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1.
Chin Med ; 17(1): 40, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1770556

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2. PURPOSE: In this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS's clinical efficacy and safety in COVID-19. METHODS: The antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients. RESULTS: The results showed that LS (2, 1, 0.5 µg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1ß, GRO, CCL-5, MCP-3, IP-10, IL-1α). CONCLUSION: LS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.

2.
J Thorac Dis ; 14(2): 355-370, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1737501

ABSTRACT

Background: The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19. Methods: We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels. Results: Eight pathogens, SARS-CoV-2, Aspergillus fumigatus (A. fumigatus), Mycoplasma orale (M. orale), Myroides odoratus (M. odoratus), Acinetobacter baumannii (A. baumannii), Candida tropicalis, herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens. Conclusions: For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.

3.
Front Microbiol ; 12: 801946, 2021.
Article in English | MEDLINE | ID: covidwho-1690426

ABSTRACT

China implemented stringent non-pharmaceutical interventions (NPIs) in spring 2020, which has effectively suppressed SARS-CoV-2. In this study, we utilized data from routine respiratory virus testing requests from physicians and examined circulation of 11 other respiratory viruses in Southern China, from January 1, 2018 to December 31, 2020. A total of 58,169 throat swabs from patients with acute respiratory tract infections (ARTIs) were collected and tested. We found that while the overall activity of respiratory viruses was lower during the period with stringent NPIs, virus activity rebounded shortly after the NPIs were relaxed and social activities resumed. Only influenza was effectively suppressed with very low circulation which extended to the end of 2020. Circulation of other respiratory viruses in the community was maintained even during the period of stringent interventions, especially for rhinovirus. Our study shows that NPIs against COVID-19 have different impacts on respiratory viruses.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315389

ABSTRACT

Background: Respiratory tract infections (RTIs) is the highest prevalent disease and southern china has a wide spectrum of respiratory pathogen. The aim of this work was to renew the epidemiology characteristics of respiratory pathogens found in children and adults with RTIs from 2018 to 2020 in southern China. Methods: : In this work, a total of 134,552 nasopharyngeal or throat swabs (patients from 407 hospitals) were analyzed, and fourteen respiratory viruses (Influenza A virus, influenza B virus, parainfluenza viruses, respiratory syncytial virus, adenovirus, human rhinovirus, human metapneumovirus, human Coronavirus, human bocavirus, enterovirus, cytomegalovirus, herpes simplex virus, mycoplasma pneumoniae and chlamydia pneumoniae) were detected using PCR/RT-PCR. Result: The most common respiratory pathogens in southern china were ADV (16.19%), RSV (15.48%), RHV (11.51%), IAV (10.93%), MP (8.95%), EBV (8.70%), PIV (7.67%), IBV (5.44%), with IAV and ADV as the most prevalent pathogens in adults (11.68%) and children (17.10%) respectively. In detail, ADV (16.30%) and RSV (18.93%) are most common in 0-4 years old, with IAV (16.68%), ADV (20.36%) in 5-14 years old, with EBV (7.48%, 8.74%), IAV (15.43, 9.76%) in 15-49y, 50-64y and IAV (7.37%), IBV (2.43%) in 65-105y. Over three years witnessed an increase in PDR of PIV in 0-4y, 5-14y and 65-105y, and RHV in 5-14y and 15-49y. In month distribution, the positive detection rate of pathogens in adults were generally lower than that in children except for EBV and majority of pathogens has shown a sharp decline in 2020. In Upper RTIs, 77.27% (17/ 22) of co-infected patients had infection to ADV, with poly-infection to ADV and RHV the highest (8/22). In Lower RTIs, the ADV infected patients showed that its co-infection rate to MP, PIV, RHV or RSV were 19.51% (48/246), 15.45% (38/246), 14.63% (36/246) and 14.63% (36/246) respectively. Only IAV, IBV and EBV were detected in co-infection patients with lower RTIs. Conclusion: IAV and ADV were the most important respiratory pathogen in adults and children respectively in southern Chin and cross-reactivity might exist between ADV, RHV, PIV and MP. These should be taken into consideration when they formulate the strategies for co-infection avoidance in patients.

