Related Experiment Video
Updated: Jul 13, 2026
11:14
Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay
Published on: November 10, 2013
Metal chelators as antiviral agents
Thorsten Kirschberg1, Jay Parrish
1Gilead Sciences Inc, 333 Lakeside Drive, Foster City, CA 94404, USA. tkirschberg@gilead.com
Current Opinion in Drug Discovery & Development
|July 31, 2007
Summary
Viral replication enzymes utilize magnesium. Inhibiting these enzymes by coordinating magnesium in their active sites is a promising antiviral strategy. This review covers drug development programs targeting these enzymes.
Area of Science:
- Biochemistry
- Virology
- Medicinal Chemistry
Background:
- Viral replication relies on enzymes that process nucleotide substrates.
- These enzymes often use divalent magnesium cations for catalysis.
- High intracellular magnesium levels and magnesium's affinity for oxyanions are critical factors.
Purpose of the Study:
- To review antiviral drug development programs targeting viral enzymes.
- Focus on programs initiated from alpha,gamma-diketo acid leads.
- To summarize structure-activity relationships for magnesium binding inhibitors.
Main Methods:
- Review of pharmaceutical research and clinical trial data.
- Analysis of structure-activity relationships (SAR) for enzyme inhibitors.
- Focus on compounds designed for high-affinity magnesium binding.
Main Results:
- Active-site metal coordination is a validated approach for viral inhibition.
- Several drug development programs have progressed to late-stage clinical trials.
- Key structure-activity relationships for magnesium binding have been identified.
Conclusions:
- Targeting viral enzymes through magnesium coordination represents a successful antiviral strategy.
- Alpha,gamma-diketo acid derivatives have yielded promising drug candidates.
- Understanding magnesium binding is crucial for developing effective antiviral therapies.
More Related Videos
Related Concept Videos
01:21Antiprotozoal Agents
Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...
01:22Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
02:51Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
00:56Extraction: Advanced Methods
Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is formed in...
01:17Antidotes
Antidotes are medicinal substances used to counteract the harmful effects of toxins or drugs in the body. They function in various ways, each uniquely designed to combat specific toxic compounds.
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...
Specific antidotes operate by inhibiting the enzymes that control biochemical pathways, reducing the production of harmful metabolites.
An example of an antidote is atropine, which counteracts the detrimental effects of cholinesterase inhibitors. It achieves this by deactivating muscarinic receptors,...
01:19Complexation Equilibria: The Chelate Effect
In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...