Abstract

BackgroundLianhuaqingke (LHQK) has been approved for the treatment of acute tracheobronchitis and exerts a broad-spectrum antiviral effect in our previous study.MethodsAcute pneumonia caused by HCoV-229E was modeled in BALB/c mice. The anti-viral effect of LHQK was assessed by measuring the lung index and virus titer of lung tissues. The expression levels of pro-inflammatory cytokines in lung tissues and peripheral blood were measured by ELISA. The morphological changes of lung tissues were observed by H&E staining. The subsets of Th cells were assayed by the flow cytometry, including Th0, Th1, Th2, Treg, and Th17. The expression level of MUC5AC in 16HBE cells treated with TNFα was measured by ELISA. Immunofluorescence staining for β-IV tubulin was used to identify the airway epithelial ciliary in the condition-cultured RTE cells treated with TNFα. The direct antiviral effect of LHQK was assessed in vitro in Vero E6 infected by SARS-CoV-2, validated in vivo in the COVID-19 model of hACE2 transgenic mouse by detecting the lung index, the SARS-CoV-2 virus load, and the morphological changes of lung tissues.ResultsLHQK reduced the weight loss and the lung index by inhibiting the HCoV-229E replication and reducing the expression of pro-inflammatory cytokines in lung tissues. An assay for the Th cell subsets in peripheral blood revealed that LHQK could reduce the ratio of Th1/Th2 and increase the Treg/Th17 ratio in a dose-dependent way, which indicated that LHQK could coordinate the Th-mediated immune responses against the virus. In in vitro injury by TNFα, LHQK inhibited MUC5AC expression in 16HBE cells and increased the number of β-IV tubulin positive staining cells in the condition-cultured RTE cells. In the SARS-CoV-2-infected mice, LHQK could reduce weight loss, inhibit viral replication, and alleviate lung tissue damage.ConclusionsOur results demonstrate that LHQK exerts therapeutic effects on pneumonia caused by HCoVs (HCoV-229E and SARS-CoV-2) in mice, and that the anti-HCoV effects might depend on its immunomodulatory capacities. All these results suggest that LHQK serves as a potential adjuvant for anti-HCoV therapies.

Highlights

  • Lianhuaqingke (LHQK) has been approved for the treatment of acute tracheobronchitis and exerts a broad-spectrum antiviral effect in our previous study

  • The results proved that LHQK exerted anti-viral and anti-inflammatory effects to treat coronavirus pneumonia, making it promising as a novel strategy for controlling coronavirus infection in clinical practice

  • Compared with the model group, the bodyweight of Human coronaviruses (HCoVs)-229E-infected mice in the LHQW group significantly increased from day 2 after infection (P ≤ 0.05 or P ≤ 0.01), and the bodyweight of HCoV-229E-infected mice treated with LHQK at each dose significantly increased

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Summary

Introduction

Lianhuaqingke (LHQK) has been approved for the treatment of acute tracheobronchitis and exerts a broad-spectrum antiviral effect in our previous study. 7 known strains of coronaviruses, including the novel SARS-CoV-2 coronavirus, are infectious to humans. Depending on the severity of the viral infection, HCoVs are technically divided into two categories, mildly and highly pathogenic HCoVs. The mildly pathogenic HCoVs are known to cause mild upper respiratory symptoms, presumably contributing to 15–30% common cold in humans [3], and severe respiratory infections rarely occur in infants, elderly people, or immunocompromised patients [4]. The highly pathogenic HCoVs tend to lead to fatal respiratory failure and acute respiratory distress syndrome. It is becoming increasingly urgent to find a practical treatment for those known HCoVs or even for future reemergence or the novel emerging virus [7]

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