publication . Article . 2008

Molecular dynamic simulations analysis of ritronavir and lopinavir as SARS-CoV 3CLpro inhibitors

Veena Nukoolkarn; Vannajan Sanghiran Lee; Maturos Malaisree; Ornjira Aruksakulwong; Supot Hannongbua;
Open Access English
  • Published: 30 Jul 2008 Journal: Journal of Theoretical Biology, volume 254, issue 4, pages 861-867 (issn: 0022-5193, eissn: 1095-8541, Copyright policy)
  • Publisher: Elsevier Ltd.
Abstract
Since the emergence of the severe acute respiratory syndrome (SARS) to date, neither an effective antiviral drug nor a vaccine against SARS is available. However, it was found that a mixture of two HIV-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the SARS virus. To understand the fine details of the molecular interactions between these proteinase inhibitors and the SARS virus via complexation, molecular dynamics simulations were carried out for the SARS-CoV 3CL(pro) free enzyme (free SARS) and its complexes with lopinavir (SARS-LPV) and ritonavir (SARS-RTV). The results show that flap closing was clearly observe...
Persistent Identifiers
Subjects
Medical Subject Headings: skin and connective tissue diseasesfungibody regionsvirus diseasesviruses
free text keywords: Article, SARS, Proteinase, MD simulations, Ritonavir, Lopinavir, General Biochemistry, Genetics and Molecular Biology, Modelling and Simulation, Statistics and Probability, General Immunology and Microbiology, Applied Mathematics, General Agricultural and Biological Sciences, General Medicine, Plasma protein binding, Virology, Antiviral drug, medicine.drug_class, medicine, Lopinavir, medicine.drug, Molecular interactions, Molecular dynamics, Active site, biology.protein, biology, Enzyme, chemistry.chemical_classification, chemistry, Ritonavir
25 references, page 1 of 2

Anand, K., Palm, G.J., Mesters, J.R., Siddell, S.G., Ziebuhr, J., Hilgenfeld, R.. Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an a-extra helical domain. EMBO J.. 2002; 21: 3213-3224 [OpenAIRE] [PubMed]

Anand, K., Ziebuhr, J., Wadhwani, P., Mesters, J.R., Hilgenfeld, R.. Coronavirus main protease (3CLpro) structure: basis for design of anti-SARS drugs. Science. 2003; 300: 1763-1767 [OpenAIRE] [PubMed]

Carlson, H.A.. Protein flexibility and drug design: how to hit a moving target. Curr. Opin. Chem. Biol.. 2002; 6: 447-452 [PubMed]

Carlson, H.A., McCammon, J.A.. Accommodating protein flexibility in computational drug design. Mol. Pharmacol.. 2000; 57: 213-218 [PubMed]

Case, D.A., Pearlman, J.W., Caldwell, T.E., Cheatham, J., Wang, W.S., Ross, C.L., Simmerling, T.A., Darden, K.M., Merz, R.V., Stanton, A.L., Cheng, J.J., Vincent, M., Crowley, V., Tsui, H., Gohlke, R.J., Radmer, Y., Duan, J., Pitera, I., Massova, G.L., Seibel, U.C., Singh, P.K., Kollman, P.A.. 2002

Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz, K.M., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W., Kollman, P.A.. A second generation force-field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc.. 1995; 117: 5179-5197

Donnelly, C.A., Ghani, A.C., Leung, G.M., Hedley, A.J., Fraser, C., Riley, S., Abu-Raddad, L.J., Ho, L.-M., Thach, T.-Q., Chau, P., Chan, K.-P., Lam, T.-H., Tse, L.-Y., Tsang, T., Liu, S.-H., Kong, J.H.B., Lau, E.M.C., Ferguson, N.M., Anderson, R.M.. Epidermiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003; 361: 1761-1766 [OpenAIRE] [PubMed]

Hornak, V., Okur, A., Rizzo, R.C., Simmerling, C.. HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations. Proc. Natl. Acad. Sci. USA. 2006; 103: 915-920 [OpenAIRE] [PubMed]

