Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity.

Autor: Alkafaas SS; Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt. samar.alkafas@science.tanta.edu.eg., Abdallah AM; Narcotic Research Department, National Center for Social and Criminological Research (NCSCR), Giza, 11561, Egypt., Hassan MH; Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt., Hussien AM; Biotechnology department at Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt., Elkafas SS; Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University, Menofia, Egypt.; Faculty of Control System and Robotics, ITMO University, Saint-Petersburg, 197101, Russia., Loutfy SA; Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.; Nanotechnology Research Center, British University, Cairo, Egypt., Mikhail A; Department of Physics, Faculty of Science, Minia University, Minia, Egypt.; Faculty of Physics, ITMO University, Saint Petersburg, Russia., Murad OG; Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt., Elsalahaty MI; Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt., Hessien M; Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt., Elshazli RM; Biochemistry and Molecular Genetics Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University - Egypt, New Damietta, 34517, Egypt., Alsaeed FA; Department of Biology, College of Science, King Khalid University, Muhayl, Saudi Arabia., Ahmed AE; Biology Department, College of Science, King Khalid University, Abha, 61413, Saudi Arabia., Kamal HK; Anatomy and Histology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Hafez W; NMC Royal Hospital, 16Th Street, 35233, Khalifa City, Abu Dhabi, United Arab Emirates.; Medical Research Division, Department of Internal Medicine, The National Research Centre, 12622, 33 El Buhouth St, Ad Doqi, Dokki, Cairo Governorate, Egypt., El-Saadony MT; Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt., El-Tarabily KA; Department of Biology, College of Science, United Arab Emirates University, Al-Ain, 15551, United Arab Emirates., Ghosh S; Department of Genetics, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, 9301, South Africa.; Natural & Medical Science Research Center, University of Nizwa, Nizwa, Oman.
Jazyk: angličtina
Zdroj: BMC public health [BMC Public Health] 2024 Feb 06; Vol. 24 (1), pp. 395. Date of Electronic Publication: 2024 Feb 06.
DOI: 10.1186/s12889-024-17747-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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