4.7 Article

Synthesis and biological evaluation of novel rhodanine-based structures with antiviral activity towards HHV-6 virus

Journal

BIOORGANIC CHEMISTRY
Volume 119, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2021.105518

Keywords

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Funding

  1. HHV-6 foundation grant
  2. FISM -Fondazione Italiana Sclerosi Multipla [2019/R-Single/004]
  3. '5 per mille' public funding

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Compounds synthesized by researchers showed significant antiviral activity in human cells, with 9e demonstrating a lasting inhibitory effect on viral replication for over 7 days, indicating support for the use of these amphipathic fusion inhibitors in treating HHV-6 infections.
An increased awareness of diseases associated with Human herpesvirus 6 (HHV-6) infection or reactivation has resulted in a growing interest in the evaluation of the best treatment options available for the clinical management of HHV-6 disease. However, no compound has yet been approved exclusively for HHV-6 infection treatment. For this reason, the identification of anti-HHV6 compounds provides a valuable opportunity for developing efficient antiviral therapies. A possible target for antiviral drugs is the virus-cell fusion step. In this study, we synthetized potential fusion intermediates inhibitors based on the rhodanine structure. The obtained derivatives were tested for cytotoxicity and for antiviral activity in human cells infected with HHV6. Level of infection was monitored by viral DNA quantification at different time points up to 7 days post infection. Among the synthetized derivatives, 9e showed a significative inhibitory effect on viral replication that lasted over 7 days, probably attributable to the particular combination of hydrophilic and hydrophobic substituents to the rhodanine moiety. Our results support the use of these amphipathic fusion inhibitors for the treatment of HHV-6 infections.

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