5.
J Chem Inf Model ; 61(12): 5763-5773, 2021 12 27.
Article in English | MEDLINE | ID: covidwho-1608918

ABSTRACT

COVID-19 caused by a novel coronavirus (SARS-CoV-2) has been spreading all over the world since the end of 2019, and no specific drug has been developed yet. 3C-like protease (3CLpro) acts as an important part of the replication of novel coronavirus and is a promising target for the development of anticoronavirus drugs. In this paper, eight machine learning models were constructed using naïve Bayesian (NB) and recursive partitioning (RP) algorithms for 3CLpro on the basis of optimized two-dimensional (2D) molecular descriptors (MDs) combined with ECFP_4, ECFP_6, and MACCS molecular fingerprints. The optimal models were selected according to the results of 5-fold cross verification, test set verification, and external test set verification. A total of 5766 natural compounds from the internal natural product database were predicted, among which 369 chemical components were predicted to be active compounds by the optimal models and the EstPGood values were more than 0.6, as predicted by the NB (MD + ECFP_6) model. Through ADMET analysis, 31 compounds were selected for further biological activity determination by the fluorescence resonance energy transfer (FRET) method and cytopathic effect (CPE) detection. The results indicated that (+)-shikonin, shikonin, scutellarein, and 5,3',4'-trihydroxyflavone showed certain activity in inhibiting SARS-CoV-2 3CLpro with the half-maximal inhibitory concentration (IC50) values ranging from 4.38 to 87.76 µM. In the CPE assay, 5,3',4'-trihydroxyflavone showed a certain antiviral effect with an IC50 value of 8.22 µM. The binding mechanism of 5,3',4'-trihydroxyflavone with SARS-CoV-2 3CLpro was further revealed through CDOCKER analysis. In this study, 3CLpro prediction models were constructed based on machine learning algorithms for the prediction of active compounds, and the activity of potential inhibitors was determined by the FRET method and CPE assay, which provide important information for further discovery and development of antinovel coronavirus drugs.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Bayes Theorem , Fluorescence Resonance Energy Transfer , Humans , Protease Inhibitors/pharmacology
6.
Value in Health ; 2021.
Article in English | ScienceDirect | ID: covidwho-1559519

ABSTRACT

Objectives Most countries have adopted public activity intervention policies to control the coronavirus disease 2019 (COVID-19) pandemic. Nevertheless, empirical evidence of the effectiveness of different interventions on the containment of the epidemic was inconsistent. Methods We retrieved time-series intervention policy data for 145 countries from the Oxford COVID-19 Government Response Tracker from December 31, 2019, to July 1, 2020, which included 8 containment and closure policies. We investigated the association of timeliness, stringency, and duration of intervention with cumulative infections per million population on July 1, 2020. We introduced a novel counterfactual estimator to estimate the effects of these interventions on COVID-19 time-varying reproduction number (Rt). Results There is some evidence that earlier implementation, longer durations, and more strictness of intervention policies at the early but not middle stage were associated with reduced infections of COVID-19. The counterfactual model proved to have controlled for unobserved time-varying confounders and established a valid causal relationship between policy intervention and Rt reduction. The average intervention effect revealed that all interventions significantly decrease Rt after their implementation. Rt decreased by 30% (22%-41%) in 25 to 32 days after policy intervention. Among the 8 interventions, school closing, workplace closing, and public events cancellation demonstrated the strongest and most consistent evidence of associations. Conclusions Our study provides more reliable evidence of the quantitative effects of policy interventions on the COVID-19 epidemic and suggested that stricter public activity interventions should be implemented at the early stage of the epidemic for improved containment.

