Development of Ultrapure and Potent Tannic Acids as a Pan-coronal Antiviral Therapeutic.

Autor: Shih PC; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Mao YW; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Hu JW; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Hsieh HY; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Shih TM; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Lu LP; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Chang WH; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Huang CH; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Lin CH; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Lin CH; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Tan P; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Yang YC; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Chien MH; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Su CC; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Yeh CH; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Chuang PY; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Hsieh TL; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Wang CC; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan., Hsieh PS; Institute of Physiology, National Defense Medical Center, Taipei City 11490, Taiwan.; Department of Medical Research, Tri-Service General Hospital, Taipei City 114, Taiwan., Chou TY; Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei City 112, Taiwan.; Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei City 112304, Taiwan., Tsai GE; Department of Research and Development, SyneuRx International (Taiwan) Corp., New Taipei City 22175, Taiwan.; UCLA School of Medicine, Los Angeles, California 90095, United States.
Jazyk: angličtina
Zdroj: ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2022 May 13; Vol. 5 (6), pp. 400-412. Date of Electronic Publication: 2022 May 13 (Print Publication: 2022).
DOI: 10.1021/acsptsci.1c00264
Abstrakt: The rampageous transmission of SARS-CoV-2 has been devastatingly impacting human life and public health since late 2019. The waves of pandemic events caused by distinct coronaviruses at present and over the past decades have prompted the need to develop broad-spectrum antiviral drugs against them. In this study, our Pentarlandir ultrapure and potent tannic acids (UPPTA) showed activities against two coronaviral strains, SARS-CoV-2 and HCoV-OC43, the earliest-known coronaviruses. The mode of inhibition of Pentarlandir UPPTA is likely to act on 3-chymotrypsin-like protease (3CLpro) to prevent viral replication, as supported by results of biochemical analysis, a 3CLpro assay, and a "gain-of-function" 3CLpro overexpressed cell-based method. Even in the 3CLpro overexpressed environment, Pentarlandir UPPTA remained its antiviral characteristic. Utilizing cell-based virucidal and cytotoxicity assays, the 50% effective concentrations (EC 50 ) and 50% cytotoxicity concentration (CC 50 ) of Pentarlandir UPPTA were determined to be ∼0.5 and 52.5 μM against SARS-CoV-2, while they were 1.3 and 205.9 μM against HCoV-OC43, respectively. In the pharmacokinetic studies, Pentarlandir UPPTA was distributable at a high level to the lung tissue with no accumulation in the body, although the distribution was affected by the food effect. With further investigation in toxicology, Pentarlandir UPPTA demonstrated an overall safe toxicology profile. Taking these findings together, Pentarlandir UPPTA is considered to be a safe and efficacious pancoronal antiviral drug candidate that has been advanced to clinical development.
Competing Interests: The authors declare the following competing financial interest(s): All authors, except for Po-Shiuan Hsieh and Teh-Ying Chou, are employees of SyneuRx International (Taiwan) Corp.
(© 2022 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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