Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A-Reference-Cited by-同舟云学术

Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A

Published:2021-02-26 Issue:6532 Volume:371 Page:926-931
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

White Kris M.¹²^ORCID,Rosales Romel¹²^ORCID,Yildiz Soner¹²^ORCID,Kehrer Thomas¹²^ORCID,Miorin Lisa¹²^ORCID,Moreno Elena¹²^ORCID,Jangra Sonia¹²,Uccellini Melissa B.¹²^ORCID,Rathnasinghe Raveen¹²^ORCID,Coughlan Lynda³^ORCID,Martinez-Romero Carles¹²^ORCID,Batra Jyoti⁴⁵⁶⁷^ORCID,Rojc Ajda⁴⁵⁶⁷^ORCID,Bouhaddou Mehdi⁴⁵⁶⁷^ORCID,Fabius Jacqueline M.⁴⁶,Obernier Kirsten⁴⁵⁶⁷^ORCID,Dejosez Marion⁸^ORCID,Guillén María José⁹,Losada Alejandro⁹,Avilés Pablo⁹,Schotsaert Michael¹²^ORCID,Zwaka Thomas⁸^ORCID,Vignuzzi Marco¹⁰^ORCID,Shokat Kevan M.⁴⁶⁷¹¹^ORCID,Krogan Nevan J.¹⁴⁵⁶⁷^ORCID,García-Sastre Adolfo¹²¹²¹³^ORCID

Affiliation:

1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

2. Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

3. Department of Microbiology and Immunology and Center for Vaccine Development and Global Health (CVD), University of Maryland School of Medicine, Baltimore, MD, USA.

4. Quantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.

5. J. David Gladstone Institutes, San Francisco, CA 94158, USA.

6. QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA.

7. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.

8. Huffington Foundation Center for Cell-Based Research in Parkinson’s Disease, Department of Cell, Developmental, and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

9. Research and Development Department, PharmaMar, 28770 Colmenar Viejo, Madrid, Spain.

10. Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Institut Pasteur, 75724 Paris Cedex 15, France.

11. Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.

12. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

13. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

Hurting the virus by targeting the host Many host proteins play a role in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some are required for viral replication and translation. There are efforts toward finding drugs that target viral proteins, but a complementary approach is to target these required host proteins. White et al. explored the antiviral activity of the cyclic depsipeptide drug plitidepsin, which targets the hosts cell's translational machinery (see the Perspective by Wong and Damania). The authors show that in cells, the drug is substantially more potent than remdesivir against SARS-CoV-2, with limited cellular toxicity. Prophylactic treatment protected mice against SARS-CoV-2 infection, so further investigation of plitidepsin as a therapeutic is warranted. Science , this issue p. 926 ; see also p. 884

Funder

U.S. Department of Defense

NIH Office of the Director

JPB Foundation

Defense Sciences Office, DARPA

Hoffman-La Roche

Huffington Foundation

Laboratoire d’Excellence ‘‘Integrative Biology of Emerging Infectious Diseases’’ grant

the Roddenberry Foundation

Fast Grant for COVID-19 from the Emergent Ventures program at the Mercatus Center of George Mason University

Laboratory for Genomics Research (LGR) Excellence in Research Award (ERA) from the Innovative Genomics Institute at UC Berkeley

Swiss National Science Foundation