7.
Phytomedicine ; 95: 153874, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1560696

ABSTRACT

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) pose a huge threat to human public health, no specific treatment is available. Jinzhen granule (JZ) is a traditional eight ingredients-Chinese medicine with prominent efficacy for treating viral-induced diseases. However, little is known about the antiviral effect and mechanism of JZ against SARS-CoV-2 and HCoV-229E. PURPOSE: This study aimed to reveal the antiviral effects of JZ against SARS-CoV-2 and HCoV-229E, and to further explore the underlying mechanisms regulating the host immune response. METHODS: The chromatographic separation of JZ was performed using a Shimadzu analytical high-performance liquid chromatograph with UV detection and Alltech ELSD 2000ES. We conducted cytopathic effect (CPE) and plaque reduction assays to evaluate the antiviral effect of JZ. A lethal human angiotensin converting enzyme 2 (hACE2) transgenic mouse model of SARS-CoV-2 was established to determine the protective effect of JZ on mortality and lung virus titers. Real-time quantitative PCR assays were used to analyze the expression of proinflammatory cytokines in vitro and in vivo. Western blotting was further performed to determine the activities on regulating the nuclear factor kappa B (NF-κB)/MAPK pathway. Finally, mitochondrial membrane potential assays, flow cytometry analysis and western blotting were used to assess the anti-apoptotic potency toward HCoV-229E infection. RESULTS: The results showed that 13 chemical components were identified and five peaks were determined and quantitated (gallic acid 1.97 mg/g, baicalin 20.69 mg/g, glycyrrhizic acid 4.92 mg/g, hyodeoxycholic acid 4.86 mg/g, cholic acid 4.07 mg/g). We found that JZ exerted inhibitory potency against SARS-CoV-2 and HCoV-229E in vitro by using CPE and plaque reduction assays, and it was further found that JZ protected mice infected by SARS-CoV-2 from death and inhibited lung virus titers. JZ also significantly decreased the induction of inflammatory cytokines (IL-1α, IL-6, CCL-5 and MIP-1ß), similar to the observed in vitro effect. Moreover, JZ suppressed the release of inflammatory cytokines in vitro and it decreased the protein expression of p-p38 MAPK, p-JNK, p-NF-κB p65 and p-IκBα induced by HCoV-229E and increased the expression of IκBα. Notably, JZ significantly protected HCoV-229E-infected Huh-7 cells from mitochondrial damage and decreased apoptotic cells. The activation of the mitochondria-mediated apoptotic pathway was inhibited by JZ, as shown by the reduced expression of cleaved caspase-9, caspase-3 and p-PARP. CONCLUSIONS: In conclusion, JZ (gallic acid 1.97 mg/g, baicalin 20.69 mg/g, glycyrrhizic acid 4.92 mg/g, hyodeoxycholic acid 4.86 mg/g, cholic acid 4.07 mg/g) exhibited antiviral activities against SARS-CoV-2 and HCoV-229E by regulating the NF-κB/MAPK pathway and the mitochondria-mediated apoptotic pathway. These findings demonstrated the efficacy of JZ against CoVs and suggested JZ treatment as a novel clinical therapeutic strategy for COVID-19.


Subject(s)
Antiviral Agents , Coronavirus 229E, Human , Drugs, Chinese Herbal/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/pharmacology , COVID-19 , Coronavirus 229E, Human/drug effects , Humans , MAP Kinase Signaling System , Mice , NF-kappa B
8.
Cell Rep ; 37(12): 110126, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1556413

ABSTRACT

Previous studies have shown that the high mortality caused by viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus primarily results from complications of a cytokine storm. Therefore, it is critical to identify the key factors participating in the cytokine storm. Here we demonstrate that interferon-induced protein 35 (IFP35) plays an important role in the cytokine storm induced by SARS-CoV-2 and influenza virus infection. We find that the levels of serum IFP35 in individuals with SARS-CoV-2 correlates with severity of the syndrome. Using mouse model and cell assays, we show that IFP35 is released by lung epithelial cells and macrophages after SARS-CoV-2 or influenza virus infection. In addition, we show that administration of neutralizing antibodies against IFP35 considerably reduces lung injury and, thus, the mortality rate of mice exposed to viral infection. Our findings suggest that IFP35 serves as a biomarker and as a therapeutic target in virus-induced syndromes.


