Lianhua Qingwen for COVID-19

BackgroundChinese herbal medicine (CHM) formulas played an important role during the pandemic of coronavirus disease 2019 (COVID-19). Many randomized controlled trials (RCTs) on CHM for COVID-19 were quickly published. Concerns have been raised about their quality. In addition, inadequate detailed information on CHM formula intervention may arouse suspicion about their effectiveness. We aim to assess the most recent evidence of the methodological reporting quality of these RCTs with strict randomization, and the precise reporting of the CHM formula intervention.MethodsRCTs on CHM formulas for COVID-19 were searched from nine databases. The CONSORT 2010, CONSORT-CHM Formulas 2017, and risk of bias were the guidelines used to assess the included RCTs. The checklist of sub-questions based on CONSORT-CHM Formulas 2017 was used to evaluate the precise reporting of CHM formula intervention. A comparison was made between RCTs that enrolled participants during and after the first wave of the pandemic (defined here as December 2019 to March 2020).ResultsThe average score for 66 studies evaluated based on three guidelines, the CONSORT 2010, the CONSORT-CHM Formulas 2017, and the checklist of sub-questions based on the CONSORT-CHM Formulas 2017, is 16.4, 15.2, and 17.2, respectively. The reporting rate of sample size calculation, allocation concealment, and blinding is less than 30%. The checklist of sub-questions based on the CONSORT-CHM formulas 2017 can help report and assess CHM formula intervention more precisely. Most studies assessed an “unclear risk of bias” due to insufficient information. RCTs published in English and recruited subjects during the first wave of the pandemic have a higher risk of participant blinding bias than the studies recruited subjects after that (P < 0.05).ConclusionThe methodological reporting quality in strictly randomized RCTs on CHM formulas for COVID-19 is inadequate—the reporting of sample size calculation, allocation concealment, and blinding need to improve especially. The checklist of sub-questions based on CONSORT-CHM formulas 2017 can help report and assess CHM formula intervention more precisely. The methodological reporting quality of RCTs published in English and enrolled participants during the first wave of the pandemic is worse than the studies that recruited subjects after the first wave of the pandemic.

BackgroundTraditional Chinese medicine has been used for Coronavirus disease 2019 (COVID-19) as a therapeutic option. Lianhuaqingwen capsules (LHQW) are well-recognized for their efficacy, while Kegan Liyan oral liquid (KGLY), widely used for influenza treatment, has emerged as a promising candidate for COVID-19 therapy. This trial aims to assess whether KGLY is non-inferior to LHQW in treating mild COVID-19.MethodsA total of 127 participants (63 in KGLY group and 64 in LHQW group) were randomly allocated to receive either KGLY therapy or LHQW therapy in a 1:1 ratio. The treatment was given for 7 days, and the follow-up period was 3 days.Outcome measuresThe primary outcome was symptom remission at day 10. Secondary outcomes included symptom recovery, time to symptom remission, recovery rates and time to recovery of selected symptoms, change in visual analog scale score for selected symptoms, area under the curve of the visual analog scale score for sore throat, negative conversion of the SARS-CoV-2 infection, having a positive test result after negative conversion, and incidence of pneumonia.ResultsFull analysis set analysis showed that the symptom remission rate at day 10 was 60.7% with KGLY and 58.3% in LHQW (difference + 2.3 p.p., lower limit of 95% confidence interval − 14.8 p.p.), indicating non-inferiority. There were no significant differences between the groups for any secondary outcome. The occurrence of adverse events did not differ between the groups and no severe adverse events were documented in either group.ConclusionBased on the study results, this trial proved that KGLY was non-inferior to LHQW for mild COVID-19, providing a promising option for COVID-19 treatment.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=166372, Identifier, [ChiCTR2200059105].