Hornak, V., Okur, A., Rizzo, R.C., Simmerling, C.. HIV-1 protease flaps spontaneously close to the correct structure in simulations following manual placement of an inhibitor into the open state. J. Am. Chem. Soc.. 2006; 128: 2812-2813 [OpenAIRE] [PubMed]

Hsu, M.-F., Kuo, C.-J., Chang, K.-T., Chang, H.-C., Chou, C.-C., Ko, T.-P., Shr, H.-L., Chang, G.-G., Wang, A.H.J., Liang, P.-H.. Mechanism of the maturation process of SARS-CoV 3CL protease. J. Biol. Chem.. 2005; 280: 31257-31266 [OpenAIRE] [PubMed]

Huang, C., Wei, P., Fan, K., Liu, Y., Lai, L.. 3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism. Biochemistry. 2004; 43: 4568-4574 [PubMed]

Jenwitheesuk, E., Samudrala, R.. Identifying inhibitors of the SARS coronavirus proteinase. Bioorg. Med. Chem. Lett.. 2003; 13: 3989-3992 [OpenAIRE] [PubMed]

Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., Klein, M.L.. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys.. 1983; 79: 926-935

Kuiken, T., Fouchier, R.A.M., Schutten, M., Rimmelzwaan, G.F., van Amerongen, G., van Riel, D., Laman, J.D., de Jong, T., van Doornum, G., Lim, W., Ling, A.E., Chan, P.K.S., Tam, J.S., Zambon, M.C., Gopal, R., Drosten, C., van der Werf, S., Escriou, N., Manuguerra, J.-C., Stöhr, K., Peiris, J.S.M., Osterhaus, A.D.M.E.. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003; 362: 263-270 [OpenAIRE] [PubMed]

Lee, T.W., Cherney, M.M., Huitema, C., Liu, J., James, K.E., Powers, J.C., Eltis, L.D., James, M.N.G.. Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like aza-peptide epoxide. J. Mol. Biol.. 2005; 353: 1137-1151 [OpenAIRE] [PubMed]

25 references, page 1 of 2
Abstract
Since the emergence of the severe acute respiratory syndrome (SARS) to date, neither an effective antiviral drug nor a vaccine against SARS is available. However, it was found that a mixture of two HIV-1 proteinase inhibitors, lopinavir and ritonavir, exhibited some signs of effectiveness against the SARS virus. To understand the fine details of the molecular interactions between these proteinase inhibitors and the SARS virus via complexation, molecular dynamics simulations were carried out for the SARS-CoV 3CL(pro) free enzyme (free SARS) and its complexes with lopinavir (SARS-LPV) and ritonavir (SARS-RTV). The results show that flap closing was clearly observe...
Persistent Identifiers
Subjects
Medical Subject Headings: skin and connective tissue diseasesfungibody regionsvirus diseasesviruses
free text keywords: Article, SARS, Proteinase, MD simulations, Ritonavir, Lopinavir, General Biochemistry, Genetics and Molecular Biology, Modelling and Simulation, Statistics and Probability, General Immunology and Microbiology, Applied Mathematics, General Agricultural and Biological Sciences, General Medicine, Plasma protein binding, Virology, Antiviral drug, medicine.drug_class, medicine, Lopinavir, medicine.drug, Molecular interactions, Molecular dynamics, Active site, biology.protein, biology, Enzyme, chemistry.chemical_classification, chemistry, Ritonavir
25 references, page 1 of 2

Anand, K., Palm, G.J., Mesters, J.R., Siddell, S.G., Ziebuhr, J., Hilgenfeld, R.. Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an a-extra helical domain. EMBO J.. 2002; 21: 3213-3224 [OpenAIRE] [PubMed]

Anand, K., Ziebuhr, J., Wadhwani, P., Mesters, J.R., Hilgenfeld, R.. Coronavirus main protease (3CLpro) structure: basis for design of anti-SARS drugs. Science. 2003; 300: 1763-1767 [OpenAIRE] [PubMed]