Subject(s)
COVID-19/blood , COVID-19/drug therapy , Influenza, Human/blood , Influenza, Human/drug therapy , Intracellular Signaling Peptides and Proteins/blood , Animals , Antibodies, Neutralizing/administration & dosage , Biomarkers/blood , COVID-19/pathology , COVID-19/physiopathology , Disease Models, Animal , Humans , Inflammation/metabolism , Influenza, Human/pathology , Lung/metabolism , Lung/pathology , Macrophages/metabolism , Macrophages/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Patient Acuity , SARS-CoV-2/physiology
10.
Pharmacol Res ; 172: 105820, 2021 10.
Article in English | MEDLINE | ID: covidwho-1531713

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enter the host cells through the interaction between its receptor binding domain (RBD) of spike glycoprotein with angiotensin-converting enzyme 2 (ACE2) receptor on the plasma membrane of host cell. Neutralizing antibodies and peptide binders of RBD can block viral infection, however, the concern of accessibility and affordability of viral infection inhibitors has been raised. Here, we report the identification of natural compounds as potential SARS-CoV-2 entry inhibitors using the molecular docking-based virtual screening coupled with bilayer interferometry (BLI). From a library of 1871 natural compounds, epigallocatechin gallate (EGCG), 20(R)-ginsenoside Rg3 (RRg3), 20(S)-ginsenoside Rg3 (SRg3), isobavachalcone (Ibvc), isochlorogenic A (IscA) and bakuchiol (Bkc) effectively inhibited pseudovirus entry at concentrations up to 100 µM. Among these compounds, four compounds, EGCG, Ibvc, salvianolic acid A (SalA), and isoliensinine (Isl), were effective in inhibiting SARS-CoV-2-induced cytopathic effect and plaque formation in Vero E6 cells. The EGCG was further validated with no observable animal toxicity and certain antiviral effect against SARS-CoV-2 pseudovirus mutants (D614G, N501Y, N439K & Y453F). Interestingly, EGCG, Bkc and Ibvc bind to ACE2 receptor in BLI assay, suggesting a dual binding to RBD and ACE2. Current findings shed some insight into identifications and validations of SARS-CoV-2 entry inhibitors from natural compounds.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Antiviral Agents/chemistry , Biological Products/chemistry , COVID-19/drug therapy , Enzyme Inhibitors/chemistry , SARS-CoV-2/enzymology , Spike Glycoprotein, Coronavirus/metabolism , Animals , Antiviral Agents/pharmacology , Binding, Competitive , Biological Products/pharmacology , Catechin/analogs & derivatives , Catechin/pharmacology , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Chalcones/pharmacology , Chlorogenic Acid/analogs & derivatives , Chlorogenic Acid/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Enzyme Inhibitors/pharmacology , Ginsenosides/pharmacology , Humans , Interferometry , Mice, Inbred C57BL , Molecular Dynamics Simulation , Phenols/pharmacology , Protein Binding
11.
Pathogens ; 10(11)2021 Nov 18.
Article in English | MEDLINE | ID: covidwho-1524101

ABSTRACT

Guangdong province, located in South China, is an important economic hub with a large domestic migrant population and was among the earliest areas to report COVID-19 cases outside of Wuhan. We conducted a cross-sectional, age-stratified serosurvey to determine the seroprevalence of antibodies against SARS-CoV-2 after the emergence of COVID-19 in Guangdong. We tested 14,629 residual serum samples that were submitted for clinical testing from 21 prefectures between March and June 2020 for SARS-CoV-2 antibodies using a magnetic particle based chemiluminescent enzyme immunoassay and validated the results using a pseudovirus neutralization assay. We found 21 samples positive for SARS-CoV-2 IgG, resulting in an estimated age- and sex-weighted seroprevalence of 0.15% (95% CI: 0.06-0.24%). The overall age-specific seroprevalence was 0.07% (95% CI: 0.01-0.24%) in persons up to 9 years old, 0.22% (95% CI: 0.03-0.79%) in persons aged 10-19, 0.16% (95% CI: 0.07-0.33%) in persons aged 20-39, 0.13% (95% CI: 0.03-0.33%) in persons aged 40-59 and 0.18% (95% CI: 0.07-0.40%) in persons ≥60 years old. Fourteen (67%) samples had pseudovirus neutralization titers to S-protein, suggesting most of the IgG-positive samples were true-positives. Seroprevalence of antibodies to SARS-CoV-2 was low, indicating that there were no hidden epidemics during this period. Vaccination is urgently needed to increase population immunity to SARS-CoV-2.

