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The monkeypox virus (MPXV) is an enveloped, double-stranded DNA virus belonging to the genus Orthopox viruses. In recent years, the virus has spread to countries where it was previously unknown, turning it into a worldwide emergency for public health. This study employs a structural-based drug design approach to identify potential inhibitors for the core cysteine proteinase of MPXV. During the simulations, the study identified two potential inhibitors, compound CHEMBL32926 and compound CHEMBL4861364, demonstrating strong binding affinities and drug-like properties. Their docking scores with the target protein were −10.7 and −10.9 kcal/mol, respectively. This study used ensemble-based protein–ligand docking to account for the binding site conformation variability. By examining how the identified inhibitors interact with the protein, this research sheds light on the workings of the inhibitors’ mechanisms of action. Molecular dynamic simulations of protein–ligand complexes showed fluctuations from the initial docked pose, but they confirmed their binding throughout the simulation. The MMGBSA binding free energy calculations for CHEMBL32926 showed a binding free energy range of (−9.25 to −9.65) kcal/mol, while CHEMBL4861364 exhibited a range of (−41.66 to −31.47) kcal/mol. Later, analogues were searched for these compounds with 70% similarity criteria, and their IC50 was predicted using pre-trained machine learning models. This resulted in identifying two similar compounds for each hit with comparable binding affinity for cysteine proteinase. This study’s structure-based drug design approach provides a promising strategy for identifying new drugs for treating MPXV infections.

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Background: Mercury is used by artisanal — small-scale (ASM) gold miners throughout the World. In 2014, the Sudanese government produced over 60 tons of gold, which make Sudan ranked Africa's third-largest gold miner. Also, Sudan is ranked the 15th global producer. In 2015, over 1 million miners participated in gold mining and extraction. Objective: This study aimed to determine mercury health risk in Sudanese traditional gold mining activities area. Method: This is an analytical cross-sectional observational stud. The studied population was from ALTWAHEN near ABUHAMED. Urine analysis was supported by epidemiological questionnaires designed by (EPI INFO software) following WHO guidelines. Eighty-six respondents completed the questionnaire. The mercury level was determined in 58 urine sample by Petroleum Laboratories Using Direct Mercury Analyzer DMA- 80 instrument. The epidemiological data were analyzed by (EPI INFO). Result: 98% exceed concentration of 100 ug/L which contaminated concentration for occasionally exposed, mean urinary mercury concentration 2785 ug/L, the highest mercury concentration worldwide reported by our study 10250 ug/L, Symptoms in 58 patient showed as Problem finding correct word 46.6%, memory problem 27.6%, problem with thinking clearly 29.3%, nervousness 31%, sadness 46.5%, sexual problem 36.2%, headache 51.7%, excessive salivation 43%, drowsy 48.3%. Conclusion: In this study, the highest urinary mercury concentration was reported (10250 ug/L) compared to other studies. Mercury concentration with no significant difference between the miner groups and others. Also, this study found high incidents of neurological symptoms associated with neurotoxicity. The problem with thinking significantly correlated to the age weighted by mercury concentration. Only tremor significantly related to the time living in the mining area. Otherwise, no significant relationship between mercury concentration ,symptoms and time living in the area. Recommendation: conducting Interventional study by using chelation therapy, Gold miners should use safety tools, Activation of laws and conventions (MINAMATA convention).

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