AbstractObjectiveCoronavirus disease‐2019 (COVID‐19) can cause not only respiratory symptoms but also facial paralysis. Lianhua Qingwen (LHQW) has been reported to have therapeutic effects on COVID‐19 and facial neuritis (FN). We explored the potential mechanism of LHQW in the treatment of COVID‐19 and FN through a network‐pharmacology approach.MethodsActive compounds and relevant targets of LHQW were obtained from the databases of Traditional Chinese Medicine Systems Pharmacology Database, HERB, UniProt Knowledge Base, SwissADME, and Swiss Target Prediction. Disease targets of COVID‐19 and FN were acquired from Gene Cards. Database For Annotation, Visualization And Integrated Discovery and Metascape were used to search the biological functions of intersecting targets. After identifying the core targets and their corresponding ingredients, KEGG Mapper analyzes the localization of core targets in key pathways. AutoDock were employed to conduct molecular docking of the core targets and their corresponding ingredients.ResultsWe obtained four core genes: interleukin (IL)‐8, IL‐1B, IL‐6, and tumor necrosis factor (TNF)‐α. Database searching revealed the anti‐inflammatory and antiviral effects of LHQW may be related to the action of aleo‐emodin, hyperforin, kaempferol, luteolin, and quercetin on these four genes by regulating the pathways of IL‐17 and NOD‐like receptor. The molecular‐docking results of the four core targets and their corresponding active ingredients showed good binding activity between receptors and ligands.ConclusionsWe uncovered the active ingredients, potential targets, and biological pathways of LHQW for COVID‐19 and FN coinfection. Our data provide a theoretical basis for further exploration of the mechanism of action of LHQW in treatment of COVID‐19 and FN.

Abstract Background Traditional Chinese medicine (TCM) has developed a rich theoretical system and practical experience in fighting to infectious diseases over the past thousands of years, and has played an important role in controlling the spread owing to its unique advantages. In particular, its significant contribution to the prevention and control of Corona Virus Disease 2019 (COVID-19) is widely recognized. COVID-19 infection is mainly non-severe with a favorable overall outcome, but patients with comorbidities tend to have a poor prognosis. However, a comprehensive review of TCM for preventing and treating COVID-19 with comorbidities across various systems is still lacking. Hence, this scoping review aims to conduct a comprehensive investigation on treatment outcome of TCM for treating COVID-19 with comorbidities across various systems. Methods The scoping review was conducted by searching English databases including PubMed and Web of Science, and Chinese databases including China National Knowledge Infrastructure and Wanfang between January 2020 and January 2024. We followed the inclusion and exclusion criteria to identify relevant literature. Information for inclusion in the literature were subsequently extracted and consolidated. Results We enrolled 13 literature that met the inclusion criteria in the review finally. Our analysis revealed that research on COVID-19 with comorbidities was mostly focused on circulatory diseases, including hypertension, heart failure, and cerebrovascular diseases, most common comorbidities were hypertension. Followed by endocrine and metabolic diseases such as diabetes, respiratory diseases including pulmonary tuberculosis and chronic obstructive pulmonary disease have been also addressed. However, there were few studies on co-infectious urogenital system disease, and no studies on the rheumatic, immune, hematological, nervous, reproductive, and skin systems diseases. Based on existing studies, TCM has significantly improved the clinical symptoms of COVID-19 with comorbidities such as fever, fatigue, dry cough, anorexia and asthma, the absorption of lung lesions, shortened the duration of viral shedding and the course of disease. Conclusions TCM has great application prospects in treating COVID-19 with comorbidities. These findings could provide important evidence for clinicians to treat COVID-19 with comorbidities. Multi-center studies are required to confirm our results in the future. Graphical Abstract

Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks. Unveiling the genomic intricacies of SARS-CoV-2 variants, including the WHO-designated Omicron variant, we explore diverse antiviral categories such as fusion inhibitors, protease inhibitors, transcription inhibitors, neuraminidase inhibitors, nucleoside reverse transcriptase, and non-antiviral interventions like importin α/β1-mediated nuclear import inhibitors, neutralizing antibodies, and convalescent plasma. Notably, Molnupiravir emerges as a pivotal player, now licensed in the UK. This review offers a fresh perspective on the historical evolution of COVID-19 therapeutics, from repurposing endeavors to the latest developments in oral anti-SARS-CoV-2 treatments, ushering in a new era of hope in the battle against the pandemic.

Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks. Unveiling the genomic intricacies of SARS-CoV-2 variants, including the WHO-designated Omicron variant, we explore diverse antiviral categories such as Fusion inhibitors, Protease inhibitors, Transcription inhibitors, Neuraminidase inhibitors, Nucleoside reverse transcriptase, and non-antiviral interventions like Importin α/β1-mediated nuclear import inhibitors, Neutralizing antibodies and convalescent plasma. Notably, Molnupiravir emerges as a pivotal player, now licensed in the UK. This review offers a fresh perspective on the historical evolution of COVID-19 therapeutics, from repurposing endeavors to the latest developments in oral anti-SARS-CoV-2 treatments, ushering in a new era of hope in the battle against the pandemic.

Big data was utilized to analyze the network of biological systems and multi-target drug signal nodes, and despite traditional Chinese medicine proving effective against COVID-19 since the 2019 outbreak, the complexity and challenging actions of network pharmacology are essential for in-depth analysis. Objective: To present an overview of the literature on the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19 based on network pharmacology. Methods: A succinct explanation of the data sources: Twenty items in all were found after browsing the English and Chinese data websites. Following screening, data synthesis techniques and the remaining eight publications were located. Results: This study contained eight publications, including network pharmacology investigations on the mechanisms of action of eight prescription TCM medications. Many prescription drugs and specialty treatments from traditional Chinese medicine, including astragalus membranaceus-atractylodes rhizoma, LHQW, TJQWG, ephedra and glycyrrhiza, Yinqiao powder, rhizoma polygonati, MXSGD, and HSBDF, have been utilized in the clinical treatment of COVID-19. Their primary modes of action entail several components working on many targets and pathways related to immune modulation, organ protection, antiviral, and anti-inflammatory properties. Conclusion: This study reviewed eight Chinese herbal formulas used for treating COVID-19 and found they all contain quercetin, a compound that may reduce lung damage, and target at least one of TNF, IL-2, or IL-6, potentially decreasing inflammation and boosting immunity. All these traditional Chinese medicine (TCM) treatments were effective against COVID-19, offering valuable insights and inspiration for future drug research.

Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.

Abstract Background The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by the World Health Organization. However, a large population is still unvaccinated, leading to the emergence of mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from the World Health Organization raised concerns about the Omicron variant, which emerged in South Africa during a surge in COVID-19 cases in November 2021. Vaccines are not proven completely effective or safe against Omicron, leading to clinical trials for combating infection by the mutated virus. The absence of suitable pharmaceuticals has led scientists and clinicians to search for alternative and supplementary therapies, including dietary patterns, to reduce the effect of mutated strains. Main body This review analyzed Coronavirus aetiology, epidemiology, and natural products for combating Omicron. Although the literature search did not include keywords related to in silico or computational research, in silico investigations were emphasized in this study. Molecular docking was implemented to compare the interaction between natural products and Chloroquine with the ACE2 receptor protein amino acid residues of Omicron. The global Omicron infection proceeding SARS-CoV-2 vaccination was also elucidated. The docking results suggest that DGCG may bind to the ACE2 receptor three times more effectively than standard chloroquine. Conclusion The emergence of the Omicron variant has highlighted the need for alternative therapies to reduce the impact of mutated strains. The current review suggests that natural products such as DGCG may be effective in binding to the ACE2 receptor and combating the Omicron variant, however, further research is required to validate the results of this study and explore the potential of natural products to mitigate COVID-19. Graphical abstract

Abstract Background The etiological agent for the coronavirus illness outbreak in 2019–2020 is a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19), whereas coronavirus disease pandemic of 2019 (COVID-19) has compelled the implementation of novel therapeutic options. Main body of the abstract There are currently no targeted therapeutic medicines for this condition, and effective treatment options are quite restricted; however, new therapeutic candidates targeting the viral replication cycle are being investigated. The primary protease of the severe acute respiratory syndrome coronavirus 2 virus is a major target for therapeutic development (MPro). Severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus (MERS-CoV) all seem to have a structurally conserved substrate-binding domain that can be used to develop novel protease inhibitors. Short conclusion With the recent publication of the X-ray crystal structure of the severe acute respiratory syndrome coronavirus 2 Mm, virtual and in vitro screening investigations to find MPro inhibitors are fast progressing. The focus of this review is on recent advancements in the quest for small-molecule inhibitors of the severe acute respiratory syndrome coronavirus 2 main protease.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

