Therapeutic approaches against coronaviruses acute respiratory syndrome

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Clofarabine Commandeers the RNR-alpha-ZRANB3 Nuclear Signaling Axis

Ribonucleotide reductase (RNR) is an essential enzyme in DNA biogenesis and a target of several chemotherapeutics. Here, we investigate how antileukemic drugs (e.g., clofarabine [CIF]) that target one of the two subunits of RNR, RNR-alpha, affect noncanoni ...

CELL PRESS2020

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

Florence Pojer, Kelvin Ka Ching Lau, Oliver Hantschel, Tim Kükenshöner, Grégory La Sala

The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere ...

Nature Research2020

Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein

Henning Paul-Julius Stahlberg, David Hacker, Florence Pojer, Kelvin Ka Ching Lau, Dongchun Ni

The human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, ...

2020

COVID-19 epidemic in Switzerland: on the importance of testing, contact tracing and isolation

Marcel Salathé

Switzerland is among the countries with the highest number of coronavirus disease-2019 (COVID-19) cases per capita in the world. There are likely many people with undetected SARS-CoV-2 infection because testing efforts are currently not detecting all infec ...

2020

Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures

Andrea Rinaldo, Enrico Bertuzzo, Lorenzo Mari, Luca Carraro, Marino Gatto

The spread of coronavirus disease 2019 (COVID-19) in Italy prompted drastic measures for transmission containment. We examine the effects of these interventions, based on modeling of the unfolding epidemic. We test modeling options of the spatially explici ...

National Academy of Sciences2020

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Jacques Fellay, Rui Yang, Jie Chen, Yu Zhang, Xavier Duval, Peng Zhang, Qian Zhang, Zhiyong Liu, Juan Li

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF ...

American Association for the Advancement of Science2020

Marker-Free Automatic Quantification of Drug-Treated Cardiomyocytes with Digital Holographic Imaging

Gerardo Turcatti, Benjamin Rappaz, Fabien Kuttler, Bokyoung Kim, Pierre Marquet

We use quantitative phase digital holographic microscopy (QP-DHM) to image and quantify the beating movement of cardiomyocytes, derived from induced pluripotent stem cells (iPSCs), in control and drug-treated conditions. The development of an analysis algo ...

AMER CHEMICAL SOC2020

A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus

Gerardo Turcatti, Fabien Kuttler

Human adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus ...

2020

Targeting liver stage malaria with metformin

Leonardo Filipe Lemos Rocha

Despite an unprecedented 2 decades of success, the combat against malaria - the mosquito-transmitted disease caused by Plasmodium parasites - is no longer progressing. Efforts toward eradication are threatened by the lack of an effective vaccine and a rise ...

2019

Multimodal imaging and high-throughput image-processing for drug screening on living organisms on-chip

Michaël Unser, Johan Auwerx, Martinus Gijs, Matteo Cornaglia, Laurent Mouchiroud, Daniel Migliozzi, Virginie Sophie Uhlmann

A major step for the validation of medical drugs is the screening on whole organisms, which gives the systemic information that is missing when using cellular models. Caenorhabditis elegans is a soil worm that catches the interest of researchers who study ...

SPIE Society of Photo-optical Instrumentation Engineers2019

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