O
Osvaldo A. Flores
Researcher at Merck & Co.
Publications - 28
Citations - 1628
Osvaldo A. Flores is an academic researcher from Merck & Co.. The author has contributed to research in topics: Replicon & Hepatitis C virus. The author has an hindex of 16, co-authored 28 publications receiving 1579 citations. Previous affiliations of Osvaldo A. Flores include Isis Pharmaceuticals & United States Military Academy.
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Journal ArticleDOI
Characterization of Resistance to Non-obligate Chain-terminating Ribonucleoside Analogs That Inhibit Hepatitis C Virus Replication in Vitro
Giovanni Migliaccio,Joanne E. Tomassini,Steven S. Carroll,Licia Tomei,Sergio Altamura,Balkrishen Bhat,Linda Bartholomew,Michele Bosserman,Alessandra Ceccacci,Lawrence F. Colwell,Riccardo Cortese,Raffaele De Francesco,Anne B. Eldrup,Krista Getty,Xiaoli S. Hou,Robert L. Lafemina,Steven W. Ludmerer,Malcolm MacCoss,Daniel R. McMasters,Mark Stahlhut,David B. Olsen,Daria J. Hazuda,Osvaldo A. Flores +22 more
TL;DR: 2′-C-methyl-substituted ribonucleosides are efficient chain-terminating inhibitors of HCV genome replication and the combination of these agents with interferon-α results in synergistic inhibition of HCv genome replication in cell culture.
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A 7-Deaza-Adenosine Analog Is a Potent and Selective Inhibitor of Hepatitis C Virus Replication with Excellent Pharmacokinetic Properties
David B. Olsen,Anne B. Eldrup,Linda Bartholomew,Balkrishen Bhat,Michele Bosserman,Alessandra Ceccacci,Lawrence F. Colwell,John F. Fay,Osvaldo A. Flores,Krista Getty,Jay A. Grobler,Robert L. Lafemina,Eric J. Markel,Giovanni Migliaccio,Marija Prhavc,Mark Stahlhut,Joanne E. Tomassini,Malcolm MacCoss,Daria J. Hazuda,Steven S. Carroll +19 more
TL;DR: 7-deaza-2′-C-methyl-adenosine is an attractive candidate for further investigation as a potential treatment for HCV infection and displays promising in vivo pharmacokinetics in three animal species, as well as an acute oral lethal dose in excess of 2,000 mg/kg of body weight in mice.
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Structure−Activity Relationship of Heterobase-Modified 2‘-C-Methyl Ribonucleosides as Inhibitors of Hepatitis C Virus RNA Replication
Anne B. Eldrup,Marija Prhavc,Jennifer L. Brooks,Balkrishen Bhat,Thazha P. Prakash,Quanlai Song,Sanjib Bera,Neelima Bhat,Prasad Dande,P. Dan Cook,C. Frank Bennett,Steven S. Carroll,Richard G Ball,Michele Bosserman,Christine Burlein,Lawrence F. Colwell,John F. Fay,Osvaldo A. Flores,Krista Getty,Robert L. Lafemina,Joseph Leone,Malcolm MacCoss,Daniel R. McMasters,Joanne E Tomassini,Derek Von Langen,Bohdan S. Wolanski,David B. Olsen +26 more
TL;DR: The potency of the 2'-C-methyl-4-amino-pyrrolo[2,3-d]pyrimidine ribonucleosides and their improved pharmacokinetic properties relative to that of 2'- C-methyladenosine suggests that this class of compounds may have clinical utility.
Journal ArticleDOI
Replication Fitness and NS5B Drug Sensitivity of Diverse Hepatitis C Virus Isolates Characterized by Using a Transient Replication Assay
Steven W. Ludmerer,Donald J. Graham,Evelyn Boots,Edward M. Murray,Amy L. Simcoe,Eric J. Markel,Jay A. Grobler,Osvaldo A. Flores,David B. Olsen,Daria J. Hazuda,Robert L. Lafemina +10 more
TL;DR: A transient replicon-based assay is described that can support the clinical development of compounds which target NS5B and demonstrates its utility by examining several patient-derived NS5 B isolates for replication fitness and differential sensitivity toNS5B inhibitors.
Journal ArticleDOI
Generation and Selection of Novel Fully Human Monoclonal Antibodies That Neutralize Dickkopf-1 (DKK1) Inhibitory Function in Vitro and Increase Bone Mass in Vivo
Helmut Glantschnig,Richard Hampton,Ping Lu,Jing Zhang Zhao,Salvatore Vitelli,Lingyi Huang,Peter Haytko,T. Cusick,Cheryl Ireland,Stephen Jarantow,Robin Ernst,Nan Wei,Pascale V. Nantermet,K. R. Scott,John E. Fisher,Fabio Talamo,Laura Orsatti,Alfred A. Reszka,Punam Sandhu,Donald B. Kimmel,Osvaldo A. Flores,William R. Strohl,Zhiqiang An,Fubao Wang +23 more
TL;DR: A rate-limiting function of physiologic DKK1 levels in the regulation of bone mass in intact female mice is demonstrated, amendable to specific pharmacologic neutralization by newly identified DKK 1-IgGs.