Synthesis and activity of an octapeptide inhibitor designed for SARS coronavirus main proteinase

Gan, Yi Ru; Huang, He; Huang, Yong; Rao, Chun Ming; Zhao, Yang; Liu, Jin Sheng; Wu, Lei; Wei, Dong

doi:10.1016/j.peptides.2005.09.006

Cited by 60 publications

(53 citation statements)

References 21 publications

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“…A octapeptide AVLQSGFR designed by us was synthesized and its antiviral potential against SARS coronavirus (BJ-01) was assessed, which demonstrates that AVLQSGFR is the most active in inhibiting replication of the SARS coronavirus compared with other compounds reported so far [8]. Its EC50 is 2.7×10 -2 mg/l, and its corresponding selectivity index is over 3704.…”

Section: Other Anti-virus Ihibitor Investigationsmentioning

confidence: 91%

Discovery of Anti-Hiv Drugs Using Computer Aided Drug Designing Tools

Wang

LinLi²,

Wei³

2007

2007 1st International Conference on Bioinformatics and Biomedical Engineering

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As the information era dawns, computer aided drug design has become an indispensable component in current drug industries. Many good works have done using computer aided drug design tools. As more and more efforts have been put into the discovery of anti-HIV drugs, our investigation interesting has been focused on the anti-HIV drug design. In our study of anti-HIV inhibitor design, we have obtained a number of significant achievements by incorporating miscellaneous modules of different drug design software's with HIV protease (HIV Pr) as the main target. Furthermore, we also applied computer aided drug design tools to other anti-virus investigations, such as SARS and H5N1 influenza virus. Some significant results have been gained, which are useful for the anti-virus inhibitor design in future.

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Section: Other Anti-virus Ihibitor Investigationsmentioning

confidence: 91%

Discovery of Anti-Hiv Drugs Using Computer Aided Drug Designing Tools

Wang

LinLi²,

Wei³

2007

2007 1st International Conference on Bioinformatics and Biomedical Engineering

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“…The cleavage mechanism and the interaction between the octapeptide and SARS-CoV M pro were subsequently predicted by Du et al [66]. Gan et al reported that this octapeptide exhibits good activity (IC 50 = 0.031 µM) with no toxicity on Vero cells [67]. Modification of AVLQSGFR on its cleavable sites such as replacing the carboxyl group CO of glutamine on subsite R1 by CH 2 or CF 2 or replacing the NH of serine on subsite R1' by CH 2 in the peptide bond (Gln) CO=NH (Ser), was proposed by Du et al to increase the resistance to enzyme hydrolysis while still tightly bound to the active site [68].…”

Section: Pro Protease Inhibitorsmentioning

confidence: 94%

Antiviral Drug Discovery Against SARS-CoV

Wu¹,

Lin²,

Hsu³

et al. 2006

CMC

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Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.

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“…Meanwhile, AVLQSGFR, the first octapeptide introduced in this area by Chou et al [4], was experimentally demonstrated to be cleavable by the SARS enzyme with a high bioactivity by Gan et al [45]. It has been observed that the hydrophilic and hydrophobic complimentary interaction is important in the ligand-receptor interaction [30].…”

Section: Peptide Inhibitorsmentioning

confidence: 99%

“…These findings were acquired thru a series of studies by combining the approaches of structural bioinformatics, pharmacophore modeling, virtual screening, molecular docking, peptide-cleavage site prediction, and the "distorted-key" theory [18]. Some of the findings have already been experimentally proved (see, e.g., [45]). …”

Section: Detection Of Sars-coronavirusmentioning

confidence: 99%

Progress in Computational Approach to Drug Development Against SARS

Chou¹,

Wei²,

Du³

et al. 2006

CMC

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Since the outbreak of SARS (severe acute respiratory syndrome) in November 2002 in Southern China's Guangdong Province, considerable progress has been made in the development of drugs for SARS therapy. The present mini review is focused on the area of computer-aided drug discovery, i.e., the advances achieved mainly from the approaches of structural bioinformatics, pharmacophore modeling, molecular docking, peptide-cleavage site prediction, and other computational means. It is highlighted that the compounds C(28)H(34)O(4)N(7)Cl, C(21)H(36(O)5)N(6) and C(21)H(36)O(5)N(6) (Wei et al., Amino Acids, 2006, 31: 73-80), as well as KZ7088 (Chou et al. Biochem. Biophys. Res. Commun., 2003, 308: 148-151), a derivative of AG7088, might be the promising candidates for further investigation, and that the octapeptides ATLQAIAS and ATLQAENV, as well as AVLQSGFR, might be converted to effective inhibitors against the SARS enzyme. Meanwhile, how to modify these octapeptides based on the "distorted key" theory to make them become potent inhibitors is explicitly elucidated. Finally, a brief introduction is given for how to use computer-generated graphs to rapidly diagnose SARS coronavirus.

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Synthesis and activity of an octapeptide inhibitor designed for SARS coronavirus main proteinase

Cited by 60 publications

References 21 publications

Discovery of Anti-Hiv Drugs Using Computer Aided Drug Designing Tools

Discovery of Anti-Hiv Drugs Using Computer Aided Drug Designing Tools

Antiviral Drug Discovery Against SARS-CoV

Progress in Computational Approach to Drug Development Against SARS

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