Anti-SARS-CoV‑2 Potential of Artemisinins In Vitro
The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a clust...
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| Published in | ACS infectious diseases Vol. 6; no. 9; pp. 2524 - 2531 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
11.09.2020
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC50 values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC50 of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development. |
|---|---|
| AbstractList | The discovery of novel drug candidates with anti-severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is
critical for the control of the global COVID-19 pandemic.
Artemisinin, an old antimalarial drug derived from Chinese
herbs, has saved millions of lives. Artemisinins are a cluster
of artemisinin-related drugs developed for the treatment of
malaria and have been reported to have multiple pharmacological
activities, including anticancer, antiviral, and immune
modulation. Considering the reported broad-spectrum antiviral
potential of artemisinins, researchers are interested in whether
they could be used to combat COVID-19. We systematically
evaluated the anti-SARS-CoV-2 activities of nine
artemisinin-related compounds
in vitro
and
carried out a time-of-drug-addition assay to explore their
antiviral mode of action. Finally, a pharmacokinetic prediction
model was established to predict the therapeutic potential of
selected compounds against COVID-19. Arteannuin B showed the
highest anti-SARS-CoV-2 potential with an EC
50
of
10.28 ± 1.12 μM. Artesunate and dihydroartemisinin
showed similar EC
50
values of 12.98 ± 5.30
μM and 13.31 ± 1.24 μM, respectively, which
could be clinically achieved in plasma after intravenous
administration. Interestingly, although an EC
50
of
23.17 ± 3.22 μM was not prominent among the tested
compounds, lumefantrine showed therapeutic promise due to high
plasma and lung drug concentrations after multiple dosing.
Further mode of action analysis revealed that arteannuin B and
lumefantrine acted at the post-entry step of SARS-CoV-2
infection. This research highlights the anti-SARS-CoV-2
potential of artemisinins and provides leading candidates for
anti-SARS-CoV-2 drug research and development. The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC50 values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC50 of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development. The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC50 values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC50 of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development.The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds in vitro and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC50 of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC50 values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC50 of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development. The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the global COVID-19 pandemic. Artemisinin, an old antimalarial drug derived from Chinese herbs, has saved millions of lives. Artemisinins are a cluster of artemisinin-related drugs developed for the treatment of malaria and have been reported to have multiple pharmacological activities, including anticancer, antiviral, and immune modulation. Considering the reported broad-spectrum antiviral potential of artemisinins, researchers are interested in whether they could be used to combat COVID-19. We systematically evaluated the anti-SARS-CoV-2 activities of nine artemisinin-related compounds and carried out a time-of-drug-addition assay to explore their antiviral mode of action. Finally, a pharmacokinetic prediction model was established to predict the therapeutic potential of selected compounds against COVID-19. Arteannuin B showed the highest anti-SARS-CoV-2 potential with an EC of 10.28 ± 1.12 μM. Artesunate and dihydroartemisinin showed similar EC values of 12.98 ± 5.30 μM and 13.31 ± 1.24 μM, respectively, which could be clinically achieved in plasma after intravenous administration. Interestingly, although an EC of 23.17 ± 3.22 μM was not prominent among the tested compounds, lumefantrine showed therapeutic promise due to high plasma and lung drug concentrations after multiple dosing. Further mode of action analysis revealed that arteannuin B and lumefantrine acted at the post-entry step of SARS-CoV-2 infection. This research highlights the anti-SARS-CoV-2 potential of artemisinins and provides leading candidates for anti-SARS-CoV-2 drug research and development. |
