Your browser doesn't support javascript.
Discovery of natural-derived Mpro inhibitors as therapeutic candidates for COVID-19: Structure-based pharmacophore screening combined with QSAR analysis.
Khanfar, Mohammad A; Salaas, Nada; Abumostafa, Reem.
  • Khanfar MA; College of Pharmacy, Alfaisal University, Al Takhassusi Rd, P. O. Box 50927, Riyadh, 11533, Saudi Arabia.
  • Salaas N; Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, P.O Box 13140, Amman, 11942, Jordan.
  • Abumostafa R; College of Pharmacy, Alfaisal University, Al Takhassusi Rd, P. O. Box 50927, Riyadh, 11533, Saudi Arabia.
Mol Inform ; 42(4): e2200198, 2023 04.
Article in English | MEDLINE | ID: covidwho-2242128
ABSTRACT
The main protease (Mpro ) is an essential enzyme for the life cycle of SARS-CoV-2 and a validated target for treatment of COVID-19 infection. Structure-based pharmacophore modeling combined with QSAR calculations were employed to identify new chemical scaffolds of Mpro inhibitors from natural products repository. Hundreds of pharmacophore models were manually built from their corresponding X-ray crystallographic structures. A pharmacophore model that was validated by receiver operating characteristic (ROC) curve analysis and selected using the statistically optimum QSAR equation was implemented as a 3D-search tool to mine AnalytiCon Discovery database of natural products. Captured hits that showed the highest predicted inhibitory activities were bioassayed. Three active Mpro inhibitors (pseurotin A, lactupicrin, and alpinetin) were successfully identified with IC50 values in low micromolar range.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Biological Products / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Mol Inform Year: 2023 Document Type: Article Affiliation country: Minf.202200198

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Biological Products / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Mol Inform Year: 2023 Document Type: Article Affiliation country: Minf.202200198