IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32045-1.html
   My bibliography  Save this article

SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model

Author

Listed:
  • Carolin M. Lieber

    (Georgia State University)

  • Robert M. Cox

    (Georgia State University)

  • Julien Sourimant

    (Georgia State University)

  • Josef D. Wolf

    (Georgia State University)

  • Kate Juergens

    (University of Washington)

  • Quynh Phung

    (University of Washington)

  • Manohar T. Saindane

    (Emory University)

  • Meghan K. Smith

    (Emory University)

  • Zachary M. Sticher

    (Emory University)

  • Alexander A. Kalykhalov

    (Emory University)

  • Michael G. Natchus

    (Emory University)

  • George R. Painter

    (Emory University)

  • Kaori Sakamoto

    (University of Georgia)

  • Alexander L. Greninger

    (University of Washington)

  • Richard K. Plemper

    (Georgia State University)

Abstract

SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency against omicron is unknown. This study evaluates molnupiravir against VOC in human airway epithelium organoids, ferrets, and a lethal Roborovski dwarf hamster model of severe COVID-19-like lung injury. VOC were equally inhibited by molnupiravir in cells and organoids. Treatment reduced shedding in ferrets and prevented transmission. Pathogenicity in dwarf hamsters was VOC-dependent and highest for delta, gamma, and omicron. All molnupiravir-treated dwarf hamsters survived, showing reduction in lung virus load from one (delta) to four (gamma) orders of magnitude. Treatment effect size varied in individual dwarf hamsters infected with omicron and was significant in males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir in human trials and alerts that benefit must be reassessed in vivo as VOC evolve.

