Miravirsen

Miravirsen (INN; codenamed SPC3649) is an experimental drug for the treatment of hepatitis C, being developed by Santaris Pharma. As of 2017 it was in Phase II clinical trials.[1]

Miravirsen

Clinical data
Other names	SPC3649
Routes of administration	Intravenous or subcutaneous injection
ATC code	none
Legal status
Legal status	Investigational
Identifiers
IUPAC name RNA, (P-thio)((2'-O,4'-C-methylene)m5C-dC-(2'-O,4'-C-methylene)A-dT-dT-(2'-O,4'-C-methylene)G-(2'-O,4'-C-methylene)m5U-dC-dA-(2'-O,4'-C-methylene)m5C-dA-(2'-O,4'-C-methylene)m5C-dT-(2'-O,4'-C-methylene)m5C-(2'-O,4'-C-methylene)m5C)
CAS Number	1072874-90-8
PubChem CID	56843415
UNII	Q083AJW7VS
Chemical and physical data
Formula	C151H185N49O83P14S14
Molar mass	4896.87 g·mol−1
SMILES CC1=CN([C@H]2CC(OP(O)(=S)OC[C@H]3O[C@H](CC3OP(O)(=S)OC[C@@]34COC([C@@H](O3)N3C=NC5=C3N=C(N)NC5=O)C4OP(O)(=S)OC[C@@]34COC([C@@H](O3)N3C=C(C)C(=O)NC3=O)C4OP(O)(=S)OC[C@H]3O[C@H](CC3OP(O)(=S)OC[C@H]3O[C@H](CC3OP(O)(=S)OC[C@@]34COC([C@@H](O3)N3C=CC(N)=NC3=O)C4OP(O)(=S)OC[C@H]3O[C@H](CC3OP(O)(=S)OC[C@@]34COC([C@@H](O3)N3C=CC(N)=NC3=O)C4OP(O)(=S)OC[C@H]3O[C@H](CC3OP(O)(=S)OC[C@@]34COC([C@@H](O3)N3C=CC(N)=NC3=O)C4OP(O)(=S)OC[C@]34COC(C3O)[C@@H](O4)N3C=CC(N)=NC3=O)N3C=C(C)C(=O)NC3=O)N3C=NC4=C3N=CN=C4N)N3C=NC4=C3N=CN=C4N)N3C=CC(N)=NC3=O)N3C=C(C)C(=O)NC3=O)[C@@H](COP(O)(=S)OC3C4OC[C@]3(COP(O)(=S)OC3C[C@@H](O[C@@H]3COP(O)(=S)OC3C5OC[C@]3(CO)O[C@H]5N3C=CC(N)=NC3=O)N3C=CC(N)=NC3=O)O[C@H]4N3C=NC4=C3N=CN=C4N)O2)C(=O)NC1=O

Miravirsen had been given by subcutaneous injection in early clinical trials as of 2017.[1] It is antisense to a human microRNA called miR-122. miR-122 ferries an argonaute protein to 5'-UTR region of viral RNA, where it binds, protecting the RNA from being destroyed by normally present nucleases; by binding to miR-122, miravirsen removes that protection and the virus RNA can be destroyed.[1] There is some evidence that the 5'-UTR region mutates under repeated exposure to miravirsen.[1]

Miravirsen is a modified oligonucleotide consisting of a chain of 15 nucleotides, the base sequence of which is designed to selectively bind to miR-122.[1][2] Seven of the 15 sugar units are deoxyriboses, and the other eight are riboses with an additional bridge between the 2' oxygen and the 4' carbon atoms; this makes the molecule a locked nucleic acid. Furthermore, the phosphate units have been replaced by thiophosphates.[2]

The complete base sequence is

mC*-dC-A*-dT-dT-G*-mU*-dC-dA-mC*-dA-mC*-dT-mC*-mC* [d = 2'-deoxy, * = 2'-O,4'-C-methylene, i.e. bridged or "locked" sugar]

with 3'→5' thiophosphate linkages.[2]

• 
  Chemical structure of a single nucleoside (sugar plus base) of a locked nucleic acid