Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives
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 co...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.606097/full |
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| author | Cheng-Wei Yang Yue-Zhi Lee Hsing-Yu Hsu Jia-Tsrong Jan Yi-Ling Lin Sui-Yuan Chang Tzu-Ting Peng Ruey-Bing Yang Jian-Jong Liang Chun-Che Liao Tai-Ling Chao Yu-Hau Pang Han-Chieh Kao Wen-Zheng Huang Jiunn-Horng Lin Chun-Ping Chang Guang-Hao Niu Szu-Huei Wu Huey-Kang Sytwu Chiung-Tong Chen Shiow-Ju Lee |
| author_facet | Cheng-Wei Yang Yue-Zhi Lee Hsing-Yu Hsu Jia-Tsrong Jan Yi-Ling Lin Sui-Yuan Chang Tzu-Ting Peng Ruey-Bing Yang Jian-Jong Liang Chun-Che Liao Tai-Ling Chao Yu-Hau Pang Han-Chieh Kao Wen-Zheng Huang Jiunn-Horng Lin Chun-Ping Chang Guang-Hao Niu Szu-Huei Wu Huey-Kang Sytwu Chiung-Tong Chen Shiow-Ju Lee |
| author_sort | Cheng-Wei Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T03:03:52Z |
| format | Article |
| id | doaj.art-8f3073d60ef14ac5858cb1186503592c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T03:03:52Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-8f3073d60ef14ac5858cb1186503592c2022-12-21T23:19:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-12-011110.3389/fphar.2020.606097606097Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based DerivativesCheng-Wei Yang0Yue-Zhi Lee1Hsing-Yu Hsu2Jia-Tsrong Jan3Yi-Ling Lin4Sui-Yuan Chang5Tzu-Ting Peng6Ruey-Bing Yang7Jian-Jong Liang8Chun-Che Liao9Tai-Ling Chao10Yu-Hau Pang11Han-Chieh Kao12Wen-Zheng Huang13Jiunn-Horng Lin14Chun-Ping Chang15Guang-Hao Niu16Szu-Huei Wu17Huey-Kang Sytwu18Chiung-Tong Chen19Shiow-Ju Lee20Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanGenomic Research Center, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, TaiwanAnimal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanInstitute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, TaiwanInstitute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, TaiwanInstitute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, TaiwanAnimal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu, TaiwanAnimal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, TaiwanTylophorine-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.https://www.frontiersin.org/articles/10.3389/fphar.2020.606097/fullHCoV-OC43HCoV-229EFIPVtylophorineSARS-CoV-2ouabain |
| spellingShingle | Cheng-Wei Yang Yue-Zhi Lee Hsing-Yu Hsu Jia-Tsrong Jan Yi-Ling Lin Sui-Yuan Chang Tzu-Ting Peng Ruey-Bing Yang Jian-Jong Liang Chun-Che Liao Tai-Ling Chao Yu-Hau Pang Han-Chieh Kao Wen-Zheng Huang Jiunn-Horng Lin Chun-Ping Chang Guang-Hao Niu Szu-Huei Wu Huey-Kang Sytwu Chiung-Tong Chen Shiow-Ju Lee Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives Frontiers in Pharmacology HCoV-OC43 HCoV-229E FIPV tylophorine SARS-CoV-2 ouabain |
| title | Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives |
| title_full | Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives |
| title_fullStr | Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives |
| title_full_unstemmed | Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives |
| title_short | Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives |
| title_sort | inhibition of sars cov 2 by highly potent broad spectrum anti coronaviral tylophorine based derivatives |
| topic | HCoV-OC43 HCoV-229E FIPV tylophorine SARS-CoV-2 ouabain |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.606097/full |
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