User talk:Daniel Hausaman
From Proteopedia
| Line 20: | Line 20: | ||
== Structural highlights == | == Structural highlights == | ||
| - | <Structure load=' | + | <Structure load='7BV2' size='400' frame='true' align='right' caption='The nsp12-nsp7-nsp8 complex bound to the template-primer RNA and triphosphate form of Remdesivir(RTP)' scene='Insert optional scene name here' /> |
| - | == References | + | ==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 | ||
| + | |||
| + | == References == | ||
Revision as of 00:10, 15 January 2021
Contents |
Remdesivir
Introduction
SARS-CoV-2 also known as severe acute respiratory syndrome coronavirus 2 or COVID-19 is a respiratory disease that is capable of progressing to viral pneumonia and can also lead to death. 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.
Function
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. Furthermore 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.
Mechanism
Disease
Relevance
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
