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TRENDING OPEN SCIENCE
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Host-directed therapies against early-lineage SARS-CoV-2 retain
efficacy against B.1.1.7 variant
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By
Ann-Kathrin Reuschl
Lucy Thorne
Lorena Zuliani Alvarez
Mehdi Bouhaddou
Kirsten Obernier
Joseph Hiatt
Margaret Soucheray
Jane Turner
Jacqueline Fabius
Gina T. Nguyen
Danielle Swaney
Romel Rosales
Kris M. White
Pablo Aviles
Ilsa T Kirby
James E Melnyk
Ying Shi
Ziyang Zhang
Kevan Shokat
Adolfo Garcia-Sastre
Clare Jolly
Gregory J Towers
Nevan J Krogan
DOI: 10.1101/2021.01.24.427991
On bioRxiv: https://biorxiv.org/content/10.1101/2021.01.24.427991v1
Coronavirus disease 2019 (COVID-19), caused by severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in
millions of deaths worldwide and massive societal and economic burden.
Recently, a new variant of SARS-CoV-2, known as B.1.1.7, was first
detected in the United Kingdom and is spreading in several other
countries, heightening public health concern and raising questions as
to the resulting effectiveness of vaccines and therapeutic
interventions. We and others previously identified host-directed
therapies with antiviral efficacy against SARS-CoV-2 infection. Less
prone to the development of therapy resistance, host-directed drugs
represent promising therapeutic options to combat emerging viral
variants as host genes possess a lower propensity to mutate compared
to viral genes. Here, in the first study of the full-length B.1.1.7
variant virus, we find two host-directed drugs, plitidepsin (aplidin;
inhibits translation elongation factor eEF1A) and ralimetinib
(inhibits p38 MAP kinase cascade), as well as remdesivir, to possess
similar antiviral activity against both the early-lineage SARS-CoV-2
and the B.1.1.7 variant, evaluated in both human gastrointestinal and
lung epithelial cell lines. We find that plitidepsin is over an order
of magnitude more potent than remdesivir against both viruses. These
results highlight the importance of continued development of host-
directed therapeutics to combat current and future coronavirus variant
outbreaks.
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