Carlson, H.A.. Protein flexibility and drug design: how to hit a moving target. Curr. Opin. Chem. Biol.. 2002; 6: 447-452 [PubMed]

Carlson, H.A., McCammon, J.A.. Accommodating protein flexibility in computational drug design. Mol. Pharmacol.. 2000; 57: 213-218 [PubMed]

Case, D.A., Pearlman, J.W., Caldwell, T.E., Cheatham, J., Wang, W.S., Ross, C.L., Simmerling, T.A., Darden, K.M., Merz, R.V., Stanton, A.L., Cheng, J.J., Vincent, M., Crowley, V., Tsui, H., Gohlke, R.J., Radmer, Y., Duan, J., Pitera, I., Massova, G.L., Seibel, U.C., Singh, P.K., Kollman, P.A.. 2002

Cornell, W.D., Cieplak, P., Bayly, C.I., Gould, I.R., Merz, K.M., Ferguson, D.M., Spellmeyer, D.C., Fox, T., Caldwell, J.W., Kollman, P.A.. A second generation force-field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc.. 1995; 117: 5179-5197

Donnelly, C.A., Ghani, A.C., Leung, G.M., Hedley, A.J., Fraser, C., Riley, S., Abu-Raddad, L.J., Ho, L.-M., Thach, T.-Q., Chau, P., Chan, K.-P., Lam, T.-H., Tse, L.-Y., Tsang, T., Liu, S.-H., Kong, J.H.B., Lau, E.M.C., Ferguson, N.M., Anderson, R.M.. Epidermiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003; 361: 1761-1766 [OpenAIRE] [PubMed]

Hornak, V., Okur, A., Rizzo, R.C., Simmerling, C.. HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations. Proc. Natl. Acad. Sci. USA. 2006; 103: 915-920 [OpenAIRE] [PubMed]

Hornak, V., Okur, A., Rizzo, R.C., Simmerling, C.. HIV-1 protease flaps spontaneously close to the correct structure in simulations following manual placement of an inhibitor into the open state. J. Am. Chem. Soc.. 2006; 128: 2812-2813 [OpenAIRE] [PubMed]

Hsu, M.-F., Kuo, C.-J., Chang, K.-T., Chang, H.-C., Chou, C.-C., Ko, T.-P., Shr, H.-L., Chang, G.-G., Wang, A.H.J., Liang, P.-H.. Mechanism of the maturation process of SARS-CoV 3CL protease. J. Biol. Chem.. 2005; 280: 31257-31266 [OpenAIRE] [PubMed]

Huang, C., Wei, P., Fan, K., Liu, Y., Lai, L.. 3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism. Biochemistry. 2004; 43: 4568-4574 [PubMed]

Jenwitheesuk, E., Samudrala, R.. Identifying inhibitors of the SARS coronavirus proteinase. Bioorg. Med. Chem. Lett.. 2003; 13: 3989-3992 [OpenAIRE] [PubMed]

Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W., Klein, M.L.. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys.. 1983; 79: 926-935

Kuiken, T., Fouchier, R.A.M., Schutten, M., Rimmelzwaan, G.F., van Amerongen, G., van Riel, D., Laman, J.D., de Jong, T., van Doornum, G., Lim, W., Ling, A.E., Chan, P.K.S., Tam, J.S., Zambon, M.C., Gopal, R., Drosten, C., van der Werf, S., Escriou, N., Manuguerra, J.-C., Stöhr, K., Peiris, J.S.M., Osterhaus, A.D.M.E.. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003; 362: 263-270 [OpenAIRE] [PubMed]

Lee, T.W., Cherney, M.M., Huitema, C., Liu, J., James, K.E., Powers, J.C., Eltis, L.D., James, M.N.G.. Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like aza-peptide epoxide. J. Mol. Biol.. 2005; 353: 1137-1151 [OpenAIRE] [PubMed]

25 references, page 1 of 2
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