Abstract
Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 μg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 μM and 2.60 μM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 μM) and indigodole B (IC50 = 2.09 μM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection.
Highlights
Strobilanthes cusia (Nees) Kuntze is a member of the family Acanthaceae, widely distributed in northeast India, Bangladesh, southern China, the Himalayan region, Myanmar, and Taiwan [1]
This study explored the anti-HCoV-NL63 activity exhibited by the methanol extract of S. cusia leaf and its major chemical components, including β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B, by means of cytopathic effect (CPE), virus yield, infectivity, time-of-addition/removal, and virucidal activity assays
The results revealed that the S. cusia leaf methanol extract exhibited a potent antiviral activity against HCoV-NL63
Summary
Strobilanthes cusia (Nees) Kuntze is a member of the family Acanthaceae, widely distributed in northeast India, Bangladesh, southern China, the Himalayan region, Myanmar, and Taiwan [1]. S. cusia root and leaf extracts have been used extensively as a traditional herbal medicine with anti-inflammatory, antipyretic, antimicrobial, and antiviral activities [2,3]. Several bioactive components from the S. cusia root, including strobilanthes A, 3H-benzoxazolinone, and aurantiamide acetate, have exhibited antiviral activity against influenza A and hepatitis B virus infections [5,6]. The S. cusia leaf (called “Da-Ching-Yeh” in Chinese) is generally used for the production of indigo dyes (Indigo Natruralis, named “Qing Dai” in Chinese), displaying antibacterial, anti-inflammatory, and antipyretic properties [7,8]. S. cusia leaves contain effective chemical components with antibacterial, anti-inflammatory and antitumor activities, including β-sitosterol, indirubin, tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline), betulin, indigodole A, indigodole B (5aR-ethyltryptanthrin), strobilanthosides A–C, and phenylethanoidglycosides [9,10]. The antiviral capability of S. cusia leaf extract is yet to be elucidated; clarifying its properties will prove to be relevant to respiratory virus infections
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