@article{4f2b62ac45474997b697695650edb351,
title = "Toward Consensus on Correct Interpretation of Protein Binding in Plasma and Other Biological Matrices for COVID-19 Therapeutic Development",
abstract = "The urgent global public health need presented by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has brought scientists from diverse backgrounds together in an unprecedented international effort to rapidly identify interventions. There is a pressing need to apply clinical pharmacology principles and this has already been recognized by several other groups. However, one area that warrants additional specific consideration relates to plasma and tissue protein binding that broadly influences pharmacokinetics and pharmacodynamics. The principles of free drug theory have been forged and applied across drug development but are not currently being routinely applied for SARS-CoV-2 antiviral drugs. Consideration of protein binding is of critical importance to candidate selection but requires correct interpretation, in a drug-specific manner, to avoid either underinterpretation or overinterpretation of its consequences. This paper represents a consensus from international researchers seeking to apply historical knowledge, which has underpinned highly successful antiviral drug development for other viruses, such as HIV and hepatitis C virus for decades.",
author = "Marta Boffito and Back, {David J.} and Charles Flexner and Peter Sj{\"o} and Blaschke, {Terrence F.} and Horby, {Peter W.} and Dario Cattaneo and Acosta, {Edward P.} and Peter Anderson and Andrew Owen",
note = "Funding Information: M.B. declares travel grants, speaker engagements, advisory roles, and research grants from Janssen, Roche, ViiV, Bristol‐Myers Squibb, Merck Sharp & Dohme, Gilead, Mylan, Cipla, and Teva. D.J.B. has received honoraria or advisory board payments from Abbvie, Gilead, ViiV, Merck, Janssen, and educational grants from Abbvie, Gilead, ViiV, Merck, Janssen, and Novartis. C.F. reports serving as a paid consultant for Gilead Sciences, Merck, and ViiV Healthcare. P.S. is an employee of Drugs for Neglected Disease initiative. D.C. has received consultant fees from ViiV Healthcare and speaker{\textquoteright}s fees from MSD, Pfizer, Angelini, ViiV, and Janseen Cilag. P.A. has received personal fees and research funding paid to his institution from Gilead Sciences. A.O. is a Director of Tandem Nano Ltd. and has received research funding from ViiV, Merck, and Janssen, and consultancy from Gilead, ViiV, and Merck not related to the current paper. All other authors declared no competing interests for this work. Funding Information: The authors received no funding for the current work. P.S. acknowledges the Federal Ministry of Education and Research (BMBF) through KfW, Germany and thanks the donors contributing to DNDi?s overall mission: UK aid, UK; M?decins Sans Fronti?res International and the Swiss Agency for Development and Cooperation (SDC), Switzerland. P.H. acknowledges funding support from UKRI/NIHR (MC_PC_19056); Wellcome/DFiD (215091/Z/18/Z). P.A. acknowledges funding support from NIH (AI122298). A.O. acknowledges research funding from EPSRC (EP/R024804/1; EP/S012265/1), NIH (R01AI134091; R24AI118397), European Commission (761104) and Unitaid (project LONGEVITY). Funding Information: The authors received no funding for the current work. P.S. acknowledges the Federal Ministry of Education and Research (BMBF) through KfW, Germany and thanks the donors contributing to DNDi{\textquoteright}s overall mission: UK aid, UK; M{\'e}decins Sans Fronti{\`e}res International and the Swiss Agency for Development and Cooperation (SDC), Switzerland. P.H. acknowledges funding support from UKRI/NIHR (MC_PC_19056); Wellcome/DFiD (215091/Z/18/Z). P.A. acknowledges funding support from NIH (AI122298). A.O. acknowledges research funding from EPSRC (EP/R024804/1; EP/S012265/1), NIH (R01AI134091; R24AI118397), European Commission (761104) and Unitaid (project LONGEVITY). Publisher Copyright: {\textcopyright} 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.",
year = "2021",
month = jul,
doi = "10.1002/cpt.2099",
language = "English (US)",
volume = "110",
pages = "64--68",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "1",
}