NS5B: Difference between revisions

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==RNA Dependent RNA Polymerase from Hepatitis C Virus==

In 2019, there were approximately 290,000 deaths due to a Hepatitis C infection. The majority of these deaths were largely due to the long-term adverse effects such as, cirrhosis and liver cancer. Currently in the world, about 58 million people are chronically infected with the Hepatitis C virus and there are about 1.5 million new infections annually. In the United States, data estimates that 2.4 million people are infected with Hepatitis C. Due to the low percentage of diagnoses and the frequency of acute infection, it is believed that the number of Hepatitis C infections can range anywhere from 2.5 million to 4.7 million infected individuals. Nearly all of RNA viruses depend on specific activities performed by RNA dependent RNA polymerases (RdRp). These activities importantly include the copying of the RNA sequence and facilitating the process of transcription. Therefore, if a vaccine was created to target the RNA dependent RNA polymerase and inhibit the function of this protein, then the viral genome could not be replicated. If replication halts, the infection cannot spread to other cells. Due to the viral dependence on RdRps, it is essential to understand the structure for further antiviral drug research.

'''NS5B''' is the '''RNA dependent RNA polymerase''' of Hepatitis C virus. NS5B, like other RNA dependent RNA polymerases, is error prone. This viral RNA replicase is of approximately a million times lower fidelity than a replicative prokayrotic or eukaryotic DNA polymerase. This is due in part to the fact that NS5B contains no exonuclease or proofreading domain. IN NS5B two divalent cations coordinated by carboxyl groups (as seen in DNA polymerases) catalyze the polymerization of monomers of RNA triphosphates to extend a primer strand, that may have initiated ''de novo''. In the case of NS5B the residues that coordinate divalent cations (Mg2+ or Mn2+ ''in vitro'') are the three <scene name='NS5B/Native_ns5b/7'>active site aspartates (220, 318 and 319)</scene> seen here (PDB entry [[2hai]]).

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 <StructureSection load='2HAI_catalytic3.pdb' size='350' side='right' scene='NS5B/Cv/3' caption='Hepatitis virus NS5B RNA polymerase complex with inhibitor (PDB code [[2hai]])'>
 ==RNA Dependent RNA Polymerase from Hepatitis C Virus==
+In 2019, there were approximately 290,000 deaths due to a Hepatitis C infection. The majority of these deaths were largely due to the long-term adverse effects such as, cirrhosis and liver cancer. Currently in the world, about 58 million people are chronically infected with the Hepatitis C virus and there are about 1.5 million new infections annually. In the United States, data estimates that 2.4 million people are infected with Hepatitis C. Due to the low percentage of diagnoses and the frequency of acute infection, it is believed that the number of Hepatitis C infections can range anywhere from 2.5 million to 4.7 million infected individuals. Nearly all of RNA viruses depend on specific activities performed by RNA dependent RNA polymerases (RdRp). These activities importantly include the copying of the RNA sequence and facilitating the process of transcription. Therefore, if a vaccine was created to target the RNA dependent RNA polymerase and inhibit the function of this protein, then the viral genome could not be replicated. If replication halts, the infection cannot spread to other cells. Due to the viral dependence on RdRps, it is essential to understand the structure for further antiviral drug research.
 '''NS5B''' is the '''RNA dependent RNA polymerase''' of Hepatitis C virus. NS5B, like other RNA dependent RNA polymerases, is error prone. This viral RNA replicase is of approximately a million times lower fidelity than a replicative prokayrotic or eukaryotic DNA polymerase. This is due in part to the fact that NS5B contains no exonuclease or proofreading domain. IN NS5B two divalent cations coordinated by carboxyl groups (as seen in DNA polymerases) catalyze the polymerization of monomers of RNA triphosphates to extend a primer strand, that may have initiated ''de novo''. In the case of NS5B the residues that coordinate divalent cations (Mg2+ or Mn2+ ''in vitro'') are the three <scene name='NS5B/Native_ns5b/7'>active site aspartates (220, 318 and 319)</scene> seen here (PDB entry [[2hai]]).