Acute respiratory distress syndrome (ARDS) is intricately linked with SARS-CoV-2-associated disease severity and mortality, especially in patients with co-morbidities. Lung tissue injury caused as a consequence of ARDS leads to fluid build-up in the alveolar sacs, which in turn affects oxygen supply from the capillaries. ARDS is a result of a hyperinflammatory, non-specific local immune response (cytokine storm), which is aggravated as the virus evades and meddles with protective anti-viral innate immune responses. Treatment and management of ARDS remain a major challenge, first, because the condition develops as the virus keeps replicating and, therefore, immunomodulatory drugs are required to be used with caution. Second, the hyperinflammatory responses observed during ARDS are quite heterogeneous and dependent on the stage of the disease and the clinical history of the patients. In this review, we present different anti-rheumatic drugs, natural compounds, monoclonal antibodies, and RNA therapeutics and discuss their application in the management of ARDS. We also discuss on the suitability of each of these drug classes at different stages of the disease. In the last section, we discuss the potential applications of advanced computational approaches in identifying reliable drug targets and in screening out credible lead compounds against ARDS.

Many inflammatory mechanisms are involved in the pathophysiology of COVID-19 infection. COVID-19 inhibits IFN antiviral responses, so we should expect an out-of-control viral replication. “Cytokine storms” occur due to the over-production of pro-inflammatory cytokines after an influx of neutrophils and monocytes/macrophages and may be responsible for the immunopathology of the lung involvement. Several cascades have been reported in the activation process of NF-κB. In this paper, to find new therapeutic options for COVID-19 infection, we reviewed some natural products that could potentially inhibit the NF-κB pathway. We found that sevoflurane, quercetin, resveratrol, curcumin, KIOM-C, bergenin, garcinia kola, shenfu, piperlongumine, wogonin, oroxylin, plantamajoside, naringin, ginseng, kaempferol, allium sativum L, illicium henryi, isoliquiritigenin, lianhua qingwen, magnoflorine, and ma Huang Tang might be effective in inhibiting the NF-KB pathway. These natural products could be helpful in the control of COVID-19 infections. However, larger clinical trials are needed to ascertain the efficacy of these products fully.

During the outbreak of the novel coronavirus disease (COVID-19), the Chinese government took a series of public health measures to tackle the outbreak and recommended six traditional Chinese medicine (TCM) evolved formulas, collectively referred to as “3-drugs-3-formulas”, for the treatment. In this prospective article, we will discuss how these six formulas evolved from TCM and what their underlying mechanisms of actions may be by evaluating the historical usage of the component formulas, the potential targeted pathways for the individual herbs used by STAR (signal transduction activity response) database from our laboratory, and the pathogenesis of COVID-19. Five of the six recommended formulas are administered orally, while the sixth is taken as an injection. Five classic categories of herbs in the six formulas including “Qing-Re”, “Qu-Shi”, “Huo-Xue”, “Bu-Yi” and “Xing-Qi” herbs are used based on different stages of disease. All five oral formulas build upon the core formula Maxingshigan Decoction (MD) which has anti-inflammatory and perhaps antiviral actions. While MD can have some desired effects, it may not be sufficient to treat COVID-19 on its own; consequently, complementary classic formulas and/or herbs have been added to potentiate each recommended formula’s anti-inflammatory, and perhaps anti-renin-angiotensin system (RAS)-mediated bradykinin storm (RBS) and antiviral effects to address the unique medical needs for different stages of COVID-19. The key actions of these formulas are likely to control systemic inflammation and/or RBS. The usage of Chinese medicine in the six formulas is consistent with the pathogenesis of COVID-19. Thus, an integrative systems biology approach—combining botanical treatments of conventional antiviral, anti-inflammatory or anti-RBS drugs to treat COVID-19 and its complications – should be explored.