ABSTRACT
Internuclear ophthalmoplegia (INO) is a neuro-ophthalmic disorder caused by damage in the medial longitudinal fasciculus between the third and sixth cranial nerve nuclei. We present a 4-year-old female diagnosed with INO triggered by coronavirus disease 2019 (COVID-19) infection. The patient had history of neonatal meningitis with hydrocephalus without history of surgical intervention. To the best of our knowledge, this is the first case with combined COVID-19 and chronic hydrocephalus as an etiology for INO in a child. COVID-19 may trigger neurological manifestations as INO in susceptible cases.
Subject(s)
COVID-19 , Hydrocephalus , Ocular Motility Disorders , Ophthalmoplegia , COVID-19/complications , Child , Child, Preschool , Female , Humans , Hydrocephalus/complications , Hydrocephalus/diagnosis , Infant, Newborn , Ocular Motility Disorders/diagnosis , Ophthalmoplegia/diagnosisABSTRACT
Researchers are focused on discovering compounds that can interfere with the COVID-19 life cycle. One of the important non-structural proteins is endoribonuclease since it is responsible for processing viral RNA to evade detection of the host defense system. This work investigates a hierarchical structure-based virtual screening approach targeting NSP15. Different filtering approaches to predict the interactions of the compounds have been included in this study. Using a deep learning technique, we screened 823,821 compounds from five different databases (ZINC15, NCI, Drug Bank, Maybridge, and NCI Diversity set III). Subsequently, two docking protocols (extra precision and induced fit) were used to assess the binding affinity of the compounds, followed by molecular dynamic simulation supported by the MM-GBSA free binding energy. Interestingly, one compound (ZINC000104379474) from the ZINC15 database has been found to have a good binding affinity of - 7.68 kcal/Mol. The VERO-E6 cell line was used to investigate its therapeutic effect in vitro. Half-maximal cytotoxic concentration and Inhibitory concentration 50 were determined to be 0.9 mg/ml and 0.01 mg/ml, respectively; therefore, the selectivity index is 90. In conclusion, ZINC000104379474 was shown to be a good hit for targeting the virus that needs further investigations in vivo to be a drug candidate.