A density functional theory study on silver and bis-silver complexes with lighter tetrylene: are silver and bis-silver carbenes candidates for SARS-CoV-2 inhibition? Insight from molecular docking simulation

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE_Ph–AgCl and (NHE_Ph–AgCl)₂ with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver–tetrylene complexes (NHE–Ag) and bis-silver–tetrylene complexes (NHE–Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC–Ag and NHC–Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl)₂, whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE–Ag bond in the complex families follows the order of NHC–Ag > NHSi–Ag > NHGe–Ag and NHSi–Ag-bis > NHGe–Ag-bis > NHC–Ag-bis. The natural bond orbital analysis implies that the [NHE_Ph→AgCl] and [(NHE_Ph)₂→(AgCl)₂] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver–carbene NHC–Ag, bis-silver–carbene NHC–Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from −17.5 to −16.5 kcal mol⁻¹ and −16.9 to −16.6 kcal mol⁻¹, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver–carbene NHC–Ag and bis-silver–carbene NHC–Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.

Simultaneous inhibition of silver–carbene complexes to ACE2 and PDB6LU7 is conducive for the prevention of SARS-CoV-2 infection: a virtual prediction.     

Percutaneous embolisation of a iatrogenic fistula between the internal mammary artery and the coronary vein

Latrogenic fistula between the aorta and coronary vein is a rare complication of coronary bypass surgery due to accidental venous or arterial graft onto a coronary vein. The authors report a case of a patient admitted to hospital 2 months after coronary bypass surgery for cardiac failure due to a iatrogenic fistula by implantation of the left internal mammary artery on the great coronary vein. This presentation led to the choice of percutaneous embolisation of the fistula by the release of 6 coils. Based on a review of the literature, this clinical case illustrates the feasibility and value of percutaneous embolisation of iatrogenic fistulae.     

An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent

A mild and highly efficient reaction for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetically supported Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP) has been developed via one-pot multicomponent processes under solvent-free sonication. These reactions have good to excellent yields, mild conditions, and work-up simplicity. This method represents a new method for the preparation of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. More importantly, LADES@MNP can be easily recovered by magnetic separation and reused five times without significant loss of catalytic activity.

A mild and highly efficient method for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP).     

Combined administration of microdoses of growth hormone and erythropoietin: Effects on performance and evaluation of GH detection capability using anti‐doping methods

The combination of growth hormone (GH) and recombinant erythropoietin (rEPO) is thought to be used particularly in endurance sports. Our objective was to reproduce a 2‐week administration of rEPO microdoses alone or in combination with GH microdoses (three times a week) on healthy and athletic male subjects and to evaluate if GH had any additional effects compared to EPO treatment alone. The effects of the treatments on hematological parameters and VO2max were studied as well as the detection of GH in serum. While the rEPO microdose regimen was associated with a significant increase in reticulocytes, no clear elevation in hemoglobin concentration (HGB) was observed. Using a correction by plasma volume did not reveal more effects of EPO on HGB. Our results did not show any additional effect when the GH microdoses were co‐administered. In addition, no clear increase in VO2max was observed after treatment, with an elevation in only half the subjects in both groups (EPO and EPO+GH). A clear effect of GH on insulin‐like growth factor I (IGF‐I) was seen but it was lower on procollagen III amino‐terminal propeptide (P‐III‐NP). GH detection using the direct isoform test identified only one subject 24 hours after receiving GH. The GH biomarker test combining IGF‐I and P‐III‐NP was not able to detect the GH administration. However, a longitudinal follow‐up of the intraindividual variations showed a significant increase in IGF‐I 24 and 48 hours after GH administration in most subjects, while the effect of GH microdoses on P‐III‐NP was less straightforward.