Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

In-silico Ligand and Structure Based Design of Hiv-1 Protease Inhibitors: Current Trends and Future Directions


Affiliations
1 Department of Pharmacy, MJP Rohilkhand University, Bareilly 243006, Uttar Pradesh, India
2 Department of Applied Chemistry, Faculty of Engineering and Technology, M. J. P. Rohilkhand University, Bareilly - 243006, Uttar Pradesh, India
3 Department of Chemistry, B.S.A. Degree College, Mathura, Uttar Pradesh, India
     

   Subscribe/Renew Journal


A study of the function of the protease inhibitor as well as of highly active antiretroviral therapy is involved in the present work. The paper focused on the cause of drug resistance and related phenomena, the HIV protease structure and its catalytic mechanism, the production of HIV inhibitors based on CADD, as well as ligand-based drug design using QSAR and computational binding energy technique, other computational modelling, optimization based on CORAL software. In order to shed light on the potential growth of the new drug for the treatment of HIV, the debate on the prediction of the desired biological activity and the structural relationship studies and study related to the structure-based drug design and the most potent drugs was reviewed.

Keywords

In-silico Ligand, HIV-1 Protease Inhibitors, Highly Active Anti-Retroviral Therapy (HAART), Support Vector Machine (SVM).
Subscription Login to verify subscription
User
Notifications
Font Size


  • Tomasselli A.G. and Heinrikson R.L. Targeting HIV-protease in AIDS therapy: a current clinical perspective. Biochim Biophys. Acta. 2000; 1477: 189-214.

  • Kempf D.J. Design of symmetry-based, peptidomimetic inhibitors of human immunodeficiency virus protease. Methods Enzymol. 1994; 241: 234-254.

  • Kempf D.J. and Sham H.L. HIV protease inhibitors. Curr. Pharm. Design. 1996; 2: 225-246.

  • Moore M.L. and Dreyer G.B. Substrate based inhibitor of HIV-1 protease. Prospect Drug. Discovery Des. 1993; 1: 85-108.

  • Darwin C. The origin of species by means of natural selection: Or, the preservation of favored races in the struggle for life; John Murray publishers: London. 1859.

  • Richman D.D. HIV drug resistance. Ann Rev. Pharmacol. Toxicol. 1993; 33: 149-164.

  • Peng C, Ho BK, Chang TW, Chang NT. Role of human immunodeficiency virus type 1 specific protease in core protein maturation and viral infectivity. J. Virol. 1989; 63: 2550-2556.

  • Wlodawer A. Miller M. Jaskolski M. Sathyanarayana B.K. Baldwin E. Weber I.T. Selk L.M. Clawson L. Schneider J. Kent S.B. Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science. 1989; 245: 616-621.

  • Wlodawer A. Vondrasek J. Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. Annu. Rev. Biophy. Biomol. Struct. 1998; 27: 249-284.

  • Prabu-Jeyabalan M. Nalivaika E. Schiffer C.A. Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes. Structure. 2002; 10: 369-381.

  • Parkin N.T. Chamorro M. Varmus H.E. Human immunodeficiency virus type 1 gag-pol frameshifting is dependent on downstream mRNA secondary structure: demonstration by expression in-vivo. J. Virol. 1992; 66: 5147-5151.

  • Dunn B.M. Gustchina A. Kay J. Subsite preferences of retroviral proteinases. Methods Enzymol. 1994; 24: 254-278.

  • Tozser J, Weber IT, Gustchina A, Blaha I, Copeland TD, Louis JM, Oroszlan S. Kinetic and modeling studies of S3-S3’ subsites of HIV proteinases. Biochemistry. 1992; 31: 4793-4800.

  • Sangamwar A.T. Deshpande U.D. Pekamwar S.S. Vadwalkar S.M. Improving decision making for drug candidates: A computational approach for benzthiazoles as antifungal. Ind. J. Biotech. 2007; 6: 389-396.

  • Zaihra A. Kumar S.P. Garg V.K. Kumar S. Different Techniques in drug design. Int. J. Ph. Sci. 2010; 2: 623-630.

