The Masdar Development - Climate Engineering for a Carbon-neutral City

As member of the design team - consisting of the architects, traffic planners, infrastructure and renewable energy systems engineers and us as climate engineers - for the Masdar City Master Plan in Abu Dhabi, we developed a new and most holistic approach of defining sustainable urban development: The six square kilometer city, designed by Foster and Partner for the Abu Dhabi Future Energy Company, is eventually to house 50,000 people in accordance with WWF One Planet Living sustainability standards, which include specific targets for the city's ecological footprint. Masdar City plans to exceed the requirements of the 10 sustainability principles - zero carbon, zero waste, sustainable transport, sustainable materials, sustainable food, sustainable water, habitats and wildlife, culture and heritage, equity and fair trade, and health and happiness

Synthetic α-Helical Peptides as Potential Inhibitors of the ACE2 SARS-CoV-2 Interaction

During viral cell entry, the spike protein of SARS-CoV-2 binds to the α1-helix motif of human angiotensin-converting enzyme 2 (ACE2). Thus, alpha-helical peptides mimicking this motif may serve as inhibitors of viral cell entry. For this purpose, we employed the rigidified diproline-derived module ProM-5 to induce α-helicity in short peptide sequences inspired by the ACE2 α1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH2 as a relevant section of α1, a series of peptides, N-capped with either Ac-βHAsp-[ProM-5] or Ac-βHAsp-PP, were prepared and their α-helicities were investigated. While ProM-5 clearly showed a pronounced effect, an even increased degree of helicity (up to 63 %) was observed in sequences in which non-binding amino acids were replaced by alanine. The binding affinities of the peptides towards the spike protein, as determined by means of microscale thermophoresis (MST), revealed only a subtle influence of the α-helical content and, noteworthy, led to the identification of an Ac-βHAsp-PP-capped peptide displaying a very strong binding affinity (KD=62 nM)

Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5′-untranslated region (5′-UTR) of SARS-CoV-2. The most promising candidate identified in initial reporter assays, termed siCoV6, targets the leader sequence of the virus, which is present in the genomic as well as in all subgenomic RNAs. In assays with infectious SARS-CoV-2, it reduced replication by two orders of magnitude and prevented the development of a cytopathic effect. Moreover, it retained its activity against the SARS-CoV-2 alpha variant and has perfect homology against all sequences of the delta variant that were analyzed by bioinformatic means. Interestingly, the siRNA was even highly active in virus replication assays with the SARS-CoV-1 family member. This work thus identified a very potent siRNA with a broad activity against various SARS-CoV viruses that represents a promising candidate for the development of new treatment options

Polysulfate hemmen durch elektrostatische Wechselwirkungen die SARS-CoV-2-Infektion

Wir zeigen, dass negativ geladene Polysulfate durch elektrostatische Wechselwirkungen an das Spike-Protein von SARS-CoV-2 binden. Durch einen Plaquereduktionstest verglichen wir die hemmende Wirkung von Heparin, Pentosanpolysulfat, linearem Polyglycerolsulfat (LPGS) und hyperverzweigtem Polyglycerolsulfat (HPGS) gegengber SARSCoV-2. Dabei ist das synthetische LPGS der vielversprechendste Inhibitor mit IC50=67 μgmL-1 (ca. 1,6 μm) und zeigt eine 60-fach hçhere virushemmende Aktivität als Heparin (IC50=4084 μgmL-1) bei zugleich deutlich geringerer gerinnungshemmender Aktivität. Außerdem konnten wir durch Moleküldynamiksimulationen bestätigen, dass LPGS stärker an das Spike-Protein bindet als Heparin selbst und dass LPGS sogar noch stärker an die Spike-Proteine der neuen N501Yund E484K-Varianten bindet. Unsere Studien belegen, dass die Aufnahme von SARS-CoV-2 in Wirtzellen über elektrostatische Wechselwirkungen blockiert werden kann. Deshalb kann LPGS als vielversprechender Prototyp für das Design weiterer neuartiger viraler Inhibitoren von SARS-CoV-2 herangezogen werden

Polysulfates block SARS-CoV-2 uptake through electrostatic interactions

Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC50) of 67 μg/mL (approx.1.6 μM). This synthetic polysulfates exhibit more than 60-fold higher virus inhibitory activity than heparin (IC50: 4084μg/mL), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind stronger to the spike protein than heparin, and that LPGS can interact even morewith the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interaction, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2

Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants

As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C60 fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit infection of SARS-CoV-2 variants in vitro. Effective inhibitory concentrations in the millimolar range highlight the significance of bare fullerene's hydrophobic moiety and electrostatic interactions of polysulfates with surface proteins of SARS-CoV-2. Furthermore, microscale thermophoresis measurements support that fullerene linear polyglycerol sulfates interact with the SARS-CoV-2 virus via its spike protein, and highlight importance of electrostatic interactions within it. All-atom molecular dynamics simulations reveal that the fullerene binding site is situated close to the receptor binding domain, within 4 nm of polyglycerol sulfate binding sites, feasibly allowing both portions of the material to interact simultaneously