ABSTRACT
The novel coronavirus disease 2019 (COVID-19) has become a matter of international concern as the disease is spreading exponentially. Statistics showed that infected patients in China who received combined treatment of Traditional Chinese Medicine and modern medicine exhibited lower fatality rate and relatively better clinical outcomes. Both Lian-Hua-Qing-Wen Capsule (LHQWC) and Jin-Hua-Qing-Gan Granule (JHQGG) have been recommended by China Food and Drug Administration for the treatment of COVID-19 and have played a vital role in the prevention of a variety of viral infections. Here, we desired to analyze the broad-spectrum anti-viral capacities of LHQWC and JHQGG, and to compare their pharmacological functions for rational clinical applications. Based on literature mining, we found that both LHQWC and JHQGG were endowed with multiple antiviral activities by both targeting viral life cycle and regulating host immune responses and inflammation. In addition, from literature analyzed, JHQGG is more potent in modulating viral life cycle, whereas LHQWC exhibits better efficacies in regulating host anti-viral responses. When translating into clinical applications, oral administration of LHQWC could be more beneficial for patients with insufficient immune functions or for patients with alleviated symptoms after treatment with JHQGG.
ABSTRACT
Besides pathogen evading, Acute Lung Injury (ALI), featuring the systematic inflammation and severe epithelial damages, is widely believed to be the central non-infectious factor controlling the progression of infectious diseases. ALI is partly caused by host immune responses. Under the inspiration of unsuccessful treatment in COVID-19, recent insights into pathogen-host interactions are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. The interaction unit consisting of macrophages and the alveolar epithelial cells has recently revealed as the therapeutic basis targeting ALI. Lian Hua Qing Wen capsule is the most effective and commonly-used clinical formula in treating respiratory infection for thousands of years in China. However, little is known about its relevance with ALI, especially its protective role against ALI-induced alveolar tissue damages. Aiming to evaluate its contribution in antibiotics-integrating therapies, this study pharmacologically verified whether LHQW could alleviate lipopolysaccharide (LPS)-induced ALI and explore its potential mechanisms in maintaining the physiology of macrophage-epithelial unit. In ALI mouse model, the pathological parameters, including the anal temperature, inflammation condition, lung edema, histopathological structures, have all been systematically analyzed. Results consistently supported the effectiveness of the combined strategy for LHQW and low-dose antibiotics. Furthermore, we established the macrophages-alveolar epithelial cells co-culture model and firstly proved that LHQW inhibited LPS-induced ER stress and TRAIL secretion in macrophages, thereby efficiently protected epithelial cells against TRAIL-induced apoptosis. Mechanistically, results showed that LHQW significantly deactivated NF-κB and reversed the SOCS3 expression in inflammatory macrophages. Furthermore, we proved that the therapeutic effects of LHQW were highly dependent on JNK-AP1 regulation. In conclusion, our data proved that LHQW is an epithelial protector in ALI, implying its promising potential in antibiotic alternative therapy.
ABSTRACT
Coronaviruses (CoVs), a family of enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, unusually large RNA genome, and unique replication capability. CoVs are known to cause various potentially lethal human respiratory infectious diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the very recent coronavirus disease 2019 (COVID-19) outbreak. Unfortunately, neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs. Therefore, effective prevention and treatment medications against human coronavirus are in urgent need. In the past decades, many natural compounds have been reported to possess multiple biological activities, including antiviral properties. In this article, we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS, and discussed their potential use for the treatment of COVID-19.