Kevin M Coombs, Roger DuMoulin-White, Arkady Mandel
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Infectious agents account for millions of deaths every year. The Herpes Simplex Viruses (HSVs) are large double-stranded DNA viruses that infect more than 90% of the human population and can establish life-long latency in human hosts. Currently, effective FDA approved anti-herpetic drugs include acyclovir and later-generation derivatives (valacyclovir and famciclovir), which inhibit viral DNA synthesis. In previous work, we demonstrated that the small molecule Ruvidar® could inhibit numerous pathogenic human viruses when added to solutions of viruses both with and without light activation. In these experiments, we evaluated the ability of Ruvidar® to restrict HSV-1 replication in Vero cells, both by itself and in combination with acyclovir and metformin in the absence of light activation to mimic deep tissue. Ruvidar® successfully inhibited HSV-1 replication at significantly lower concentrations and more effectively than either acyclovir or metformin alone. We also discovered additive and synergistic anti-HSV-1 effects when combinational therapy was tested. Ruvidar® also restricted HSV-1 replication in human U251 glioblastoma astrocytoma cells, remained highly effective against acyclovir-resistant HSV-1 mutants, and protected infected cells from virus-induced cytopathology.
期刊介绍:
Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.