De novo generation of dual-target ligands for the treatment of SARS-CoV-2 using deep learning, virtual screening, and molecular dynamic simulations.

De novo generation of molecules with the necessary features offers a promising opportunity for artificial intelligence, such as deep generative approaches. However, creating novel compounds having biological activities toward two distinct targets continues to be a very challenging task. In this study, we develop a unique computational framework for the de novo synthesis of bioactive compounds directed at two predetermined therapeutic targets. This framework is referred to as the dual-target ligand generative network. Our approach uses a stochastic policy to explore chemical spaces called a sequence-based simple molecular input line entry system (SMILES) generator. The steps in the high-level workflow would be to gather and prepare the training data for both targets' molecules, build a neural network model and train it to make molecules, create new molecules using generative AI, and then virtually screen the newly validated molecules against the SARS-CoV-2 PLpro and 3CLpro drug targets. Results shows that novel molecules generated have higher binding affinity with both targets than the conventional drug i.e. Remdesivir being used for the treatment of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Outcomes of SUBGALEAL Drain Placement after two Burr-Holes Craniectomy for Chronic Subdural Hematoma.

OBJECTIVE: To evaluate the efficacy and complications of subgaleal drain placement after two burr-holes evacuation of chronic subdural hematoma (CSDH). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Neurosurgical unit of the Lady Reading Hospital, Peshawar, from April to November 2021. METHODOLOGY: Sixty-four consecutive patients diagnosed with surgically significant unilateral chronic subdural hematoma were prospectively included after obtaining informed consent. All the patients underwent two burr-holes craniectomies and evacuation, followed by subgaleal drain placement. Patient demographics, pre- and postoperative clinical information including hematoma resolution and complications were collected. RESULTS: This study included 44 (69%) males and 20 (31%) females with a mean age of 70.1 ± 8 years. The most common presenting symptoms were headaches (70%) and confusion (68%). Eighteen patients (28%) were taking warfarin or other anticoagulants, whereas, 23 patients (36%) were taking antiplatelet medications at the time of presentation. Thirty-six (56.3%) patients had a history of head trauma. Warfarin use was statistically significant in the patients with no history of head injury. Fifty-five patients (85%) showed no significant recurrence on the 2 week postoperative computed tomography (CT) scan. None of the patients had intraparenchymal hematoma or contusion of iatrogenic origin on postoperative CT scans. CONCLUSION: Subgaleal drain placement after two burr-holes craniectomy led to high-resolution rates. However, no parenchymal injuries were attributed to the procedure. KEY WORDS: Chronic subdural hematoma, Subdural drain, Subperiosteal drain, Burr-hole craniostomy.