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Human Cytomegalovirus UL97 Kinase Is Involved in the Mechanism of Action of Methylenecyclopropane Analogs with 6-Ether and -Thioether Substitutions
TLDR
HCMV UL97 kinase is involved in the antiviral action of these MCPNs, but the in vitro selection of UL97-defective viruses suggests that their activity against more typical ganciclovir-resistant growth-competent UL97 mutants may be relatively preserved.
Cytomegalovirus Mutants Resistant to Ganciclovir and Cidofovir Differ in Susceptibilities to Synguanol and Its 6-Ether and 6-Thioether Derivatives
TLDR
The methylenecyclopropane nucleoside (MCPN) analogs synguanol and its 6-alkoxy and 6-alksylthio derivatives retained good in vitro activities against several common ganciclovir-resistant UL97 kinase variants of human cytomegalovirus.
Hopping of a processivity factor on DNA revealed by single-molecule assays of diffusion
TLDR
The results indicate that UL42 “hops” rather than “slides,” i.e., it microscopically dissociates from and reassociates with DNA as it diffuses rather than remaining so intimately associated with DNA that cation condensation on the phosphate backbone does not affect its motion.
Synthesis and Antiviral Activities of Methylenecyclopropane Analogs with 6-Alkoxy and 6-Alkylthio Substitutions That Exhibit Broad-Spectrum Antiviral Activity against Human Herpesviruses
TLDR
A large set of monohydroxymethyl compounds with ether and thioether substituents at the 6 position of the purine was synthesized and evaluated for antiviral activity against a range of human herpesviruses, suggesting that they might be useful as broad-spectrum antiherpesvirus agents and may be effective in the treatment of resistant virus infections.
The Positively Charged Surface of Herpes Simplex Virus UL42 Mediates DNA Binding*
TLDR
It is suggested that the basic back face of UL42 contacts DNA and that positive charge on this surface is important for this interaction, and the effects of ionic strength on DNA binding by UL42 are estimated.
Molecular Mechanism Underlying the Action of Influenza A Virus Fusion Inhibitor MBX2546.
TLDR
Both binding and stabilization of HA are required for the inhibition of viral infection and the binding of HA by MBX2546 represses the low-pH-induced conformational change in the HA, which is a prerequisite for membrane fusion.
Human Herpesvirus 6 U69 Kinase Phosphorylates the Methylenecyclopropane Nucleosides Cyclopropavir, MBX 2168, and MBX 1616 to Their Monophosphates
TLDR
Dihydroxymethyl and monohydroxym methyl methylenecyclopropane nucleosides are effective inhibitors of both variants of human herpesvirus 6 (HHV-6) and their mechanism of action was investigated.
Activation of 6-Alkoxy-Substituted Methylenecyclopropane Nucleoside Analogs Requires Enzymatic Modification by Adenosine Deaminase-Like Protein 1
TLDR
It is concluded that ADAL-1 is the enzyme responsible for removing the moiety from the guanine ring of MBX-2168-MP prior to conversion to a TP, the active compound that inhibits the viral DNA polymerase.
A Small Covalent Allosteric Inhibitor of Human Cytomegalovirus DNA Polymerase Subunit Interactions.
TLDR
A novel covalent inhibitor of polymerase subunit interactions may serve as a starting point for new, needed drugs to treat human cytomegalovirus infections.
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