Chandrabhan Seniya1,2, Shilpi Shrivastava1, Sanjay Kumar Singh3, Ghulam Jilani Khan4. 1. Department of Biotechnology, Madhav Institute of Technology and Science, Race Course Road, Gola Ka Mandir, Gwalior (M.P.) India. 2. School of Engineering, The University of Warwick, Coventry, CV4 7AL, UK. 3. Bose Institute, 93/1, A.P.C. Road, Kolkata 700009, India. 4. Seed ProFarm India Pvt. Ltd, 9 Anthem, Gundala Pochampally Village, Secunderabad-500014, Andhra Pradesh, India.
Abstract
OBJECTIVE: To find new bioactive molecules for the treatment of swine flu. METHODS: The present study is an attempt to elucidate inhibition potential of andrographolide and its derivatives along with an associated binding mechanism through virtual screening and molecular docking simulation studies. RESULTS: Our findings revealed structural conformation changes in 150 loop, secondary sialic acid binding site residues of ACZ97474 {Neuraminidase (A/Blore/NIV236/2009(H1N1)}. Andrographolide have been identified as the highest binging energy of -10.88 Kcal/mol, 3 hydrogen bond interactions (Arg152, Lys150, and Gly197), total intermolecular energy of -12.07 Kcal/mol with bioactivity value (Ki) of 10.59 nmol/L, while the Food and Drug Admistraton approved drug Oseltamivir and Zanamivir have shown 2 and 4 hydrogen bond interactions with binding energies of -6.28 Kcal/mol and -7.73Kcal/mol, respectively, which is higher than andrographolide. The guanidine group of Arg152 has binding affinities to the hydrophilic nature of the inhibitors (-OH and =O groups), as identified by docking of andrographolide (CID: 5318517) on neuraminidase. CONCLUSIONS: Hence, andrographolide has the potential to inhibit neuraminidase activity of H1N1 and may be used as an alternative medicinal therapy for swine flu positive patient. With potent antiviral activity and a potentially new mechanism of action, andrographolide may warrant further evaluation as a possible therapy for influenza.
OBJECTIVE: To find new bioactive molecules for the treatment of swine flu. METHODS: The present study is an attempt to elucidate inhibition potential of andrographolide and its derivatives along with an associated binding mechanism through virtual screening and molecular docking simulation studies. RESULTS: Our findings revealed structural conformation changes in 150 loop, secondary sialic acid binding site residues of ACZ97474 {Neuraminidase (A/Blore/NIV236/2009(H1N1)}. Andrographolide have been identified as the highest binging energy of -10.88 Kcal/mol, 3 hydrogen bond interactions (Arg152, Lys150, and Gly197), total intermolecular energy of -12.07 Kcal/mol with bioactivity value (Ki) of 10.59 nmol/L, while the Food and Drug Admistraton approved drug Oseltamivir and Zanamivir have shown 2 and 4 hydrogen bond interactions with binding energies of -6.28 Kcal/mol and -7.73Kcal/mol, respectively, which is higher than andrographolide. The guanidine group of Arg152 has binding affinities to the hydrophilic nature of the inhibitors (-OH and =O groups), as identified by docking of andrographolide (CID: 5318517) on neuraminidase. CONCLUSIONS: Hence, andrographolide has the potential to inhibit neuraminidase activity of H1N1 and may be used as an alternative medicinal therapy for swine flu positive patient. With potent antiviral activity and a potentially new mechanism of action, andrographolide may warrant further evaluation as a possible therapy for influenza.
Authors: Narayanan Eswar; Bino John; Nebojsa Mirkovic; Andras Fiser; Valentin A Ilyin; Ursula Pieper; Ashley C Stuart; Marc A Marti-Renom; M S Madhusudhan; Bozidar Yerkovich; Andrej Sali Journal: Nucleic Acids Res Date: 2003-07-01 Impact factor: 16.971