Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives
| Autor: | Chiung-Tong Chen, Jiunn Horng Lin, Guang Hao Niu, Shiow Ju Lee, Sui-Yuan Chang, Wen Zheng Huang, Jia Tsrong Jan, Tzu Ting Peng, Hsing Yu Hsu, Yi-Ling Lin, Szu Huei Wu, Yu Hau Pang, Han Chieh Kao, Chun-Ping Chang, Jian Jong Liang, Ruey-Bing Yang, Chun Che Liao, Yue Zhi Lee, Tai Ling Chao, Huey-Kang Sytwu, Cheng Wei Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
HCoV-OC43 Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses Transmissible gastroenteritis coronavirus coronavirus medicine.disease_cause 03 medical and health sciences 0302 clinical medicine medicine Pharmacology (medical) Human coronavirus OC43 Original Research Coronavirus EC50 Cytopathic effect Pharmacology Virus quantification FIPV biology Chemistry SARS-CoV-2 tylophorine lcsh:RM1-950 ouabain COVID-19 virus diseases HCoV-229E biology.organism_classification Molecular biology 030104 developmental biology lcsh:Therapeutics. Pharmacology 030220 oncology & carcinogenesis |
| Zdroj: | Frontiers in Pharmacology, Vol 11 (2020) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| Popis: | Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC50 values of up to 8 and 16 nM, respectively Strikingly, the tylophorine-based compounds tested inhibited viral yields of HCoV-OC43 to a much greater extent (7–8 log magnitudes of p f u /ml) than the cardiotonic steroids (about 2–3 log magnitudes of p f u /ml), as determined by end point assays Based on these results, three tylophorine-based compounds were further examined for their anti-viral activities on two other human coronaviruses, HCoV-229E and SARS-CoV-2 These three tylophorine-based compounds inhibited HCoV-229E with EC50 values of up to 6 5 nM, inhibited viral yields of HCoV-229E by 6–7 log magnitudes of p f u /ml, and were also found to inhibit SARS-CoV-2 with EC50 values of up to 2 5–14 nM In conclusion, tylophorine-based compounds are potent, broad-spectrum inhibitors of coronaviruses including SARS-CoV-2, and could be used for the treatment of COVID-19 © Copyright © 2020 Yang, Lee, Hsu, Jan, Lin, Chang, Peng, Yang, Liang, Liao, Chao, Pang, Kao, Huang, Lin, Chang, Niu, Wu, Sytwu, Chen and Lee |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|