  • Richard MH. Relations between the biological and physicochemical properties of series of compounds, J. Med. Chem. 1975; 18: 231-233.

  • Erb R.J. Introduction to back propagation neural network computation, Pharm. Res. 1993; 10: 165–170.

  • Friedman S.H. Decamp D.L. Sijbesma R.P. Srdanov G. Wudl F. Kenyon G.L. Inhibition of the HIV-1 Protease by fullerene derivatives: model building studies and experimental verification. J. Am. Chem. Soc. 1993; 115: 6506–6509.

  • Bosi S. Da Ros T. Spalluto G. Balzarini J. Prato M. Synthesis and anti-HIV properties of new water-soluble bisfunctionalized[60] fullerene derivatives Bioorg. Med. Chem. Lett. 2003; 13: 4437–4440.

  • Joy R. A. P. Education to Mothers of Under Fives on First aid Measures for Home Accidents at Nadu Arasur, Coimbatore. Asian J. Nur. Edu. and Research 1(4): Oct-Dec. 2011; Page 125-126.

  • Sijbesma R. Srdanov G. Wudl F. Castoro J.A. Wilkins C. Friedman S.H. De Camp D.L. Kenyon G. Synthesis of a fullerene derivative for the inhibition of HIV enzymes J. Am. Chem. Soc. 1993; 115: 6510–6512.

  • Rajagopalan P. Wudl F. Schinazi R.F. Boudinot F.D. Pharmacokinetics of a water-soluble fullerene in rats. Antimicrob. Agents Chemother. 1996; 40 (10): 2262–2265.

  • Marcorin G.L., Ros T.D. Castellano S. Stefancich G. Bonin-Miertus I.S. Prato M. Design and synthesis of novel [60] fullerene derivatives as potential HIV aspartic protease inhibitors. Org. Lett. 2000; 25: 3955–3958.

  • Bosi S, Da Ros T, Spalluto G, Prato M. Fullerene derivatives: an attractive tool for biological applications. Eur. J. Med. Chem. 2003; 38: 913–923.

  • Marchesan S. Ros T.D. Spalluto G. Balzarinib J. Prato M. Anti-HIV properties of cationic fullerene derivatives. Bioorg. Med. Chem. Lett. 2005; 15: 3615–3618.

  • Mahalwar V. The Companies Act, 2013: Some Reflections. Int. J. Rev. and Res. Social Sci. 1(2): Oct. - Dec. 2013; Page 34-35.

  • Rajeswari U. Venkatesan L., Sonia L. A. Effectiveness of Clinical Pathway for Parturient Mothers upon Knowledge and Practice of Nurses and Maternal Outcome. Asian J. Nur. Edu. and Research 2(2): April-June 2012; Page 90-95.

  • Shubhang S. Distinction between Company and Partnership. Int. J. Rev. and Res. Social Sci. 1(1): July –Sept. 2013; 05-08.

  • Lee V.S. Nimmanpipug P. Aruksakunwong O. Promsri S. Sompornpisut P. Hannongbua S. Structural analysis of lead fullerene-based inhibitor bound to human immunodeficiency virus type 1 protease in solutions from molecular dynamics simulations. J. Mol. Graph. Model. 2007; 26: 558–570.

  • Deepa R. Education on Prevention of Swine Flu among Early Adults in Sri Ramakrishna Arts and Science College, Coimbatore. Asian J. Nur. Edu. and Research 1(1): Jan.-March 2011; Page 01-02

  • Schaal W. Karlsson A. Ahlsen G. Lindberg J. Andersson H.O. Danielson U.H. Classon B. Unge T. Samuelsson B. Hulten J. Hallberg A. Karlen A. Synthesis and Comparative Molecular Field Analysis (CoMFA) of symmetric and nonsymmetric cyclic sufamide HIV-1 protease inhibitors. J. Med. Chem. 2000; 44: 155-169.

