Identification and Semisynthesis of (–)-Anisomelic Acid as an Oral Antiviral Agent against SARS-CoV-2 in Mice
(–)-Anisomelic acid (AA), isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-β-lactone motif. Cytopathic effect assays showed that the anti-SARS-CoV-2 effect of AA (IC50 = 4.3 μM) is comparable to that of remdesivir (IC50 = 2.1 μM), and more potent than that of molnupiravir (IC50 = 27.8 μM). Challenge studies in SARS-CoV-2-infected K18-hACE2 mice showed that orally administration of AA and remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of AA from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing AA-based novel ligands for selectively targeting proteins involved in viral infection..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
chemRxiv.org - (2021) vom: 24. Dez. Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yu, Hai-Xin [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.26434/chemrxiv-2021-fcb6z |
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| 520 | |a (–)-Anisomelic acid (AA), isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-β-lactone motif. Cytopathic effect assays showed that the anti-SARS-CoV-2 effect of AA (IC50 = 4.3 μM) is comparable to that of remdesivir (IC50 = 2.1 μM), and more potent than that of molnupiravir (IC50 = 27.8 μM). Challenge studies in SARS-CoV-2-infected K18-hACE2 mice showed that orally administration of AA and remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of AA from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing AA-based novel ligands for selectively targeting proteins involved in viral infection. | ||
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| 700 | 1 | |a Lee, Chien-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Wen-Lv |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuan-He |e verfasserin |4 aut | |
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| 700 | 1 | |a Quan, Jun-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lin-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Tzeng, Yew-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Zhen |e verfasserin |4 aut | |
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