Design,synthesis and docking study of Vortioxetine derivatives as a SARS-CoV-2 main protease inhibitor

PurposeVortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2.MethodsIn this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (M^pro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper.ResultsBased on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards M^pro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 M^pro) and vortioxetine.ConclusionThis study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-022-00441-z.     

Structural elucidation of NASICON (Na3Al2P3O12) based glass electrolyte materials: effective influence of boron and gallium

Understanding the conductivity variations induced by compositional changes in sodium super ionic conducting (NASICON) glass materials is highly relevant for applications such as solid electrolytes for sodium (Na) ion batteries. In the research reported in this paper, NASICON-based NCAP glass (Na_2.8Ca_0.1Al₂P₃O₁₂) was selected as the parent glass. The present study demonstrates the changes in the Na⁺ ion conductivity of NCAP bulk glass with the substitution of boron (NCABP: Na_2.8Ca_0.1Al₂B_0.5P_2.7O₁₂) and gallium (NCAGP: Na_2.8Ca_0.1Al₂Ga_0.5P_2.7O₁₂) for phosphorus and the resulting structural variations found in the glass network. For a detailed structural analysis of NCAP, NCABP and NCAGP glasses, micro-Raman and magic angle spinning-nuclear magnetic resonance (MAS-NMR) spectroscopic techniques (for ³¹P, ²⁷Al, ²³Na, ¹¹B and ⁷¹Ga nuclei) were used. The Raman spectrum revealed that the NCAP glass structure is more analogous to the AlPO₄ mesoporous glass structure. The ³¹P MAS-NMR spectrum illustrated that the NCAP glass structure consists of a high concentration of Q⁰ (3Al) units, followed by Q⁰ (2Al) units. The ²⁷Al MAS-NMR spectrum indicates that alumina exists at five different sites, which include AlO₄ units surrounded by AlO₆ units, Al(OP)₄, Al(OP)₅, Al(OAl)₆ and Al(OP)₆, in the NCAP glass structure. The ³¹P, ²⁷Al and ¹¹B MAS-NMR spectra of the NCABP glass revealed the absence of B–O–Al linkages and the presence of B₃–O–B₄–O–P₄ linkages which further leads to the formation of borate and borophosphate domains. The ⁷¹Ga MAS-NMR spectrum suggests that gallium cations in the NCAGP glass compete with the alumina cations and occupy four (GaO₄), five (GaO₅) and six (GaO₆) coordinated sites. The Raman spectrum of NCAGP glass indicates that sodium cations have also been substituted by gallium cations in the NCAP glass structure. From impedance analysis, the dc conductivity of the NCAP glass (∼3.13 × 10⁻⁸ S cm⁻¹) is slightly decreased with the substitution of gallium (∼2.27 × 10⁻⁸ S cm⁻¹) but considerably decreased with the substitution of boron (∼1.46 × 10⁻⁸ S cm⁻¹). The variation in the conductivity values are described based on the structural changes of NCAP glass with the substitution of gallium and boron.

Understanding the conductivity variations induced by compositional changes in sodium super ionic conducting (NASICON) glass materials is highly relevant for applications such as solid electrolytes for sodium (Na) ion batteries.     

Extra-Aortic Mycotic Aneurysm Due to Group A Streptococcus after Pharyngitis

Mycotic aneurysms, especially outside the aorta, are uncommon, with group A Streptococcus a particularly rare cause. We report a case of extra-aortic mycotic aneurysm following a sore throat without demonstrable bacteremia where identification of the pathological organism was made by molecular diagnostic techniques after a standard laboratory culture was negative.     

Outcome of humeral shaft fractures treated by functional cast brace

Background:Functional brace application for isolated humeral shaft fracture persistently yields good results. Nonunion though uncommon involves usually the proximal third shaft fractures. Instead of polyethylene bivalve functional brace four plaster sleeves wrapped and molded with little more proximal extension expected to prevent nonunion of proximal third fractures. Periodic compressibility of the cast is likely to yield a better result. This can be applied on the 1^st day of the presentation as an outpatient basis. Comprehensive objective scoring system befitting for fracture humeral shaft is a need.Results:The results were assessed using 100 point scoring system where union allotted 30 points and 60 points allotted for angulations (10), elbow motion (10), shoulder abduction (10), shortening (5), rotation (5), absence of infection (10), absence of nerve palsy during treatment (10). Remaining 10 points were allotted for five items with two points each. They were the absence of skin sore, absence of vascular problem, absence of reflex sympathetic dystrophy (RSD), recovery of paralyzed nerve during injury and recovery of paralyzed nerve during treatment. Results were considered excellent with 90 and above, good with 80–89, fair with 70–79 and poor below 70 point. Results at 6 months were excellent in 43.94% (n = 29), good in 42.42% (n = 28), fair in 9.1% (n = 6), poor in 4.55% (n = 3). Union took place in 98.48% (n = 65) with an average of 10.3 weeks (range 6–16 weeks). 87.5% (n = 7) paralyzed radial nerve recovered. All wounds healed. Four patients had transient skin problem. One patient with mid shaft fracture had nonunion due to the muscle interposition.Conclusion:Modified functional cast brace is one of the options in treatment for humeral shaft fractures as it can be applied on the 1^st day of the presentation in most of the situations. Simple objective scoring system was useful particularly in uneducated patients.