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Remdesivir -- Gilead Sciences Inc.

Target: RNA-dependent RNA polymerase

Relenza Molecule Ball and Spacefill/CPK

The Remdesivir Molecule

 

Remdesivir Chemical Structure

Remdesivir Molecular Formula: C27H35N6O8P

Remdesivir, or GS-5734, is an adenosine triphosphate analog first described in the literature in 2016 as a potential treatment for Ebola. In 2017, its activity against the coronavirus family of viruses was also demonstrated. Remdesivir is also being researched as a potential treatment to SARS-CoV2, the coronavirus responsible for COVID-19.

"..Early treatment with the experimental antiviral drug remdesivir significantly reduced clinical disease and damage to the lungs of rhesus macaques infected with SARS-CoV-2, the coronavirus that causes COVID-19, according to National Institutes of Health scientists..." Antiviral remdesivir prevents disease progression in monkeys with COVID-19.

Mechanism of Action

Coronaviruses replicate by copying their genetic material using an enzyme known as the RNA-dependent RNA polymerase.

Scientists at the University of Alberta have shown that the drug remdesivir is highly effective in stopping the replication mechanism of the coronavirus that causes COVID-19

Calvin J Gordon, Egor P Tchesnokov, Emma Woolner, Jason K Perry, Joy Y. Feng, Danielle P Porter, Matthias Gotte. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. Journal of Biological Chemistry, April 13, 2020;

Götte likens the RNA-dependent RNA polymerase to the engine of the virus, responsible for synthesizing the virus' genome.

Götte’s lab found that the enzymes can incorporate remdesivir (see below image) , which resembles an RNA building block, into new RNA strands. Shortly after adding remdesivir, the enzyme stops being able to add more RNA subunits. This halts genome replication.

See also: Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir--

The nsp12-nsp7-nsp8 complex bound to the template-primer RNA and triphosphate form of Remdesivir(RTP)

Remdesivir (shown in CPK) above bound to nsp12-nsp7-nsp8

7BV2: The nsp12-nsp7-nsp8 complex bound to the template-primer RNA and triphosphate form of Remdesivir(RTP) Citation: No citation for this structure. -- 3D view from RCSB Protein Data Bank

See: Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase (Available online 28 April 2020)

Clinical Trials using Remdesivir

Gilead study in patients with moderate disease
Gilead study in patients with severe disease
NIAID study
INSERM study
China study in patient with mild/moderate disease
China study in patients with severe disease

Covid Anti-Viral Drugs

Currently there are only three anti-viral drugs that directly target Sars-Cov-2





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