  • Paul S. Saha D. Pharmacognostic Studies on Methanolic Extract of the Aerial Part of Leucas zeylanica (L.). Asian J. Pharm. Res. 2(4): Oct. - Dec. 2012; Page 142-143.

  • Sathya Devi K. M. Venkatesan L. Sonia L. Effectiveness of Clinical Pathway for Postnatal Mothers with Vaginal Delivery upon the Knowledge and Practice of Nurses and Maternal Outcome. Asian J. Nur. Edu. and Research 2(3): July-Sept. 2012; Page 165-170.

  • Begum R. N. Dipsomania. Asian J. Nur. Edu. and Research 1(3): July-Sept. 2011; Page 98.

  • Maw H.H. Hall L.H. QSAR modeling of β-lactam binding to human serum proteins. J. Chem. Inf. Comput. Sci. 2002; 42: 290.

  • Kalra P. Reddy T.V. Jayaram B. Free energy component analysis for drug design. J. Med. Chem. 2001; 44: 4325.

  • Pazargadi M. Ashktorab T. Khosravi S. Nursing Students’ Experiences on the Evaluating Role of Their Clinical Educators: a Qualitative Study. Asian J. Nur. Edu. and Research 2(3): July-Sept. 2012; Page 149-153.

  • Huang X. Xu L. Luo X. Fan K. Ji R. Pei G. Chen K. Jiang H. Inhibitory mode of 1,5-diarylpyrazole derivatives against cyclooxygenase-2 and cyclooxygenase-1: molecular docking and 3D QSAR analyses. J. Med. Chem. 2002; 45: 4816-27

  • Prasanna J. L. Deepthi B. Rama Rao N. TSP Based Matrix Tablets: Studying the Effect of Formulation Variables Employing Response Surface Methodology. Asian J. Pharm. Res. 2(3): July-Sept. 2012; Page 120-126.

  • Nair A.C. Jayatilleke P. Wang X. Miertus S. Welsh W.J. Computational studies on tetrahydropyrimidine-2-one HIV-1 protease inhibitors: improving three-dimensional quantitative structure−activity relationship comparative molecular field analysis models by inclusion of calculated inhibitor- and receptor-based properties. J. Med. Chem. 2002; 45: 973.

  • Joy R. A. P. Effect of Foot Reflexology on Pain among Cancer Patients in Oncology Ward, Sri Ramakrishna Hospital, Coimbatore. Asian J. Nur. Edu. and Research 1(4): Oct-Dec. 2011; Page 107-108.


Abstract Views: 329

PDF Views: 0




  • In-silico Ligand and Structure Based Design of Hiv-1 Protease Inhibitors: Current Trends and Future Directions

Abstract Views: 329  |  PDF Views: 0

Authors

S. Ramasamy
Department of Pharmacy, MJP Rohilkhand University, Bareilly 243006, Uttar Pradesh, India
Sushmita Gupta
Department of Applied Chemistry, Faculty of Engineering and Technology, M. J. P. Rohilkhand University, Bareilly - 243006, Uttar Pradesh, India
Ritu Rani Chaudhary
Department of Chemistry, B.S.A. Degree College, Mathura, Uttar Pradesh, India
Amit Kumar Verma
Department of Pharmacy, MJP Rohilkhand University, Bareilly 243006, Uttar Pradesh, India

Abstract


A study of the function of the protease inhibitor as well as of highly active antiretroviral therapy is involved in the present work. The paper focused on the cause of drug resistance and related phenomena, the HIV protease structure and its catalytic mechanism, the production of HIV inhibitors based on CADD, as well as ligand-based drug design using QSAR and computational binding energy technique, other computational modelling, optimization based on CORAL software. In order to shed light on the potential growth of the new drug for the treatment of HIV, the debate on the prediction of the desired biological activity and the structural relationship studies and study related to the structure-based drug design and the most potent drugs was reviewed.

Keywords


In-silico Ligand, HIV-1 Protease Inhibitors, Highly Active Anti-Retroviral Therapy (HAART), Support Vector Machine (SVM).

References