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In a search for potential drug candidates for combating COVID-19: computational study revealed salvianolic acid B as a potential therapeutic targeting 3CLpro and spike proteins

Ayman Abo Elmaaty, Khaled M. Darwish, Muhammad Khattab, Sameh S. Elhady, Mohammed Salah, Mohammed I. A. Hamed, Ahmed A. Al‐Karmalawy, Moustafa M. Saleh

2021Journal of Biomolecular Structure and Dynamics74 citationsDOIOpen Access PDF

Abstract

showed promising binding affinities against the two specified SARS-CoV-2 target proteins compared to the reference standards used. Hence molecular dynamics simulations followed by calculating the free-binding energy were carried out for Sal-B providing information on its affinity, stability, and thermodynamic behavior within the two SARS-CoV-2 target proteins as well as key ligand-protein binding aspects. Besides, the quantum mechanical calculations showed that Sal-B can adopt different conformations due to the existence of various rotatable bonds. Therefore, the enhanced antiviral activity of Sal-B among other studied compounds can be also attributed to the structural flexibility of Sal-B. Our study gives an explanation of the structure activity relationship required for targeting SARS-CoV-2 3CLpro and Spike proteins and also facilitates the future design and synthesis of new potential drugs exhibiting better affinity and specificity. Besides, an ADME study was carried out on screened compounds and reference controls revealing their pharmacokinetics properties.Communicated by Ramaswamy H. Sarma.

Topics & Concepts

In silicoDrug repositioningChemistryDrug discoveryDrugComputational biologyDocking (animal)Binding affinitiesBiochemistryTarget proteinPharmacologyBiologyMedicineGeneReceptorNursingPharmacological Effects of Natural CompoundsComputational Drug Discovery MethodsPlant-based Medicinal Research