Shedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 Mpro Main Protease Inhibitor through Intensive Virtual Screening and In Vitro Evaluation.

The development of specific antiviral therapies targeting SARS-CoV-2 remains fundamental because of the continued high incidence of COVID-19 and limited accessibility to antivirals in some countries. In this context, dark chemical matter (DCM), a set of drug-like compounds with outstanding selectivity profiles that have never shown bioactivity despite being extensively assayed, appears to be an excellent starting point for drug development. Accordingly, in this study, we performed a high-throughput screening to identify inhibitors of the SARS-CoV-2 main protease (Mpro) using DCM compounds as ligands. Multiple receptors and two different docking scoring functions were employed to identify the best molecular docking poses. The selected structures were subjected to extensive conventional and Gaussian accelerated molecular dynamics. From the results, four compounds with the best molecular behavior and binding energy were selected for experimental testing, one of which presented inhibitory activity with a Ki value of 48 ± 5 µM. Through virtual screening, we identified a significant starting point for drug development, shedding new light on DCM compounds.

A complicated trochanteric pressure sore: what is the best surgical management? Case report.

Pressure sores are a common complication after spinal cord injury. But great advances in their management (nursing care, prevention and surgery) have been made in the last four decades. Neglected pressure ulcers may affect the adjacent joint, leading to septic arthritis. We report a paraplegic patient with a large trochanteric sore with hip arthritis, in whom we performed an upper femoral resection and acetabular curettage (Girdlestone's technique) and coverage with the homolateral vastus lateralis muscle flap in one stage. Some questions pertaining to this operation are discussed and there is a comparison with other ways of management described in the literature. We conclude that a successful outcome with the management of such large sores depends on a radical, aggressive operation to remove all of the affected tissue, and ensure a safe coverage with a reliable, viable muscle flap. The collaboration and the positive attitude of the patient towards the procedure and the result obtained are decisive in preventing recurrences.

Gunpowder-related burns.

Gunpowder misuse is a frequent cause of burn injury in our area. The injuries are mostly minor lesions which may be treated on an outpatient basis, the more serious injuries need surgical treatment. Experience of the management of these burns is reported by reviewing 123 clinical charts of patients admitted between 1983 and 1990. The most frequent victims are teenage males who are involved mainly in accidents in the street. The most serious burns followed work-related accidents, with a fatal outcome in 47 per cent of the patients. The serious burns are usually deep dermal or full skin thickness. A common pattern affects groins, genitalia, hypogastrium and hands, and are produced when fireworks ignite in the pockets of the patient's trousers. The management of these lesions does not differ from burns caused by other agents, although attention should be paid to the presence of associated lesions, chiefly to eyes, ears and hands, due to the shockwave and shrapnel.