User talk:Daniel Hausaman
From Proteopedia
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| - | ==Remdesivir== | + | ==Use of Remdesivir as a treatment for COVID-19== |
== Introduction == | == Introduction == | ||
| - | SARS-CoV-2 is the virus that is responsible for the disease COVID-19 which is a respiratory disease that can inflict damage to multiple major organs including the heart, brain and lungs. SARS-Cov2 relies upon RNA-dependent RNA polymerase (RdRp) to replicate the viral genetic material. Drugs such as nucleoside analogues can be used to inhibit this enzyme and stop viral replication. | + | Remdesivir is a drug that was initially developed for use against Ebola, and has shown to be effective against coronaviruses such as SARS-CoV, MERS-CoV, SARS-CoV-2. |
| + | SARS-CoV-2 is the virus that is responsible for the disease COVID-19 which is a respiratory disease that can inflict severe damage to multiple major organs including the heart, brain and lungs. SARS-Cov2 relies upon RNA-dependent RNA polymerase (RdRp) to replicate the viral genetic material. Drugs such as nucleoside analogues can be used to inhibit this enzyme and stop viral replication. | ||
Remdesivir initially labeled GS-5734 is an adenosine triphosphate analogue, used as a broad-spectrum antiviral drug meaning it can be used to inhibit a wide range of viruses that rely upon RNA-dependent RNA polymerase for genomic replication. | Remdesivir initially labeled GS-5734 is an adenosine triphosphate analogue, used as a broad-spectrum antiviral drug meaning it can be used to inhibit a wide range of viruses that rely upon RNA-dependent RNA polymerase for genomic replication. | ||
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==Structure== | ==Structure== | ||
| - | On the right-hand side shows the 3D structure of nsp12-nsp7-nsp8 complex bound to the template-primer RNA and the triphosphate form of remdesivir which is highlighted in blue to view remdesivir bound to the protein complex <scene name='86/867374/1/1'>click here</scene> | + | On the right-hand side shows the 3D structure of nsp12-nsp7-nsp8 complex also known as the RdRp bound to the template-primer RNA and the triphosphate form of remdesivir which is highlighted in blue to view remdesivir bound to the protein complex <scene name='86/867374/1/1'>click here</scene> |
== Mechanism == | == Mechanism == | ||
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Once administered remdesivir requires metabolic activation, this takes place after the drug diffuses into a cell. Phosphoamidase (HINT1) and esterases CES1 and CTSA transform remdesivir into GS-441524 mono-phosphate. This is then phosphorylated again to produce the active triphosphate analog. | Once administered remdesivir requires metabolic activation, this takes place after the drug diffuses into a cell. Phosphoamidase (HINT1) and esterases CES1 and CTSA transform remdesivir into GS-441524 mono-phosphate. This is then phosphorylated again to produce the active triphosphate analog. | ||
| - | Remdeisvir is a polymerase inhibitor, there are 2 main categories for polymerase inhibitors these are known as nucleoside analogues and allosteric inhibitors. Nucleoside analogues resemble viral building blocks such as Adenosine triphosphate. One of the main ways this inhibits viral replication is because of competitive inhibition between the nucleoside analogue and the viral RNA. To view the RNA highlighted in red <scene name='86/867374/2/1'>Click here</scene> | + | Remdeisvir is a polymerase inhibitor, there are 2 main categories for polymerase inhibitors these are known as nucleoside analogues and allosteric inhibitors. Nucleoside analogues resemble viral building blocks such as Adenosine triphosphate. One of the main ways this inhibits viral replication is because of competitive inhibition between the nucleoside analogue and the viral RNA. To view the RNA highlighted in red <scene name='86/867374/2/1'>Click here</scene> viral replication can also be reduced by the incorporation of incorrect nucleotides into the viral genome this can result in chain termination. In addition to this replication with incorrect nucleosides can produce multiple mutations for the virus that can affect RNA synthesis resulting in abnormal proteins further reducing the virulence of the virus. |
Revision as of 22:52, 5 July 2021
Contents |
Use of Remdesivir as a treatment for COVID-19
Introduction
Remdesivir is a drug that was initially developed for use against Ebola, and has shown to be effective against coronaviruses such as SARS-CoV, MERS-CoV, SARS-CoV-2. SARS-CoV-2 is the virus that is responsible for the disease COVID-19 which is a respiratory disease that can inflict severe damage to multiple major organs including the heart, brain and lungs. SARS-Cov2 relies upon RNA-dependent RNA polymerase (RdRp) to replicate the viral genetic material. Drugs such as nucleoside analogues can be used to inhibit this enzyme and stop viral replication. Remdesivir initially labeled GS-5734 is an adenosine triphosphate analogue, used as a broad-spectrum antiviral drug meaning it can be used to inhibit a wide range of viruses that rely upon RNA-dependent RNA polymerase for genomic replication.
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Structure
On the right-hand side shows the 3D structure of nsp12-nsp7-nsp8 complex also known as the RdRp bound to the template-primer RNA and the triphosphate form of remdesivir which is highlighted in blue to view remdesivir bound to the protein complex
Mechanism
Once administered remdesivir requires metabolic activation, this takes place after the drug diffuses into a cell. Phosphoamidase (HINT1) and esterases CES1 and CTSA transform remdesivir into GS-441524 mono-phosphate. This is then phosphorylated again to produce the active triphosphate analog.
Remdeisvir is a polymerase inhibitor, there are 2 main categories for polymerase inhibitors these are known as nucleoside analogues and allosteric inhibitors. Nucleoside analogues resemble viral building blocks such as Adenosine triphosphate. One of the main ways this inhibits viral replication is because of competitive inhibition between the nucleoside analogue and the viral RNA. To view the RNA highlighted in red viral replication can also be reduced by the incorporation of incorrect nucleotides into the viral genome this can result in chain termination. In addition to this replication with incorrect nucleosides can produce multiple mutations for the virus that can affect RNA synthesis resulting in abnormal proteins further reducing the virulence of the virus.
Structural highlights
Structure
On the right-hand side shows the 3D structure of nsp12-nsp7-nsp8 complex bound to the template-primer RNA and the triphosphate form of remdesivir which is highlighted in blue to view remdesivir bound to the protein complex
