pandemics. Dismissal of employees should not be done arbitrarily without justifications and procedures that have been outlined by law. The discussion ended with suggestions to employers so that any layoffs can be blocked and minimized.

scholarly journals The key features of SARS-CoV-2 leader and NSP1 required for viral escape of NSP1-mediated repression

2021 ◽  
Author(s):  
Lucija Bujanic ◽  
Olga Shevchuk ◽  
Nicolai von Kuegelgen ◽  
Katarzyna Ludwik ◽  
David Koppstein ◽  
...  
Keyword(s):  
Drug Targets ◽  
Early Stage ◽  
Nonstructural Protein ◽  
Viral Escape ◽  
Cellular Mechanisms ◽  
Viral Mrnas ◽  
Stem Loop ◽  
Nonstructural Protein 1 ◽  
Global Pandemic ◽  
Cellular Mrnas

SARS-CoV-2, responsible for the ongoing global pandemic, must overcome a conundrum faced by all viruses. To achieve its own replication and spread, it simultaneously depends on and subverts cellular mechanisms. At the early stage of infection, SARS-CoV-2 expresses the viral nonstructural protein 1 (NSP1), which inhibits host translation by blocking the mRNA entry tunnel on the ribosome; this interferes with the binding of cellular mRNAs to the ribosome. Viral mRNAs, on the other hand, overcome this blockade. We show that NSP1 enhances expression of mRNAs containing the SARS-CoV-2 leader. The first stem-loop (SL1) in viral leader is both necessary and sufficient for this enhancement mechanism. Our analysis pinpoints specific residues within SL1 (three cytosine residues at the positions 15, 19 and 20) and another within NSP1 (R124) which are required for viral evasion, and thus might present promising drug targets. Additionally, we carried out analysis of a functional interactome of NSP1 using BioID and identified components of anti-viral defense pathways. Our analysis therefore suggests a mechanism by which NSP1 inhibits the expression of host genes while enhancing that of viral RNA. This analysis helps reconcile conflicting reports in the literature regarding the mechanisms by which the virus avoids NSP1 silencing.

scholarly journals Risk and the Rule of law

2020 ◽  
Vol 16 (3) ◽  
Author(s):  
Janet McLean
Keyword(s):  
Rule Of Law ◽  
Moral Issues ◽  
The Rule Of Law ◽  
Global Pandemic ◽  
The Face

In this article the author argues for the importance of law even in the face of a global pandemic, suggests some ways that law helps to reveal and articulate the moral issues at stake, and sketches the legal controversies surrounding the Covid-19 lockdown.

Introduction

2021 ◽  
pp. 1-38
Author(s):  
Sara E. Gorman ◽  
Jack M. Gorman
Keyword(s):  
United States ◽  
Hemorrhagic Fever ◽  
The United States ◽  
Ebola Hemorrhagic Fever ◽  
Global Pandemic ◽  
The Face ◽  
Grave Problem ◽  
Novel Coronavirus ◽  
Vocal Minority

In 2014, a deadly epidemic of Ebola hemorrhagic fever ravaged three countries in West Africa. While the disease barely hit the United States, it caused widespread panic that sometimes threatened the safety of African immigrants in the United States. Five years later, a global pandemic of a novel coronavirus, later named COVID-19, quickly picked up speed around the world. In the face of a serious and very real threat, many Americans ignored the warnings and a vocal minority even insisted that the pandemic was not real. While the particulars of each of these examples might be quite different, they have something very important in common: science denial. This introductory chapter provides an overview of how such widespread science denialist views come into existence and how they spread. The authors outline the eight chapters of this book, which go into depth on different psychological mechanisms behind this phenomenon. Finally, they provide a preview of some of the solutions we have devised in response to this grave problem.

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