Attacking the SARS-CoV-2 Replication Machinery with the Pathogen Box's Molecules

Introduction: The world is currently facing a pandemic initiated by the new coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. Viral transcription and replication are the fundamental processes of any virus. They allow the synthesis of genetic material and the consequent multiplication of the virus to infect other cells or organisms.Methods: The most important protein in SARS-CoV-2 is the RNA polymerase (RdRp or nsp12), responsible for both processes. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for a drug search, like virtual screening and molecular docking. Here, the Pathogen Box database of chemical compounds was used together with Remdesivir, Beclabuvir, and Sofosbuvir drugs as potential inhibitors of nsp12.Results: The results showed Top10 potential target inhibitors with binding energy (ΔG) higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with ΔG = −7.53 kcal/mol, present interactions with three important residues of the nsp12 catalytic site.Conclusion: These proposed ligands would be used for subsequent validation by molecular dynamics, where they can be considered as drugs for the development of effective treatments against this new pandemic.

JEJUNAL PERFORATION SECONDARY TO KICK DURING KICK-BOXING PRACTICE: LAPAROSCOPIC MANAGEMENT

Small bowel injury in a sports setting is a rare occurrence with a paucity of reported cases. A 30-year old male patient consulted for generalized abdominal pain subsequent to secondary blunt abdominal trauma during kick-boxing practice. A computed tomography scan of the abdomen and pelvis revealed a moderate amount of free fluid in both the parietocolic space and the rectovesical pouch, with perihepatic pneumoperitoneum. Emergency laparoscopy was indicated and a closure of small bowel defect was performed. Diagnosis of small bowel injuries is difficult, resulting in delayed treatment and increased mortality and morbidity.

Recommendations for the teams that manage school canteens in the public health emergency of COVID-19 in Argentina

The impact of the pandemic caused by COVID-19 may deepen the situations of malnutrition, where it will be necessary to adapt food programs to this new context. The objective of this work was to present the methodology and the main results of the process of formulating a federal guide based on scientific evidence and adapted to the reality of the child and adolescent population that attend school canteens in the 24 jurisdictions of Argentina. It was observed that the modalities for the implementation of SC during the pandemic were: food modules (the most frequent);food modules delivered at school with regular SC support and, food and/or snacks delivered daily. There was little evidence at the global and regional level on specific recommendations applied to the implementation of SC, although recommendations on hygiene and food handling were found. Based on a participatory process among key actors, specific recommendations were obtained according to the dimensions of food and nutrition security (FNS). It is concluded that it is necessary to increase participatory experiences in the design of recommendations based on evidence, adapted to the territory and that assume a comprehensive approach from the dimensions of FNS. Arch Latinoam Nutr 2020;70(3): 215-234. © 2020 Archivos Latinoamericanos Nutricion. All rights reserved.

Attacking the SARS-CoV-2 Replication Machinery with the Pathogen Box’s Molecules (preprint)

The world is currently facing a pandemic caused by the new 2019 coronavirus disease (COVID-19), caused by SARS-CoV-2. Among the fundamental processes of this virus are viral transcription and replication. They allow the synthesisof genetic material and the consequent multiplication of the virus to infect other cells or organisms. These are performed by a multi-subunit machinery of various nonstructural proteins (nsp); among which the RNA-dependent RNApolymerase (RdRp or nsp12) is the most important, and, at the same time, conserved among coronaviruses. The structure of this protein (PDB ID: 6M71) was used as a target in the application of computational strategies for drugsearch, like virtual screening and molecular docking. The region considered for virtual screening has three important amino acids for protein catalysis: T680 (located in Motif A), N691 and D623 (located in Motif B), where a grid box was located. In turn, applying the concept of drug repositioning isconsidered as a quick response in the treatment of sudden outbreaks of diseases. Here, we used the Pathogen Box, a database of chemical compounds analyzed for the treatment against malaria, which were filtered under the criteria of selecting those that do not present any violation of Lipinski'sRule of Five. At the same time, the Remdesivir, Beclabuvir and Sofosbuvir drug, previously used in in silico and clinical studies for inhibition of nsp12, were used as positive controls. The results showed a Top10 potential target inhibitors, with binding energy higher than those of the positive controls, of which TCMDC-134153 and TCMDC-135052, both with -7.53 kcal/mol, present interactions with the three important residues of the nsp12 catalytic site. These proposed ligands would be used for subsequent validation by molecular dynamics, where they can beconsidered as drugs for the development of effective treatments against this new pandemic.