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1.
Nat Commun ; 13(1): 2766, 2022 05 19.
Article in English | MEDLINE | ID: covidwho-1927082

ABSTRACT

A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic effects of diverse small molecule drugs against coronaviruses for prophylaxis or treatment purposes, and the best combination reduced viral titer by over four orders of magnitude. Using lipid nanoparticle-mediated RNA delivery, we demonstrate that the Cas13d system can effectively treat infection from multiple variants of coronavirus, including Omicron SARS-CoV-2, in human primary airway epithelium air-liquid interface (ALI) cultures. Our study establishes CRISPR-Cas13 as a BSA which is highly complementary to existing vaccination and antiviral treatment strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Liposomes , Nanoparticles , SARS-CoV-2/genetics
2.
Bioengineered ; 13(3): 5480-5508, 2022 03.
Article in English | MEDLINE | ID: covidwho-1697594

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Plants, Medicinal/chemistry , SARS-CoV-2/drug effects , Antiviral Agents/isolation & purification , COVID-19/pathology , COVID-19/virology , China , Drugs, Chinese Herbal/isolation & purification , Herbal Medicine/methods , Humans , Medicine, Chinese Traditional/methods , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324187

ABSTRACT

Objective: After effective control of the 2019 Coronavirus Disease (COVID-19) in China, how to reopen the hospital and avoid the outbreak in the hospital is a problem that needs to be carefully considered. The aim of this descriptive study is to share the experience of prevention and emergency management in our hospital and cardiac intensive care units (CCU) when medical services were reopened after COVID-19 was under control.Methods and ResultsWe conducted a retrospective, descriptive and single-centre study. Management strategy and data were collected from the Second Xiangya Hospital of Central South University, Hunan and CCU. We have implemented some strategies to prevent the prevalence of covid-19 in hospitals while ensuring that more critical cardiac patients can be admitted to CCU. These measures are summarized as follows: 1. gradually expanding medical services;2. risk classification and routine strict screening of patients admitted to CCU;3. strengthening the management of hospitalized patients, accompanying person and medical staffs;4. strengthening screening and isolation of suspected cases of inpatients;5. other measures such as strengthening training of medical workers, protective equipment and environmental management, and so on.ConclusionWe share the experience of prevention and emergency management in our hospital and CCU when medical services were reopened after effective control of the COVID-19 epidemic and hope it will be helpful for cardiologist or critical care physician all around the world to continue to provide critical care in a safe and orderly manner.

4.
Front Immunol ; 12: 662465, 2021.
Article in English | MEDLINE | ID: covidwho-1337636

ABSTRACT

To systematically explore potential biomarkers which can predict disease severity in COVID-19 patients and prevent the occurrence or development of severe COVID-19, the levels of 440 factors were analyzed in patients categorized according to COVID-19 disease severity; including asymptomatic, mild, moderate, severe, convalescent and healthy control groups. Factor candidates were validated by ELISA and functional relevance was uncovered by bioinformatics analysis. To identify potential biomarkers of occurrence or development of COVID-19, patient sera from three different severity groups (moderate, severe, and critical) at three time points (admission, remission, and discharge) and the expression levels of candidate biomarkers were measured. Eleven differential factors associated with disease severity were pinpointed from 440 factors across 111 patients of differing disease severity. The dynamic changes of GDF15 reflect the progression of the disease, while the other differential factors include TRAIL R1, IGFBP-1, IGFBP-4, VCAM-1, sFRP-3, FABP2, Transferrin, GDF15, IL-1F7, IL-5Rα, and CD200. Elevation of white blood cell count, neutrophil count, neutrophil-lymphocyte ratio (NLR), Alanine aminotransferase and Aspartate aminotransferase, low lymphocyte and eosinophil counts in the severe group were associated with the severity of COVID-19. GDF15 levels were observed to be associated with the severity of COVID-19 and the dynamic change of GDF15 levels was closely associated with the COVID-19 disease progression. Therefore, GDF15 might serve as an indicator of disease severity in COVID-19 patients.


Subject(s)
Biomarkers/metabolism , COVID-19/immunology , Growth Differentiation Factor 15/metabolism , Inflammation Mediators/metabolism , SARS-CoV-2/physiology , Adult , Aged , Computational Biology , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Young Adult
5.
Cell Rep Med ; 2(4): 100245, 2021 04 20.
Article in English | MEDLINE | ID: covidwho-1155662

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and variants has led to significant mortality. We recently reported that an RNA-targeting CRISPR-Cas13 system, called prophylactic antiviral CRISPR in human cells (PAC-MAN), offered an antiviral strategy against SARS-CoV-2 and influenza A virus. Here, we expand in silico analysis to use PAC-MAN to target a broad spectrum of human- or livestock-infectious RNA viruses with high specificity, coverage, and predicted efficiency. Our analysis reveals that a minimal set of 14 CRISPR RNAs (crRNAs) is able to target >90% of human-infectious viruses across 10 RNA virus families. We predict that a set of 5 experimentally validated crRNAs can target new SARS-CoV-2 variant sequences with zero mismatches. We also build an online resource (crispr-pacman.stanford.edu) to support community use of CRISPR-Cas13 for broad-spectrum RNA virus targeting. Our work provides a new bioinformatic resource for using CRISPR-Cas13 to target diverse RNA viruses to facilitate the development of CRISPR-based antivirals.