14.
Phytomedicine ; 93: 153808, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1472131

ABSTRACT

BACKGROUND: Qingwenjiere Mixture (QJM) is a traditional Chinese medicine (TCM) that has been shown to have remarkable clinical efficacy against COVID-19. However, little is known about the antiviral and anti-inflammatory activities of QJM against a wider range of human coronavirus (HCoV) strains. PURPOSE: The study aims to investigate the antiviral and anti-inflammatory activities of QJM, as well as the underlying mechanisms against HCoV infections. METHODS: The chemical compositions from QJM were analyzed by LC-MS. The inhibitory effect of QJM on infections of HCoV-OC43, HCoV-229E, HCoV-NL63, and SARS-CoV-2 was evaluated in HRT-18 cells, Huh7 cells, LLC-MK2 cells, and Vero-E6 cells, respectively, by using cytopathic effect (CPE) inhibition assay or RT-qPCR detection of viral n, s, or RdRp/Hel genes. The expression of pro-inflammatory cytokines induced by HCoV-OC43, HCoV-229E, and SARS-CoV-2, as well as the host ace2 gene was also determined by RT-qPCR assay. Furthermore, the expression of key molecules in the NF-κB/MAPKs signaling pathways was determined by western blot. RESULTS: In alcohol-extraction groups of QJM and reference decoction pieces, 53 similar ion peaks were identified, the majority of which were phenylpropanoids, iridoids, and flavonoids. In addition, QJM reduced CPE caused by HCoVs and the expression of viral n genes or N protein. Pretreatment with QJM also exerted inhibitory effect on viral n gene expression. QJM also inhibited the expression of RdRp/Hel and s genes of SARS-CoV-2, as well as the host ace2 gene. Besides, QJM markedly reduced virus-induced mRNA expression of a panel of pro-inflammatory cytokines, such as IL-6, CXCL-8/IL-8, CXCL-10/IP-10, CCL-5/RANTES, TNF-α, IFN-α, CCL-2/MCP-1, CXCL-9/MIG, and IL1-α. We further showed that QJM inhibited the phosphorylation of NF-κB p65, and JNK, ERK 1/2, and p38 MAPKs in HCoV-OC43-infected HRT-18 cells. CONCLUSIONS: QJM has broad antiviral and anti-inflammatory activity against both common and newly emerged HCoVs possibly by inhibiting the activation of key components in NF-κB/MAPKs signaling pathway. QJM also has a prevention effect against HCoV infections and inhibits the host receptor required for virus entry. These results indicate that QJM may have the therapeutic potential in the treatment of diseases caused by a broad range of HCoVs.


Subject(s)
COVID-19 , Coronavirus OC43, Human , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Humans , SARS-CoV-2
15.
Evid Based Complement Alternat Med ; 2021: 5547424, 2021.
Article in English | MEDLINE | ID: covidwho-1405240

