The Author ensures that the research has been conducted responsibly and ethically with adherence to all relevant regulations. read more..
Department of Pharmacy, GRD Institutes, India
*Corresponding author:Mohammad Asif, Department of Pharmacy, GRD Institutes, India
Submission: October 10, 2017; Published: July 05, 2018
ISSN : 2576-9170Volume2 Issue2
Activities of pyridazinones as inhibitors of the hepatitis C viral polymerase. These pyridazinones bind to the hepatitis C virus non-structural protein 5B (NS5B). Hepatitis C virus (HCV) RNA-dependent RNA polymerase, referred to as non-structural protein 5B (NS5B), is responsible for replication of the viral genome and is essential in the life cycle of the virus. Recently, active-site and allosteric NS5B inhibitors have appeared. Some 3(2H)-pyridazinones exhibited potent activity as inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their Drug Metabolism and Pharmacokinetics (DMPK) profiles. It has long been considered an attractive target for the development of direct acting antiviral (DAA) agents. This investigation led to the discovery of potent inhibitors with improved DMPK properties which displayed potent inhibitory activities, good stability toward human liver microsomes, and high ratios of liver to plasma concentrations. In vitro DMPK data for many of the compounds are disclosed and a crystal structure of a representative inhibitor complexed with the NS5B protein.
Keywords: Antiviral agents; NS5B polymerase; HIV-1 reverse transcriptase; Pyridazinones; Hepatitis C virus; RNA-dependent; RNA polymerase; NS5B inhibitors; DMPK profiling
Abbreviations: NS5B: Non-Structural Protein 5B; HCV: Hepatitis C Virus; DMPK: Drug Metabolism and Pharmacokinetics; DAA: Direct Acting Antiviral; RDRP: RNA-Dependent RNA Polymerase; Peg-IFN: Pegylated Interferon; RBV: Ribavirin; HLM: Human Liver Microsomes; MLM: Monkey Liver Microsomes
Ph.D in Agriculture from Faculty of Agriculture, Tohoku University
Research Professor, PhD, Holistic Research Institute
Professor, Chief Doctor, Director of Department of Pediatric Surgery, Associate Director of Department of Surgery, Doctoral Supervisor Tongji hospital, Tongji medical college, Huazhong University of Science and Technology
Senior Research Engineer and Professor, Center for Refining and Petrochemicals, Research Institute, King Fahd University of Petroleum and Minerals (KFUPM), Dhahran, Saudi Arabia
Fellow of International Agency for Standards and Ratings (IASR), Edith Cowan University, Sarich Neuroscience Research Institute
Chancellor Emeritus / Professor Emeritus of Chemistry and Physics, University of Missouri–St. Louis
Ph.D in Science from the Federal University of Alagoas, UFAL, Brazil
Assistant Professor in College of Architecture, Art and Design
Interim Dean, College of Education and Health Sciences, Director of Biomechanics Laboratory, Sport Science Innovation Program, Bridgewater State University
Professor of numerous training courses in Family Medicine
Assistant Professor, Department of Electronics and Computer Science
Wenzhou Medical University, China
Fooyin University, Taiwan
Saglik Bilimleri University, Turkey
Vincent Pol University, Poland
National Defence University of Malaysia, Malaysia
Dogus University, Turkey
Hope College, USA
Russian Academy of Sciences, Russia
Southern Cross University, Australia
Umm Al-Qura University, Saudi Arabia
City University of New York, USA
Khalifa University of Science & Technology, United Arab Emirates
Hebei Normal University, China
Alexandria University, Egypt
Indian Institute of Technology Kharagpur, India
Council for Agriculture Research and Analysis of Agri Economy (CREA), Italy
King Fahd University of Petroleum and Minerals, Saudi Arabia
King Abdulaziz University, Saudi Arabia
University of Oregon, USA
University of Edinburgh, Scotland
University of Tennessee, USA
Central University of Venezuela, Venezuela
Islamic Azad University Central Tehran Branch, Iran
Tourin University, Italy
Teaching & Public Speaking, Spain
Paeditric Hospital "Giovanni XXIII", Italy
University of Nicosia, Cyprus
Universidad Miguel Hernández de Elche, Spain
Oral Roberts University, USA
Beijing Normal University, China
Howard University, USA
Edith Cowan University, Australia
Dubai Health Authority, UAE
University of Minnesota, USA
Indian Institute of Technology Kharagpur, India
Serhal Hospital, Lebanon
University of Malta, Malta
National Center for Global Health and Medicine, Japan
Molloy College, USA
Federal University of Piauí, Brazil
Krankenhaus Nordwest Hospital, Germany
Laval University, Canada
Cinvestav-Unidad Saltillo, Mexico
UPMC Hamot Neuroscience Institute, USA
Ramon Llull University, Spain
White Bear Associates, LLC, USA
Lehigh University, USA
California Southern University, USA
Institute of Solid State Physics of RAS, Russia
University of Buenos Aires, Argentina
Mansoura University, Egypt
King Saud University, Saudi Arabia
University of Coimbra, Portugal