ArticleEmerging microbes & infections2021
The preclinical inhibitor GS441524 in combination with GC376 efficaciously inhibited the proliferation of SARS-CoV-2 in the mouse respiratory tract.
Article in Emerging microbes & infections, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Development of GFP-expressing infectious clones for PRRSV using TAR cloning for antiviral drug screening.Npj viruses · 2025Article
- Inhibitory efficacy and structural insights of Bofutrelvir against SARS-CoV-2 MCommunications biology · 2025Article
- SARS-CoV-2 MSLAS discovery : advancing life sciences R & D · 2024Article
- SARS-CoV-2 Main Protease Inhibitors That Leverage Unique Interactions with the Solvent Exposed S3 Site of the Enzyme.ACS medicinal chemistry letters · 2024Article
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- Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.European journal of medicinal chemistry · 2023Review
- SARS-CoV-2 Main Protease Drug Design, Assay Development, and Drug Resistance Studies.Accounts of chemical research · 2023Article
- Roles of host proteases in the entry of SARS-CoV-2.Animal diseases · 2023Review
- Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Adaptive Mutation in the Main Protease Cleavage Site of Feline Coronavirus Renders the Virus More Resistant to Main Protease Inhibitors.Journal of virology · 2022Article
- Beyond the vaccines: a glance at the small molecule and peptide-based anti-COVID19 arsenal.Journal of biomedical science · 2022Review
- Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics.Plants (Basel, Switzerland) · 2022Article
- Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021.International journal of environmental research and public health · 2022Review
- Animal models for studying coronavirus infections and developing antiviral agents and vaccines.Antiviral research · 2022Review
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- Nucleoside analog GS-441524: pharmacokinetics in different species, safety, and potential effectiveness against Covid-19.Pharmacology research & perspectives · 2022Review
- Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays.Acta pharmaceutica Sinica. B · 2022Article
- Recent advances in developing small-molecule inhibitors against SARS-CoV-2.Acta pharmaceutica Sinica. B · 2022Review
- Treatments for COVID-19: Lessons from 2020 and new therapeutic options.Current opinion in pharmacology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unprecedented coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious threat to global public health. Development of effective therapies against SARS-CoV-2 is urgently needed. Here, we evaluated the antiviral activity of a remdesivir parent nucleotide analog, GS441524, which targets the coronavirus RNA-dependent RNA polymerase enzyme, and a feline coronavirus prodrug, GC376, which targets its main protease, using a mouse-adapted SARS-CoV-2 infected mouse model. Our results showed that GS441524 effectively blocked the proliferation of SARS-CoV-2 in the mouse upper and lower respiratory tracts via combined intranasal (i.n.) and intramuscular (i.m.) treatment. However, the ability of high-dose GC376 (i.m. or i.n. and i.m.) was weaker than GS441524. Notably, low-dose combined application of GS441524 with GC376 could effectively protect mice against SARS-CoV-2 infection via i.n. or i.n. and i.m. treatment. Moreover, we found that the pharmacokinetic properties of GS441524 is better than GC376, and combined application of GC376 and GS441524 had a synergistic effect. Our findings support the further evaluation of the combined application of GC376 and GS441524 in future clinical studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.