| Author | Xu, Mingyue Wang, Manli Cao, Ruiyuan Zhang, Huanyu Li, Wei Guo, Xiaojia Hu, Hengrui Zhao, Lei Xiao, Dian Li, Yuexiang Yan, Yunzheng Hu, Zhihong Yang, Jingjing Liu, Jia Zhang, Tianhong Zhong, Wu Li, Yufeng Wang, Xi |
| AuthorAffiliation | Guoke Excellence (Beijing) Medicine Technology Research Co., Ltd National Engineering Research Center for the Emergency Drug University of the Chinese Academy of Sciences State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science |
| AuthorAffiliation_xml | – name: Guoke Excellence (Beijing) Medicine Technology Research Co., Ltd – name: University of the Chinese Academy of Sciences – name: National Engineering Research Center for the Emergency Drug – name: State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science |
| Author_xml | – sequence: 1 givenname: Ruiyuan surname: Cao fullname: Cao, Ruiyuan organization: National Engineering Research Center for the Emergency Drug – sequence: 2 givenname: Hengrui surname: Hu fullname: Hu, Hengrui organization: University of the Chinese Academy of Sciences – sequence: 3 givenname: Yufeng surname: Li fullname: Li, Yufeng organization: University of the Chinese Academy of Sciences – sequence: 4 givenname: Xi surname: Wang fullname: Wang, Xi organization: State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science – sequence: 5 givenname: Mingyue surname: Xu fullname: Xu, Mingyue organization: University of the Chinese Academy of Sciences – sequence: 6 givenname: Jia surname: Liu fullname: Liu, Jia organization: State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science – sequence: 7 givenname: Huanyu surname: Zhang fullname: Zhang, Huanyu organization: University of the Chinese Academy of Sciences – sequence: 8 givenname: Yunzheng surname: Yan fullname: Yan, Yunzheng organization: National Engineering Research Center for the Emergency Drug – sequence: 9 givenname: Lei surname: Zhao fullname: Zhao, Lei organization: National Engineering Research Center for the Emergency Drug – sequence: 10 givenname: Wei surname: Li fullname: Li, Wei organization: National Engineering Research Center for the Emergency Drug – sequence: 11 givenname: Tianhong surname: Zhang fullname: Zhang, Tianhong organization: Guoke Excellence (Beijing) Medicine Technology Research Co., Ltd – sequence: 12 givenname: Dian surname: Xiao fullname: Xiao, Dian organization: National Engineering Research Center for the Emergency Drug – sequence: 13 givenname: Xiaojia surname: Guo fullname: Guo, Xiaojia organization: National Engineering Research Center for the Emergency Drug – sequence: 14 givenname: Yuexiang surname: Li fullname: Li, Yuexiang organization: National Engineering Research Center for the Emergency Drug – sequence: 15 givenname: Jingjing surname: Yang fullname: Yang, Jingjing organization: National Engineering Research Center for the Emergency Drug – sequence: 16 givenname: Zhihong orcidid: 0000-0002-1560-0928 surname: Hu fullname: Hu, Zhihong email: huzh@wh.iov.cn organization: State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science – sequence: 17 givenname: Manli surname: Wang fullname: Wang, Manli email: wangml@wh.iov.cn organization: State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science – sequence: 18 givenname: Wu orcidid: 0000-0002-0536-620X surname: Zhong fullname: Zhong, Wu email: zhongwu@bmi.ac.cn organization: National Engineering Research Center for the Emergency Drug |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32786284$$D View this record in MEDLINE/PubMed |
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| Snippet | The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the... The discovery of novel drug candidates with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is critical for the control of the... |
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| SubjectTerms | Animals Antimalarials - pharmacology Antiviral Agents - pharmacology Artemisinins - pharmacology Betacoronavirus - drug effects Chlorocebus aethiops Coronavirus Infections - drug therapy Coronavirus Infections - virology COVID-19 Drug Discovery Drug Repositioning Drugs, Chinese Herbal - pharmacology Pandemics Pneumonia, Viral - drug therapy Pneumonia, Viral - virology SARS-CoV-2 Vero Cells |
| Title | Anti-SARS-CoV‑2 Potential of Artemisinins In Vitro |
| URI | http://dx.doi.org/10.1021/acsinfecdis.0c00522 https://www.ncbi.nlm.nih.gov/pubmed/32786284 https://www.proquest.com/docview/2434054006 https://pubmed.ncbi.nlm.nih.gov/PMC7437450 |
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