A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Promise of paradise: recreational and retirement communities in the United States since 1950

Hubert B. Stroud.xi, 220 p. : ill., maps ; 24 cm

The Land Development Corporation: A System for Selling Rural Real Estate

This research illustrates ways in which rural real estate is converted into potential vacation home sites by large land development corporations. The individual and previously disorganized approach to selling property is replaced by an organized framework that is designed to create a demand for rural real estate.Unfortunately, development is progressing without serious or adequate consideration being given to a number of specific problems. Developers and local governmental officials often fail to consider the environmental impact of these developments, the adequacy of service facilities being provided or the direct and indirect public costs associated with this type of developmental activity. Because of these shortcomings and others, serious questions arise concerning the desirability of this kind of developmental activity for rural areas. Copyright American Real Estate and Urban Economics Association.

Developing a Sustainable Water Supply in the American West: The Case of Rio Rancho, New Mexico

Suburban and urban communities in the American West are challenged by rapid population growth combined with limited natural resources. Supporting sustainable development is of great concern in this region and in similar regions throughout the world. This research examines the sustainability of the water supply within a rapidly growing suburban city in the American West. The city, Rio Rancho, New Mexico, began as an interstate land sales operation and rapidly became a “boom” town, in part because of its location near metropolitan Albuquerque. Because of a very limited water supply and an increasing demand for water associated with population growth, Rio Rancho has created a water management strategy that includes water conservation, water reuse, aquifer recharge, and other water saving techniques, as well as education and community outreach concerning water issues. Initial conservation and management strategies have been successful in reducing system-wide per capita water usage by roughly 39% between 2000 and 2015. This decrease occurred in spite of a substantial increase in population. This paper outlines how current and future efforts can help to achieve water supply sustainability while promoting suburban development, even in an arid environment

Platted lands and growth management in the Evergreen State

Washington State\u27s Growth Management Act provides an effective means to guide growth but the state has had land management problems arising from pre-existing subdivision plans ( platted lands ). However, there are several steps available to deal with the potential land use conflicts arising from these undeveloped subdivisions. These steps and the lessons from Washington state are applicable to any country, state, or municipality facing a change in land subdivision law or dealing with historical matters of vested rights