Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity
Samar Sami Alkafaas, Abanoub Mosaad Abdallah, Mai H Hassan, Aya Misbah Hussien, Sara Samy Elkafas, Samah A Loutfy, Abanoub Mikhail, Omnia G Murad, Mohamed I Elsalahaty, Mohamed Hessien, Rami M Elshazli, Fatimah A Alsaeed, Ahmed Ezzat Ahmed, Hani K Kamal, Wael Hafez, Mohamed T El-Saadony, Khaled A El-Tarabily, Soumya Ghosh
BMC Public Health, doi:10.1186/s12889-024-17747-z
Recently, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, caused > 6 million deaths. Symptoms included respiratory strain and complications, leading to severe pneumonia. SARS-CoV-2 attaches to the ACE-2 receptor of the host cell membrane to enter. Targeting the SARS-CoV-2 entry may effectively inhibit infection. Acid sphingomyelinase (ASMase) is a lysosomal protein that catalyzes the conversion of sphingolipid (sphingomyelin) to ceramide. Ceramide molecules aggregate/assemble on the plasma membrane to form "platforms" that facilitate the viral intake into the cell. Impairing the ASMase activity will eventually disrupt viral entry into the cell. In this review, we identified the metabolism of sphingolipids, sphingolipids' role in cell signal transduction cascades, and viral infection mechanisms. Also, we outlined ASMase structure and underlying mechanisms inhibiting viral entry 40 with the aid of inhibitors of acid sphingomyelinase (FIASMAs). In silico molecular docking analyses of FIASMAs with inhibitors revealed that dilazep (S = -12.58 kcal/mol), emetine (S = -11.65 kcal/ mol), pimozide (S = -11.29 kcal/mol), carvedilol (S = -11.28 kcal/mol), mebeverine (S = -11.14 kcal/mol), cepharanthine (S = -11.06 kcal/mol), hydroxyzin (S = -10.96 kcal/mol), astemizole (S = -10.81 kcal/mol), sertindole (S = -10.55 kcal/mol), and bepridil (S = -10.47 kcal/mol) have higher inhibition activity than the candidate drug amiodarone (S = -10.43 kcal/mol), making them better options for inhibition.
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