ABSTRACT

BACKGROUND: Luofushan-Baicao Oil (LBO) is an essential oil-rich traditional Chinese medicine (TCM) formula that is commonly used to treat cold, cough, headache, sore throat, swelling, and pain. However, the anti-influenza activities of LBO and the underlying mechanism remain to be investigated. METHODS: The in vitro anti-influenza activity of LBO was tested with methyl thiazolyl tetrazolium (MTT) and plaque assays. The effects of LBO on the expressions of viral nucleoprotein and cytokines were evaluated. In the polyinosinic-polycytidylic acid- (Poly I: C-) induced inflammation model, the influences of LBO on the expression of cytokines and the activation of NF-κB P65 (P65) and interferon regulatory factor 3 (IRF3) were tested. After influenza A virus (IVA) infection, mice were administered with LBO for 5 days. The lung index, histopathologic change, the expression of viral protein, P65, and IRF3 in the lung tissue were measured. The levels of proinflammatory cytokines in serum were examined. RESULTS: In vitro, LBO could significantly inhibit the infection of IVA, decrease the formation of plaques, and reduce the expression of viral nucleoprotein and cytokines. LBO could also effectively downregulate the expression of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interferon-ß and the activation of P65 and IRF3 in Poly I:C-treated cells. In the IVA-infected mice model, inhalation of LBO with atomizer could decrease the lung index, alleviate the pathological injury in the lung tissue, and reduce the serum levels of IL-1ß and IL-6. LBO could significantly downregulate the expression of viral protein (nucleoprotein, PB2, and matrix 2 ion channel) and the phosphorylation of P65 and IRF3 in the lungs of mice. CONCLUSION: The therapeutic effects of LBO on treating influenza might result from the regulation of the immune response of IVA infection. LBO can be developed as an alternative therapeutic agent for influenza prevention.

18.
Pharmacol Res ; 158: 104850, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318927

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide through person-to-person contact, causing a public health emergency of international concern. At present, there is no specific antiviral treatment recommended for SARS-CoV-2 infection. Liu Shen capsule (LS), a traditional Chinese medicine, has been proven to have a wide spectrum of pharmacological properties, such as anti-inflammatory, antiviral and immunomodulatory activities. However, little is known about the antiviral effect of LS against SARS-CoV-2. Herein, the study was designed to investigate the antiviral activity of SARS-CoV-2 and its potential effect in regulating the host's immune response. The inhibitory effect of LS against SARS-CoV-2 replication in Vero E6 cells was evaluated by using the cytopathic effect (CPE) and plaque reduction assay. The number of virions of SARS-CoV-2 was observed under transmission electron microscope after treatment with LS. Proinflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. The results showed that LS could significantly inhibit SARS-CoV-2 replication in Vero E6 cells, and reduce the number of virus particles and it could markedly reduce pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Moreover, the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blot and it was found that LS could inhibit the expression of p-NF-κB p65, p-IκBα and p-p38 MAPK, while increasing the expression of IκBα. These findings indicate that LS could inhibit SARS-CoV-2 virus infection via downregulating the expression of inflammatory cytokines induced virus and regulating the activity of NF-κB/MAPK signaling pathway in vitro, making its promising candidate treatment for controlling COVID-19 disease.


Subject(s)
Betacoronavirus/drug effects , Complex Mixtures/pharmacology , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Signal Transduction/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19 , Cell Proliferation/drug effects , Cells, Cultured , Chlorocebus aethiops , Coronavirus Infections/virology , Humans , Inflammation Mediators/metabolism , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Virion/drug effects
19.
J Ethnopharmacol ; 279: 114367, 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1281457

