Dietary stigmastane-type saponins as promising dual-target directed inhibitors of SARS-CoV-2 proteases: a structure-based screening
| Autor: | Oludare M. Ogunyemi, Charles O. Olaiya, Joseph O. Adebayo, Ibrahim M. Ibrahim, Modupe M. Fabusiwa, Joshua O. Ocheje, Gideon A. Gyebi |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Proteases Protease biology medicine.drug_class Chemistry General Chemical Engineering medicine.medical_treatment media_common.quotation_subject In silico Vernonia amygdalina General Chemistry biology.organism_classification Nutraceutical Docking (dog) Biochemistry medicine Antiviral drug media_common |
| Zdroj: | RSC advances. 11(53) |
| ISSN: | 2046-2069 |
| Popis: | Despite the development of COVID-19 vaccines, at present, there is still no approved antiviral drug against the pandemic. The SARS-CoV-2 3-chymotrypsin-like proteases (S-3CLpro) and papain-like protease (S-PLpro) are essential for the viral proliferation cycle, hence attractive drug targets. Plant-based dietary components that have been extensively reported for antiviral activities may serve as cheap sources of preventive nutraceuticals and/or antiviral drugs. A custom-made library of 176 phytochemicals from five West African antiviral culinary herbs was screened for potential dual-target-directed inhibitors of S-3CLpro and S-PLpro in silico. The docking analysis revealed fifteen steroidal saponins (FSS) from Vernonia amygdalina with the highest binding tendency for the active sites of S-3CLpro and S-PLpro. In an optimized docking analysis, the FSS were further docked against four equilibrated conformers of the S-3CLpro and S-PLpro. Three stigmastane-type steroidal saponins (vernonioside A2, vernonioside A4 and vernonioside D2) were revealed as the lead compounds. These compounds interacted with the catalytic residues of both S-3CLpro and S-PLpro, thereby exhibiting dual inhibitory potential against these SARS-CoV-2 cysteine proteases. The binding free energy calculations further corroborated the static and optimized docking analysis. The complexed proteases with these promising phytochemicals were stable during a full atomistic MD simulation while the phytochemicals exhibited favourable physicochemical and ADMET properties, hence, recommended as promising inhibitors of SARS-CoV-2 cysteine proteases. |
| Databáze: | OpenAIRE |
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