Experimental validation of computationally prioritized bisphosphonates reveals no direct in vitro antiviral activity against SARS-CoV-2
- 1Edith Cowan University
Abstract
It is essential to experimentally evaluate antiviral efficacy predicted by molecular docking and related in silico approaches, which this study achieves for three bisphosphonates (alendronate, minodronate, zoledronate) and treprostinil, identified as potential antiviral therapies in our previous work. These investigational compounds had no detectable cytotoxicity at concentrations up to 25M in Vero E6 cells but also failed to show any antiviral effect against the PQ.8.1 isolate of SARS-CoV-2, when compared to control drugs (ensitrelvir, nirmatrelvir, and remdesivir). It appears that for bisphosphonates, any protective effect is likely due to other virus- or host-mediated mechanisms of action. This study demonstrates the importance of iterating between theoretical hypotheses and experiments to elucidate underlying mechanisms at play.
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BibTeX
@misc{rehman2026experimental,
title = {{Experimental validation of computationally prioritized bisphosphonates reveals no direct in vitro antiviral activity against SARS-CoV-2}},
author = {M. M.-U.- Rehman and S. Olliff and A. McAuley and A. Awasthi and K. V. G. Chandrasekhar and M. Sankranarayanan and S. S. Vasan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.07.749793},
url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749793v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Experimental validation of computationally prioritized bisphosphonates reveals no direct in vitro antiviral activity against SARS-CoV-2
AU - M. M.-U.- Rehman
AU - S. Olliff
AU - A. McAuley
AU - A. Awasthi
AU - K. V. G. Chandrasekhar
AU - M. Sankranarayanan
AU - S. S. Vasan
PY - 2026
DA - 2026/09/07
PB - bioRxiv
DO - 10.64898/2026.09.07.749793
UR - https://www.biorxiv.org/content/10.64898/2026.09.07.749793v1
AB - It is essential to experimentally evaluate antiviral efficacy predicted by molecular docking and related in silico approaches, which this study achieves for three bisphosphonates (alendronate, minodronate, zoledronate) and treprostinil, identified as potential antiviral therapies in our previous work. These investigational compounds had no detectable cytotoxicity at concentrations up to 25M in Vero E6 cells but also failed to show any antiviral effect against the PQ.8.1 isolate of SARS-CoV-2, when compared to control drugs (ensitrelvir, nirmatrelvir, and remdesivir). It appears that for bisphosphonates, any protective effect is likely due to other virus- or host-mediated mechanisms of action. This study demonstrates the importance of iterating between theoretical hypotheses and experiments to elucidate underlying mechanisms at play.
ER -