ABSTRACT

BACKGROUND: Although the rapid emergence of coronavirus disease 2019 (COVID-19) poses a considerable threat to global public health, no specific treatment is available for COVID-19. ReDuNing injection (RDN) is a traditional Chinese medicine known to exert antibacterial, antiviral, antipyretic, and anti-inflammatory effects. In addition, RDN has been recommended in the diagnosis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated pneumonia by the National Health Council and the National Administration of Chinese Medicine. However, there is no information regarding its efficacy against COVID-19. AIM OF STUDY: This study was designed to determine the clinical efficacy of RDN in patients with COVID-19 and characterize its antiviral activity against SARS-CoV-2 in vitro. MATERIALS AND METHODS: A total of 50 adults with COVID-19 were included in this study, and the primary endpoint was recovery from clinical symptoms following 14 days of treatment. General improvements were defined as the disappearance of the major symptoms of infection including fever, fatigue, and cough. The secondary endpoints included the proportion of patients who achieved clinical symptom amelioration on days 7 and 10, time to clinical recovery, time to a negative nucleic acid test result, duration of hospitalization, and time to defervescence. Plaque reduction and cytopathic effect assays were also performed in vitro, and reverse-transcription quantitative PCR was performed to evaluate the expression of inflammatory cytokines (TNF-α, IP-10, MCP-1, IL-6, IFN-α, IFN-γ, IL-2 and CCL-5) during SARS-CoV-2 infection. RESULTS: The RDN group exhibited a shorter median time for the resolution of clinical symptoms (120 vs. 220 h, P < 0.0001), less time to a negative PCR test result (215 vs. 310 h, P = 0.0017), shorter hospitalization (14.8 vs. 18.5 days, P = 0.0002), and lower timeframe for defervescence (24.5 vs. 75 h, P = 0.0001) than the control group. In addition, time to improved imaging was also shorter in the RDN group than in the control group (6 vs.8.9 days, P = 0.0273); symptom resolution rates were higher in the RDN group than in the control group at 7 (96.30% vs. 39.13%, P < 0.0001) and 10 days (96.30% vs. 56.52%, P = 0.0008). No allergic reactions or anaphylactic responses were reported in this trial. RDN markedly inhibited SARS-CoV-2 proliferation and viral plaque formation in vitro. In addition, RDN significantly reduced inflammatory cytokine production in infected cells. CONCLUSIONS: RDN relieves clinical symptoms in patients with COVID-19 and reduces SARS-CoV-2 infection by regulating inflammatory cytokine-related disorders, suggestion that this medication might be a safe and effective treatment for COVID-19.


Subject(s)
COVID-19 , Cytokines/analysis , Drugs, Chinese Herbal , SARS-CoV-2 , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Nucleic Acid Testing/methods , Cell Line , China/epidemiology , Cytotoxicity Tests, Immunologic/methods , Drug Monitoring/methods , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Symptom Assessment/methods , Treatment Outcome
20.
Ann Palliat Med ; 10(5): 5146-5155, 2021 May.
Article in English | MEDLINE | ID: covidwho-1200420

ABSTRACT

BACKGROUND: Reduning injection is a traditional Chinese medicine (TCM) with known efficacy against a variety of viral infections, but there is no data about its efficacy against coronavirus disease 2019 (COVID-19). METHODS: To explore the efficacy and safety of Reduning injection in the treatment of COVID-19, a randomized, open-labeled, multicenter, controlled trial was conducted from 12 general hospitals between 2020.02.06 and 2020.03.23. Patients with COVID-19 who met the diagnostic criteria of the "Diagnosis and Treatment Program for Novel Coronavirus Infection Pneumonia (Trial Fifth Edition)". Patients were randomized to routine treatment with or without Reduning injection (20 mL/day for 14 days) (ChiCTR2000029589). The primary endpoint was the rate of achieving clinical symptom recovery on day 14 of treatment. RESULTS: There were 77 and 80 participants in the Reduning and control groups. The symptom resolution rate at 14 days was higher in the Reduning injection than in controls [full-analysis set (FAS): 84.4% vs. 60.0%, P=0.0004]. Compared with controls, the Reduning group showed shorter median time to resolution of the clinical symptoms (143 vs. 313.5 h, P<0.001), shorter to nucleic acid test turning negative (146.5 vs. 255.5 h, P<0.001), shorter hospital stay (14.1 vs. 18.1 days, P<0.001), and shorter time to defervescence (29 vs. 71 h, P<0.001). There was no difference in AEs (3.9% vs. 8.8%, P=0.383). CONCLUSIONS: This preliminary trial suggests that Reduning injection might be effective and safe in patients with symptomatic COVID-19.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Drugs, Chinese Herbal/adverse effects , Humans , Medicine, Chinese Traditional , SARS-CoV-2 , Treatment Outcome
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