Nirmatrelvir Resistance—de Novo E166V/L50V Mutations in an Immunocompromised Patient Treated With Prolonged Nirmatrelvir/Ritonavir Monotherapy Leading to Clinical and Virological Treatment Failure

Nirmatrelvir Resistance—de Novo E166V/L50V Mutations in an Immunocompromised Patient Treated With Prolonged Nirmatrelvir/Ritonavir Monotherapy Leading to Clinical and Virological Treatment Failure—a Case Report

Published:2023-08-19 Issue: Volume: Page:
ISSN:1058-4838
Container-title:Clinical Infectious Diseases
language:en
Short-container-title:

Author:

Zuckerman Neta S¹,Bucris Efrat¹,Keidar-Friedman Danielle²³,Amsalem Muriel²,Brosh-Nissimov Tal⁴⁵^ORCID

Affiliation:

1. Central Virology Laboratory, Ministry of Health , Tel Hashomer , Israel

2. Microbiology Laboratory, Samson Assuta Ashdod University Hospital , Ashdod , Israel

3. Emerging Infectious Diseases Laboratory, Samson Assuta Ashdod University Hospital , Ashdod , Israel

4. Infectious Diseases Unit, Samson Assuta Ashdod University Hospital , Ashdod , Israel

5. Faculty of Health Sciences, Ben Gurion University in the Negev , Beer Sheba , Israel

Abstract

Abstract Resistance of SARS-CoV-2 to antivirals was shown to develop in immunocompromised individuals receiving remdesivir. We describe an immunocompromised patient who was treated with repeated and prolonged courses of nirmatrelvir and developed de-novo E166V/L50F mutations in the Mpro region. These mutations were associated with clinical and virological treatment failure.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Link

https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciad494/51501853/ciad494.pdf

Reference11 articles.

1. SARS-CoV-2 variants in patients with immunosuppression;Corey;N Engl J Med,2021

2. Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: a GISAID exploratory analysis;Focosi;Antiviral Res,2022

3. Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance;Ip;eBioMedicine,2023

4. Remdesivir resistance in transplant recipients with persistent coronavirus disease 2019 (COVID-19);Hogan;Clin Infect Dis,2022

5. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report;Gandhi;Nat Commun,2022

Cited by 32 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Nirmatrelvir and molnupiravir maintain potent in vitro and in vivo antiviral activity against circulating SARS-CoV-2 omicron subvariants;Antiviral Research;2024-10

2. Pomotrelvir and Nirmatrelvir Binding and Reactivity with SARS‐CoV‐2 Main Protease: Implications for Resistance Mechanisms from Computations;Angewandte Chemie International Edition;2024-09-02

3. Structural review of SARS-CoV-2 antiviral targets;Structure;2024-09

4. Jun12682, a potent SARS-CoV-2 papain-like protease inhibitor with exceptional antiviral efficacy in mice;Acta Pharmaceutica Sinica B;2024-09

5. Drug susceptibility and the potential for drug-resistant SARS-CoV-2 emergence in immunocompromised animals;iScience;2024-09