Broad-Spectrum In Vitro Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524)

Article Chemistry, Medicinal

Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models

Yingjun Li et al.

Summary: The article reports that the parent nucleoside of remdesivir, GS-441524, shows potent inhibition of SARS-CoV-2 replication and has high efficacy in reducing viral titers in infected organs without notable toxicity in animal studies.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Review Microbiology

Remdesivir against COVID-19 and Other Viral Diseases

Jakob J. Malin et al.

Summary: Remdesivir is the first approved treatment for COVID-19, showing therapeutic and prophylactic effects in animal models of various viruses. However, it failed in a clinical trial on ebolavirus disease but showed beneficial effects for patients with COVID-19 in a placebo-controlled trial.

CLINICAL MICROBIOLOGY REVIEWS (2021)

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Article Immunology

The preclinical inhibitor GS441524 in combination with GC376 efficaciously inhibited the proliferation of SARS-CoV-2 in the mouse respiratory tract

Yuejun Shi et al.

Summary: The study found that in a mouse model infected with SARS-CoV-2, GS441524 effectively blocked the replication of the virus through intranasal and intramuscular treatment, whereas the efficacy of GC376 was weaker. A low-dose combination of GS441524 and GC376 could effectively protect mice from infection and showed a synergistic effect when used together.

EMERGING MICROBES & INFECTIONS (2021)

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Article Chemistry, Medicinal

Prodrugs of a 1′-CN-4-Aza-7,9-dideazaadenosine C-Nucleoside Leading to the Discovery of Remdesivir (GS-5734) as a Potent Inhibitor of Respiratory Syncytial Virus with Efficacy in the African Green Monkey Model of RSV

Richard L. Mackman et al.

Summary: A discovery program identified C-nucleoside 4 as a potential lead compound for respiratory syncytial virus (RSV), which led to the discovery of the more potent drug remdesivir. In vitro metabolism studies confirmed the rapid formation of the active metabolite 1-NTP, and in vivo studies in monkeys showed significant reduction in lung viral load following administration of remdesivir. These early data supported the potential of remdesivir as a novel treatment for RSV prior to its development for other diseases.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Microbiology

Rethinking Remdesivir: Synthesis, Antiviral Activity, and Pharmacokinetics of Oral Lipid Prodrugs

Robert T. Schooley et al.

Summary: Remdesivir is currently the only FDA-approved antiviral drug for treating SARS-CoV-2 infection, but its intravenous administration limits its use to hospitalized patients. Effective orally bioavailable antiviral drugs are urgently needed, with several in clinical development. New oral lipid prodrugs of remdesivir have shown promising anti-SARS-CoV-2 activity in various cell types.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

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Article Immunology