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Review

Recent advances in S-adenosyl-L-homocysteine hydrolase inhibitors and their potential clinical applications

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Pages 1197-1206 | Published online: 25 Feb 2005

Bibliography

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  • •Comprehensive review on SAH hydrolase as a target for antiviral drug design: from rationale to drug synthesis.
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  • ••One of the earliest articles to described the effectiveness ofSAH hydrolase inhibitors as immunosuppressants in animal models.
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  • •For the first time, the x-ray structure of SAH hydrolase was determined in the absence of an inhibitor. The enzyme exists with its binding site in the 'open' form.
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  • •For the first time, the x-ray structure of SAH hydrolase was determined in the presence of a Type I inhibitor of the enzyme. The inactivated enzyme exists in a 'closed' form at the substrate binding site.
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  • ••Data show that SAH hydrolase inhibitors were effectiveagainst Ebola virus infection. SAH hydrolase inhibitors are the only known agents having antiviral activity against Ebola viral infections.
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  • •Identified the first Type II inhibitor of SAH hydrolase that employs the 'hydrolytic activity' of the enzyme.
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  • ••For the first time it was shown that SAH hydrolase inhibitorsselectively inhibited T-cell activation but had no effect on B-cells. Inhibition of T-cell activation by the enzyme inhibitor is related to inhibition of IL-2 production and IL-2R expression.
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  • ••The specific design of a double-blind, randomised,placebo-controlled, multicentre clinical trial (VISP) including patient number, patient eligibility doses of vitamins, end points, and time lines is described.

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