Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.

Adult Asylum Seekers from the Middle East Including Syria in Central Europe: What Are Their Health Care Problems?

Background Forced displacement related to persecution and violent conflict has reached a new peak in recent years. The primary aim of this study is to provide an initial overview of the acute and chronic health care problems of asylum seekers from the Middle East, with special emphasis on asylum seekers from Syria. Methods Our retrospective data analysis comprised adult patients presenting to our emergency department between 01.11.2011 and 30.06.2014 with the official resident status of an “asylum seeker” or “refugee” from the Middle East. Results In total, 880 patients were included in the study. Of these, 625 (71.0%) were male and 255 (29.0%) female. The median age was 34 (range 16–84). 222 (25.2%) of our patients were from Syria. The most common reason for presentation was surgical (381, 43.3%), followed by medical (321, 36.5%) and psychiatric (137, 15.6%). In patients with surgical presentations, trauma-related problems were most common (n = 196, 50.6%). Within the group of patients with medical presentation, acute infectious diseases were most common (n = 141, 43.9%), followed by neurological problems (n = 70, 21.8%) and gastrointestinal problems (n = 47, 14.6%). There were no differences between Syrian and non-Syrian refugees concerning surgical or medical admissions. The most common chronic disorder of unclear significance was chronic gastrointestinal problems (n = 132, 15%), followed by chronic musculoskeletal problems (n = 108, 12.3%) and chronic headaches (n = 78, 8.9%). Patients from Syria were significantly younger and more often suffered from a post-traumatic stress disorder than patients of other nationalities (p<0.0001, and p = 0.05, respectively). Conclusion Overall a remarkable number of our very young group of patients suffered from psychiatric disorders and unspecified somatic symptoms. Asylum seekers should be carefully evaluated when presenting to a medical facility and physicians should be aware of the high incidence of unspecified somatic symptoms in this patient population.In general, there is no major difference between asylum seekers from Syria when compared to other nationalities of asylum seekers from the Middle East.

Distribution and variability of deformed wing virus of honeybees (Apis mellifera) in the Middle East and North Africa.

Three hundred eleven honeybee samples from twelve countries in the Middle East and North Africa (MENA) (Jordan, Lebanon, Syria, Iraq, Egypt, Libya, Tunisia, Algeria, Morocco, Yemen, Palestine and Sudan) were analyzed for the presence of deformed wing virus (DWV). The prevalence of DWV throughout the MENA region was pervasive, but variable. The highest prevalence was found in Lebanon and Syria, with prevalence dropping in Palestine, Jordan and Egypt before increasing slightly moving westwards to Algeria and Morocco Phylogenetic analysis of a 194 nucleotide section of the DWV Lp gene did not identify any significant phylogenetic resolution among the samples, although the sequences did show consistent regional clustering, including an interesting geographic gradient from Morocco through North Africa to Jordan and Syria. The sequences revealed several clear variability hotspots in the deduced amino acid sequence, that furthermore showed some patterns of regional identity. Furthermore, the sequence variants from the Middle East and North Africa appear more numerous and diverse than those from Europe. This article is protected by copyright. All rights reserved.

Japan and the Middle East after the Arab Spring

本稿は、中東における問題や紛争に対する日本の政策を考察し、中長期的な視野に立った日本の国益追求のためにはどのような選択肢が考えられるかを論じる。そのために、イランの核開発問題とシリアの市民戦争をケースとしてとりあげる。戦後の日本は中東での問題や紛争に対して、地域内諸国およびアメリカとの関係を同時に維持するために、双方の均衡を図る政策を打ち出してきたが、冷戦後には米国寄りの傾向が多く見られた。現在中東では、アラブの春の展望は不透明な部分が多い。日本は中東との関係において、問題や紛争の性質によっては負の遺産を抱える欧米とは一線を画した独自の政策とアプローチを打ち出すことが、中東資源国との関係の強化と拡大や中東市場の発展と安定には望ましいと考える。また同時に、今後の米国の中東における国益の変化が考えられることも要因ととらえ、本稿は冷戦期にみられたような、より均衡のとれた立場を打ち出し、より広い概念をもとに基づいた効果的なソフトパワーの行使を提唱する。

Sovereignty and Intervention in the Middle East: From the Fall of the Ottoman Empire to the Arab Spring