Subject(s)
CRISPR-Cas Systems/genetics , RNA Viruses/genetics , RNA, Guide/metabolism , COVID-19/pathology , COVID-19/virology , Humans , RNA Virus Infections/pathology , RNA Virus Infections/virology , RNA Viruses/isolation & purification , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Species Specificity
6.
Journal of Modern Laboratory Medicine ; 35(4):94-96, 2020.
Article in Chinese | GIM | ID: covidwho-1073551

ABSTRACT

Objective: To explore the application value of peripheral blood lymphocytes and their subgroups in patients with novel coronavirus pneumonia (COVID-19).

7.
Int J Med Sci ; 18(1): 29-41, 2021.
Article in English | MEDLINE | ID: covidwho-994132

ABSTRACT

Rationale: Previous studies of coronavirus disease 2019 (COVID-19) were mainly focused on cross-sectional analysis. In this study, we sought to evaluate the dynamic changes of immunological and radiographic features, and the association with the outcome of pulmonary lesions in COVID-19 patients. Methods: Peripheral blood samples and radiographic data were collected longitudinally for up to 8 weeks from 158 laboratory-confirmed COVID-19 patients. The chest computed tomography (CT) scans were scored based on a semi-quantification assessment according to the extent of pulmonary abnormalities; the temporal change of the immunological and radiographic features was analyzed. Results: Compared with mild and moderate patients, severe patients had significantly decreased counts of lymphocytes, CD4+ T cells, CD8+ T cells, and CD19+ B cells but dramatically elevated counts of neutrophils and levels of interleukin (IL)-6. Sequential monitoring showed a sustained increase in lymphocytes counts and significantly decreased levels of IL-6 in severe patients during the disease course. Notably, patients with persistent pulmonary lesions (CT score ≥ 5 in week 8) showed high levels of IL-6 during the follow-up period, compared with those with recovery lesions (CT score < 5 in week 8). More importantly, the peak expression of IL-6 prior to the aggravated lung injury was mainly found in patients with persistent lesions, and multivariate analysis showed that IL-6 level upon admission was an independent factor associated with the persistent pulmonary injury. Conclusion: Prolonged elevation of IL-6 is associated with persistent pulmonary lesions in COVID-19 patients. Sequential monitoring and timely intervention of IL-6 may favor the clinical management of COVID-19.


Subject(s)
COVID-19/immunology , Interleukin-6/blood , Lung Injury/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/diagnostic imaging , Female , Humans , Longitudinal Studies , Lung Injury/diagnostic imaging , Lung Injury/virology , Lymphocyte Count , Male , Middle Aged , Radiography, Thoracic , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
8.
Cell ; 181(4): 865-876.e12, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-684968

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , CRISPR-Cas Systems , Influenza A Virus, H1N1 Subtype/drug effects , RNA, Viral/antagonists & inhibitors , A549 Cells , Antibiotic Prophylaxis/methods , Base Sequence , Betacoronavirus/genetics , Betacoronavirus/growth & development , COVID-19 , Clustered Regularly Interspaced Short Palindromic Repeats , Computer Simulation , Conserved Sequence , Coronavirus/drug effects , Coronavirus/genetics , Coronavirus/growth & development , Coronavirus Infections/drug therapy , Coronavirus Nucleocapsid Proteins , Coronavirus RNA-Dependent RNA Polymerase , Epithelial Cells/virology , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/growth & development , Lung/pathology , Lung/virology , Nucleocapsid Proteins/genetics , Pandemics , Phosphoproteins , Phylogeny , Pneumonia, Viral/drug therapy , RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2 , Viral Nonstructural Proteins/genetics
9.
Immunology ; 160(3): 261-268, 2020 07.
Article in English | MEDLINE | ID: covidwho-381740

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious severe acute respiratory syndrome coronavirus 2. The immunopathological characteristics of patients with COVID-19, either systemic or local, have not been thoroughly studied. In the present study, we analysed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells and natural killer cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. Interleukin-6 (IL-6), IL-10 and C-reactive protein were remarkably up-regulated in patients with severe COVID-19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-6, IL-10 and C-reactive protein are reliable indicators of severe COVID-19.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Aged , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Betacoronavirus/physiology , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Female , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Lymphocytes/pathology , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/pathology , T-Lymphocytes, Regulatory/pathology
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