Your browser doesn't support javascript.
Exploiting the co-crystal ligands shape, features and structure-based approaches for identification of SARS-CoV-2 Mpro inhibitors.
Yousaf, Numan; Jabeen, Yaruq; Imran, Muhammad; Saleem, Muhammad; Rahman, Moazur; Maqbool, Abbas; Iqbal, Mazhar; Muddassar, Muhammad.
  • Yousaf N; Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
  • Jabeen Y; Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
  • Imran M; KAM School of Life Sciences, Forman Christian College, Lahore, Pakistan.
  • Saleem M; School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
  • Rahman M; School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
  • Maqbool A; Department of Biochemistry and Metabolism John Innes Centre, Norwich Research Park, Norwich, UK.
  • Iqbal M; Health Biotechnology Division, National Institute for Biotechnology & Genetic Engineering (NIBGE), Faisalabad, Pakistan.
  • Muddassar M; Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
J Biomol Struct Dyn ; : 1-14, 2023 Mar 22.
Article in English | MEDLINE | ID: covidwho-2287998
ABSTRACT
SARS-CoV-2 enters the host cell through the ACE2 receptor and replicates its genome using an RNA-Dependent RNA Polymerase (RDRP). The functional RDRP is released from pro-protein pp1ab by the proteolytic activity of Main protease (Mpro) which is encoded within the viral genome. Due to its vital role in proteolysis of viral polyprotein chains, it has become an attractive potential drug target. We employed a hierarchical virtual screening approach to identify small synthetic protease inhibitors. Statistically optimized molecular shape and color-based features (various functional groups) from co-crystal ligands were used to screen different databases through various scoring schemes. Then, the electrostatic complementarity of screened compounds was matched with the most active molecule to further reduce the hit molecules' size. Finally, five hundred eighty-seven molecules were docked in Mpro catalytic binding site, out of which 29 common best hits were selected based on Glide and FRED scores. Five best-fitting compounds in complex with Mpro were subjected to MD simulations to analyze their structural stability and binding affinities with Mpro using MM/GB(PB)SA models. Modeling results suggest that identified hits can act as the lead compounds for designing better active Mpro inhibitors to enhance the chemical space to combat COVID-19.Communicated by Ramaswamy H. Sarma.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal: J Biomol Struct Dyn Year: 2023 Document Type: Article Affiliation country: 07391102.2023.2189478

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal: J Biomol Struct Dyn Year: 2023 Document Type: Article Affiliation country: 07391102.2023.2189478