ACE peptide

SARS-CoV-2 infection is a new threat to global public health in the 21(st)century (2020), which has now rapidly spread around the globe causing severe pneumonia often linked to Acute Respiratory Distress Syndrome (ARDS) and hyperinflammatory syndrome. SARS-CoV-2 is highly contagious through saliva droplets. The structural analysis suggests that the virus enters human cells through the ligation of the spike protein to angiotensin-converting enzyme 2 (ACE(2)). The progression of Covid-19 has been divided into three main stages: stage I-viral response, stage II-pulmonary phase, and stage III-hyperinflammation phase. Once the patients enter stage III, it will likely need ventilation and it becomes difficult to manage. Thus, it will be of paramount importance to find therapies to prevent or slow down the progression of the disease toward stage III. The key event leading to hyperinflammation seems to be the activation of Th-17 immunity response and Cytokine storm. B-2-adrenergic receptors (B(2)ARs) are expressed on airways and on all the immune cells such as macrophages, dendritic cells, B and T lymphocytes. Blocking (B(2)AR) has been proven, also in clinical settings, to reduce Th-17 response and negatively modulate inflammatory cytokines including IL-6 while increasing IFN gamma. Non-selective beta-blockers are currently used to treat several diseases and have been proven to reduce stress-induced inflammation and reduce anxiety. For these reasons, we speculate that targeting B(2)AR in the early phase of Covid-19 might be beneficial to prevent hyperinflammation.

Efficient and reliable synthesis of substituted hydrazinylpyridines in thick-wall ACE tubes via nucleophilic substitution of a chlorine substituent in different chloropyridines is presented. Hydrazine hydrate and alkylhydrazines were used as nucleophiles and simple alcohols and diethyl ether were the only organic solvents necessary, making the process environmentally and user friendly, potentially reaching 100% atomic efficiency. In the next step, transformations of succinic anhydride moieties fused to the bicyclo[2.2.2]octene framework into succinimide moieties via nucleophilic substitution of oxygens were conducted. As nucleophiles two of the synthesized hydrazinylpyridines (2-hydrazinyl-3-nitropyridine and 2-hydrazinyl-5-nitropyridine) and also hydrazine hydrate, phenylhydrazine, and 4-nitrophenylhydrazine were used. Reactions were again carried out in ACE tubes and only simple alcohols, diethyl ether, and acetone were needed as solvents. One of the prepared bicyclo[2.2.2]octene adducts displayed water solubility thus being a promising candidate for future studies as a novel bidentate ligand for various metal cations in aqueous solutions or acting as an unprecedented halogen bond acceptor.