Suggested Citation

  • Carolin M. Lieber & Robert M. Cox & Julien Sourimant & Josef D. Wolf & Kate Juergens & Quynh Phung & Manohar T. Saindane & Meghan K. Smith & Zachary M. Sticher & Alexander A. Kalykhalov & Michael G. N, 2022. "SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32045-1
    DOI: 10.1038/s41467-022-32045-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32045-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32045-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Mathilde Richard & Adinda Kok & Dennis Meulder & Theo M. Bestebroer & Mart M. Lamers & Nisreen M. A. Okba & Martje Fentener van Vlissingen & Barry Rockx & Bart L. Haagmans & Marion P. G. Koopmans & Ro, 2020. "SARS-CoV-2 is transmitted via contact and via the air between ferrets," Nature Communications, Nature, vol. 11(1), pages 1-6, December.
    2. Robert M. Cox & Josef D. Wolf & Carolin M. Lieber & Julien Sourimant & Michelle J. Lin & Darius Babusis & Venice DuPont & Julie Chan & Kim T. Barrett & Diane Lye & Rao Kalla & Kwon Chun & Richard L. M, 2021. "Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    3. Petra Mlcochova & Steven A. Kemp & Mahesh Shanker Dhar & Guido Papa & Bo Meng & Isabella A. T. M. Ferreira & Rawlings Datir & Dami A. Collier & Anna Albecka & Sujeet Singh & Rajesh Pandey & Jonathan B, 2021. "SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion," Nature, Nature, vol. 599(7883), pages 114-119, November.
    4. Kyle Rosenke & Frederick Hansen & Benjamin Schwarz & Friederike Feldmann & Elaine Haddock & Rebecca Rosenke & Kent Barbian & Kimberly Meade-White & Atsushi Okumura & Shanna Leventhal & David W. Hawman, 2021. "Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    5. Angela Wahl & Lisa E. Gralinski & Claire E. Johnson & Wenbo Yao & Martina Kovarova & Kenneth H. Dinnon & Hongwei Liu & Victoria J. Madden & Halina M. Krzystek & Chandrav De & Kristen K. White & Kendra, 2021. "SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801," Nature, Nature, vol. 591(7850), pages 451-457, March.
    6. Delphine Planas & David Veyer & Artem Baidaliuk & Isabelle Staropoli & Florence Guivel-Benhassine & Maaran Michael Rajah & Cyril Planchais & Françoise Porrot & Nicolas Robillard & Julien Puech & Matth, 2021. "Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization," Nature, Nature, vol. 596(7871), pages 276-280, August.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Juan Liu & Fengfeng Mao & Jianhe Chen & Shuaiyao Lu & Yonghe Qi & Yinyan Sun & Linqiang Fang & Man Lung Yeung & Chunmei Liu & Guimei Yu & Guangyu Li & Ximing Liu & Yuansheng Yao & Panpan Huang & Dongx, 2023. "An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Robert M. Cox & Carolin M. Lieber & Josef D. Wolf & Amirhossein Karimi & Nicole A. P. Lieberman & Zachary M. Sticher & Pavitra Roychoudhury & Meghan K. Andrews & Rebecca E. Krueger & Michael G. Natchu, 2023. "Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Haofeng Wang & Qi Yang & Xiaoce Liu & Zili Xu & Maolin Shao & Dongxu Li & Yinkai Duan & Jielin Tang & Xianqiang Yu & Yumin Zhang & Aihua Hao & Yajie Wang & Jie Chen & Chenghao Zhu & Luke Guddat & Hong, 2023. "Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Laurent Renia & Yun Shan Goh & Angeline Rouers & Nina Bert & Wan Ni Chia & Jean-Marc Chavatte & Siew‐Wai Fong & Zi Wei Chang & Nicole Ziyi Zhuo & Matthew Zirui Tay & Yi-Hao Chan & Chee Wah Tan & Nicho, 2022. "Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Delphine Planas & Isabelle Staropoli & Vincent Michel & Frederic Lemoine & Flora Donati & Matthieu Prot & Francoise Porrot & Florence Guivel-Benhassine & Banujaa Jeyarajah & Angela Brisebarre & Océane, 2024. "Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Bruno A. Rodriguez-Rodriguez & Grace O. Ciabattoni & Ralf Duerr & Ana M. Valero-Jimenez & Stephen T. Yeung & Keaton M. Crosse & Austin R. Schinlever & Lucie Bernard-Raichon & Joaquin Rodriguez Galvan , 2023. "A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Hassen Kared & Asia-Sophia Wolf & Amin Alirezaylavasani & Anthony Ravussin & Guri Solum & Trung The Tran & Fridtjof Lund-Johansen & John Torgils Vaage & Lise Sofie Nissen-Meyer & Unni C. Nygaard & Ola, 2022. "Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Suman Das & Janmejay Singh & Heena Shaman & Balwant Singh & Anbalagan Anantharaj & Patil Sharanabasava & Rajesh Pandey & Rakesh Lodha & Anil Kumar Pandey & Guruprasad R. Medigeshi, 2022. "Pre-existing antibody levels negatively correlate with antibody titers after a single dose of BBV152 vaccination," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    7. Biao Zhou & Runhong Zhou & Bingjie Tang & Jasper Fuk-Woo Chan & Mengxiao Luo & Qiaoli Peng & Shuofeng Yuan & Hang Liu & Bobo Wing-Yee Mok & Bohao Chen & Pui Wang & Vincent Kwok-Man Poon & Hin Chu & Ch, 2022. "A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Nozomi Kuse & Yu Zhang & Takayuki Chikata & Hung The Nguyen & Shinichi Oka & Hiroyuki Gatanaga & Masafumi Takiguchi, 2022. "Long-term memory CD8+ T cells specific for SARS-CoV-2 in individuals who received the BNT162b2 mRNA vaccine," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    9. Valeria Calvaresi & Antoni G. Wrobel & Joanna Toporowska & Dietmar Hammerschmid & Katie J. Doores & Richard T. Bradshaw & Ricardo B. Parsons & Donald J. Benton & Chloë Roustan & Eamonn Reading & Micha, 2023. "Structural dynamics in the evolution of SARS-CoV-2 spike glycoprotein," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Byung Uk Lee, 2021. "Why Does the SARS-CoV-2 Delta VOC Spread So Rapidly? Universal Conditions for the Rapid Spread of Respiratory Viruses, Minimum Viral Loads for Viral Aerosol Generation, Effects of Vaccination on Viral," IJERPH, MDPI, vol. 18(18), pages 1-6, September.
    11. Haogao Gu & Ahmed Abdul Quadeer & Pavithra Krishnan & Daisy Y. M. Ng & Lydia D. J. Chang & Gigi Y. Z. Liu & Samuel M. S. Cheng & Tommy T. Y. Lam & Malik Peiris & Matthew R. McKay & Leo L. M. Poon, 2023. "Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Haisheng Yu & Banghui Liu & Yudi Zhang & Xijie Gao & Qian Wang & Haitao Xiang & Xiaofang Peng & Caixia Xie & Yaping Wang & Peiyu Hu & Jingrong Shi & Quan Shi & Pingqian Zheng & Chengqian Feng & Guofan, 2023. "Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Wenkai Han & Ningning Chen & Xinzhou Xu & Adil Sahil & Juexiao Zhou & Zhongxiao Li & Huawen Zhong & Elva Gao & Ruochi Zhang & Yu Wang & Shiwei Sun & Peter Pak-Hang Cheung & Xin Gao, 2023. "Predicting the antigenic evolution of SARS-COV-2 with deep learning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Nikhil Kumar Tulsian & Raghuvamsi Venkata Palur & Xinlei Qian & Yue Gu & Bhuvaneshwari D/O Shunmuganathan & Firdaus Samsudin & Yee Hwa Wong & Jianqing Lin & Kiren Purushotorman & Mary McQueen Kozma & , 2023. "Defining neutralization and allostery by antibodies against COVID-19 variants," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    15. Yin-Feng Kang & Cong Sun & Jing Sun & Chu Xie & Zhen Zhuang & Hui-Qin Xu & Zheng Liu & Yi-Hao Liu & Sui Peng & Run-Yu Yuan & Jin-Cun Zhao & Mu-Sheng Zeng, 2022. "Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Meriem Bekliz & Kenneth Adea & Pauline Vetter & Christiane S. Eberhardt & Krisztina Hosszu-Fellous & Diem-Lan Vu & Olha Puhach & Manel Essaidi-Laziosi & Sophie Waldvogel-Abramowski & Caroline Stephan , 2022. "Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    17. Daiki Yamaguchi & Odgerel Chimed-Ochir & Yui Yumiya & Eisaku Kishita & Tomoyuki Akita & Junko Tanaka & Tatsuhiko Kubo, 2024. "Potential Risk Factors to COVID-19 Severity: Comparison of SARS-CoV-2 Delta- and Omicron-Dominant Periods," IJERPH, MDPI, vol. 21(3), pages 1-11, March.
    18. Wang, Jian & Jiang, Wenjing & Wu, Xinpei & Yang, Mengdie & Shao, Wei, 2023. "Role of vaccine in fighting the variants of COVID-19," Chaos, Solitons & Fractals, Elsevier, vol. 168(C).
    19. Rajeshwer S. Sankhala & Kerri G. Lal & Jaime L. Jensen & Vincent Dussupt & Letzibeth Mendez-Rivera & Hongjun Bai & Lindsay Wieczorek & Sandra V. Mayer & Michelle Zemil & Danielle A. Wagner & Samantha , 2024. "Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. de León, Ugo Avila-Ponce & Avila-Vales, Eric & Huang, Kuan-lin, 2022. "Modeling COVID-19 dynamic using a two-strain model with vaccination," Chaos, Solitons & Fractals, Elsevier, vol. 157(C).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32045-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.