This research provides an institutional explanation of the practices of external intervention in the Arab state system from the fall of the Ottoman Empire in 1922 to the Arab Spring. My explanation consists of two institutional variables: sovereignty and inter-state borders. I examine the changes in regional and international norms of sovereignty and their impact on the practices of external intervention in the Arab state system. I also examine the impact of the level of institutionalization of inter-state borders in the Arab World on the practices of external intervention. I argue that changes in regional and international norms of sovereignty and changes in the level of institutionalization of inter-state borders have constituted the significant variation over time in both the frequency and type of external intervention in the Arab state system from 1922 to the present. My institutional explanation and findings seriously challenge the traditional accounts of sovereignty and intervention in the Arab World, including the cultural perspectives that emphasize the conflict between sovereignty, Arabism, and Islam, the constructivist accounts that emphasize the regional norm of pan-Arabism, the comparative politics explanations that focus on the domestic material power of the Arab state, the post-colonial perspectives that emphasize the artificiality of the Arab state, and the realist accounts that focus on great powers and the regional distribution of power in the Middle East. This research also contributes to International Relations Theory. I construct a new analytical framework to study the relations between sovereignty, borders, and intervention, combining theoretical elements from the fields of Role Theory, Social Constructivism, and Institutionalization. Methodologically, this research includes both quantitative and qualitative analysis. I conduct content analysis of official documents of Arab states and the Arab League, Arabic press documents, and Arab political thought. I also utilize quantitative data sets on international intervention.

New Middle East Cold War: Saudi Arabia and Iran's Rivalry

The competing powers of Saudi Arabia and Iran continue to redress and reverse the strategic imbalance and direction of the Middle East’s regional politics. The 1979 Iranian Revolution catapulted these two states into an embittered rivalry. The fall of Saddam Hussein following the 2003 U.S. led invasion, the establishment of a Shi’ite Iraq and the 2011 Arab Uprisings have further inflamed tensions between Saudi Arabia and Iran. Iran and Saudi Arabia have not confronted each other militarily, but rather have divided the region into two armed camps on the basis of political and religious ideology in seeking regional allies and promulgating sectarianism as they continue to exploit the region’s weak states in a series of proxy wars ranging from conflicts in Iraq to Lebanon. The Saudi-Iranian strategic and geopolitical rivalry is further complicated by a religious and ideological rivalry, as tensions represent two opposing aspirations for Islamic leadership with two vastly differing political systems. The conflict is between Saudi Arabia, representing Sunni Islam via Wahhabism, and Iran, representing Shi’ite Islam through Khomeinism. The nature of the Saudi-Iranian rivalry has led many Middle East experts to identify their rivalry as a “New Middle East Cold War.” The Saudi-Iranian rivalry has important implications for regional stability and U.S. national security interests. Therefore, this thesis seeks to address the question: Is a cold war framework applicable when analyzing the Saudi Arabian and Iranian relationship?

Middle East and South Asia, 1903 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A map of the countries between Constantinople and Calcutta : including Turkey in Asia, Persia, Afghanistan and Turkestan. It was published by Edward Stanford in 1903. Scale 1:6,969,600. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Asia North Lambert Conformal Conic coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, roads, railroads, ferry routes, shoreline features, and more. Relief shown by hachures and spot heights. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Does the key to a WMD-free Middle East lie in a nuclear Iran? CEPS Commentary, 10 June 2013

After the presidential elections on June 14th, the Iranian regime will continue its catch-me-if-you-can game with the international community until it has reached the nuclear threshold. Paradoxically, the key to a solution on the nuclear issue might just lie in discussions on a WMD-free Middle East, but only after Iran has obtained nuclear military capability. At that point, and in the context of a new arms race, both regional and international players may be persuaded that the Middle East has more to gain from negotiations on non-proliferation than from prolonged isolation and the prospect of intractable war.

Vanishing lines in the sand – Why a new map of the Middle East is necessary. CEPS Commentary, 1 October 2013

As the stalemate in Syria drags on, territorial divisions in the country are becoming more entrenched and the civil war is spreading to Syria’s neighbours; aggravating long-standing sectarian divisions in the whole region. In the view of Steven Blockmans, a lasting agreement cannot be reached in the Middle East if world powers stick to infamous 1916 Sykes-Picot Agreement in which France and the UK secretly dealt with what came to be called the ‘Syria Question’. Any way out of the quagmire will require a grand bargain – one that establishes a new order in the whole region and draws borders accordingly.