Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Novel Synergistic Anti-Enteroviral Drug Combinations

Aleksandr Ianevski
* ,
Eva Zusinaite
,
Tanel Tenson
ORCID logo ,
Valentyn Oksenych
,
Wei Wang
,
Jan Egil Afset
,
Magnar Bjørås
ORCID logo ,
Denis E Kainov
* ORCID logo
Version 1 : Received: 31 July 2022 / Approved: 2 August 2022 / Online: 2 August 2022 (05:01:21 CEST)

A peer-reviewed article of this Preprint also exists.

Ianevski, A.; Zusinaite, E.; Tenson, T.; Oksenych, V.; Wang, W.; Afset, J.E.; Bjørås, M.; Kainov, D.E. Novel Synergistic Anti-Enteroviral Drug Combinations. Viruses 2022, 14, 1866. Ianevski, A.; Zusinaite, E.; Tenson, T.; Oksenych, V.; Wang, W.; Afset, J.E.; Bjørås, M.; Kainov, D.E. Novel Synergistic Anti-Enteroviral Drug Combinations. Viruses 2022, 14, 1866.

Abstract

Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved vaccines or treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir-vemurafenib, vemurafenib-pleconaril and rupintrivir-pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their combinations may have fewer side effects in vivo and therefore should be further studied in pre- and clinical trials.

Keywords

Echovirus; enterovirus; broad-spectrum antiviral agent; antiviral drug combination; antiviral strategy

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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