Sustained viral response in a hepatitis C virus-infected chimpanzee via a combination of direct-acting antiviral agents.
Efforts to develop novel, interferon-sparing therapies for treatment of chronic hepatitis C (HCV) infection are contingent on the ability of combination therapies consisting of direct antiviral inhibitors to achieve a sustained virologic response. This work demonstrates a proof of concept that coadministration of the nucleoside analogue MK-0608 with the protease inhibitor MK-7009, both of which produced robust viral load declines as monotherapy, to an HCV-infected chimpanzee can achieve a cure of infection.
Antiviral Research Department, Merck Research Laboratories, West Point, PA 19486, USA. david_olsen@merck.com
David B
DB
Olsen
Mary-Ellen
ME
Davies
Larry
L
Handt
Kenneth
K
Koeplinger
Nanyan Rena
NR
Zhang
Steven W
SW
Ludmerer
Donald
D
Graham
Nigel
N
Liverton
Malcolm
M
MacCoss
Daria
D
Hazuda
Steven S
SS
Carroll
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D054833:Isoindoles; D047029:Lactams, Macrocyclic; D007930:Leucine / Q000031:analogs & derivatives; D002679:Pan troglodytes / Q000821:virology*; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides; D016896:Treatment Outcome; D014372:Tubercidin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D003521:Cyclopropanes; D007211:Indoles; D054833:Isoindoles; D047029:Lactams, Macrocyclic; D007930:Leucine; D011392:Proline; D011480:Protease Inhibitors; D013449:Sulfonamides; D014372:Tubercidin; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C540393:vaniprevir; C518645:7-deaza-2'-C-methyladenosine