Drug repositioning: A bibliometric analysis

Drug repurposing has become an effective approach to drug discovery, as it offers a new way to explore drugs. Based on the Science Citation Index Expanded (SCI-E) and Social Sciences Citation Index (SSCI) databases of the Web of Science core collection, this study presents a bibliometric analysis of drug repurposing publications from 2010 to 2020. Data were cleaned, mined, and visualized using Derwent Data Analyzer (DDA) software. An overview of the history and development trend of the number of publications, major journals, major countries, major institutions, author keywords, major contributors, and major research fields is provided. There were 2,978 publications included in the study. The findings show that the United States leads in this area of research, followed by China, the United Kingdom, and India. The Chinese Academy of Science published the most research studies, and NIH ranked first on the h-index. The Icahn School of Medicine at Mt Sinai leads in the average number of citations per study. Sci Rep, Drug Discov. Today, and Brief. Bioinform. are the three most productive journals evaluated from three separate perspectives, and pharmacology and pharmacy are unquestionably the most commonly used subject categories. Cheng, FX;Mucke, HAM;and Butte, AJ are the top 20 most prolific and influential authors. Keyword analysis shows that in recent years, most research has focused on drug discovery/drug development, COVID-19/SARS-CoV-2/coronavirus, molecular docking, virtual screening, cancer, and other research areas. The hotspots have changed in recent years, with COVID-19/SARS-CoV-2/coronavirus being the most popular topic for current drug repurposing research.

A decoy microrobot that removes SARS-CoV-2 and its variants in wastewater.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can persist in wastewater for several days, has a risk of waterborne-human transmission. The emergence of SARS-CoV-2 variants with increased infection capacity further highlights the need to remove the virus and restrict its spread in wastewater. Here, we report a decoy microrobot created by camouflaging algae with cell membranes displaying angiotensin-converting enzyme 2 (ACE2) for effective elimination of SARS-CoV-2 and its variants. The decoy microrobots show fast self-propulsion (>85 µm/s), allowing for successful "on-the-fly" elimination of SARS-CoV-2 spike proteins and pseudovirus in wastewater. Moreover, relying on the robust binding between ACE2 and SARS-CoV-2 variants, the decoy microrobots exhibit a broad-spectrum elimination of virus with a high efficiency of 95% for the wild-type strain, 92% for the Delta variant, and 93% for the Omicron variant, respectively. Our work presents a simple and safe decoy microrobot aimed toward eliminating viruses and other environmental hazards from wastewater.

Integration and Reanalysis of Four RNA-Seq Datasets Including BALF, Nasopharyngeal Swabs, Lung Biopsy, and Mouse Models Reveals Common Immune Features of COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1ß and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

Genomic Evolution and Variation of SARS-CoV-2 in the Early Phase of COVID-19 Pandemic in Guangdong Province, China.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) with unknown origin spread rapidly to 222 countries, areas or territories. To investigate the genomic evolution and variation in the early phase of COVID-19 pandemic in Guangdong, 60 specimens of SARS-CoV-2 were used to perform whole genome sequencing, and genomics, amino acid variation and Spike protein structure modeling analyses. Phylogenetic analysis suggested that the early variation in the SARS-CoV-2 genome was still intra-species, with no evolution to other coronaviruses. There were one to seven nucleotide variations (SNVs) in each genome and all SNVs were distributed in various fragments of the genome. The Spike protein bound with human receptor, an amino acid salt bridge and a potential furin cleavage site were found in the SARS-CoV-2 using molecular modeling. Our study clarified the characteristics of SARS-CoV-2 genomic evolution, variation and Spike protein structure in the early phase of local cases in Guangdong, which provided reference for generating prevention and control strategies and tracing the source of new outbreaks.

Capturing Cytokines with Advanced Materials: A Potential Strategy to Tackle COVID-19 Cytokine Storm.

The COVID-19 pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great impact on the global economy and people's daily life. In the clinic, most patients with COVID-19 show none or mild symptoms, while approximately 20% of them develop severe pneumonia, multiple organ failure, or septic shock due to infection-induced cytokine release syndrome (the so-called "cytokine storm"). Neutralizing antibodies targeting inflammatory cytokines may potentially curb immunopathology caused by COVID-19; however, the complexity of cytokine interactions and the multiplicity of cytokine targets make attenuating the cytokine storm challenging. Nonspecific in vivo biodistribution and dose-limiting side effects further limit the broad application of those free antibodies. Recent advances in biomaterials and nanotechnology have offered many promising opportunities for infectious and inflammatory diseases. Here, potential mechanisms of COVID-19 cytokine storm are first discussed, and relevant therapeutic strategies and ongoing clinical trials are then reviewed. Furthermore, recent research involving emerging biomaterials for improving antibody-based and broad-spectrum cytokine neutralization is summarized. It is anticipated that this work will provide insights on the development of novel therapeutics toward efficacious management of COVID-19 cytokine storm and other inflammatory diseases.

Brief Report: Retrospective Evaluation on the Efficacy of Lopinavir/Ritonavir and Chloroquine to Treat Nonsevere COVID-19 Patients.

BACKGROUND: The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified. METHODS: We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared. RESULTS: Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups. CONCLUSIONS: Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.

Specific dynamic variations in the peripheral blood lymphocyte subsets in COVID-19 and severe influenza A patients: a retrospective observational study.

BACKGROUND: Both COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. METHODS: By retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1-4). RESULTS: We reviewed the patients' data of 94 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 37 severe influenza A. We found total lymphocytes (0.81 × 109/L vs 1.74 × 109/L, P = 0.001; 0.87 × 109/L vs 1.74 × 109/L, P < 0.0001, respectively) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of severe COVID-19 and severe influenza A patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). CONCLUSIONS: Our study suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.

Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.

Clinical Characteristics and Risk Factors of Acute Respiratory Distress Syndrome (ARDS) in COVID-19 Patients in Beijing, China: A Retrospective Study.

BACKGROUND Coronavirus disease 2019 (COVID-19) is a new infectious disease, and acute respiratory syndrome (ARDS) plays an important role in the process of disease aggravation. The detailed clinical course and risk factors of ARDS have not been well described. MATERIAL AND METHODS We retrospectively investigated the demographic, clinical, and laboratory data of adult confirmed cases of COVID-19 in Beijing Ditan Hospital from Jan 20 to Feb 29, 2020 and compared the differences between ARDS cases and non-ARDS cases. Univariate and multivariate logistic regression methods were employed to explore the risk factors associated with ARDS. RESULTS Of the 130 adult patients enrolled in this study, the median age was 46.5 (34-62) years and 76 (58.5%) were male. ARDS developed in 26 (20.0%) and 1 (0.8%) death occurred. Fever occurred in 114 patients, with a median highest temperature of 38.5 (38-39)°C and median fever duration of 8 (3-11) days. The median time from illness onset to ARDS was 10 (6-13) days, the median time to chest CT improvement was 17 (14-21) days, and median time to negative nucleic acid test result was 27 (17-33) days. Multivariate regression analysis showed increasing odds of ARDS associated with age older than 65 years (OR=4.75, 95% CL1.26-17.89, P=0.021), lymphocyte counts [0.5-1×109/L (OR=8.80, 95% CL 2.22-34.99, P=0.002); <0.5×109/L(OR=36.23, 95% CL 4.63-2083.48, P=0.001)], and temperature peak ≥39.1°C (OR=5.35, 95% CL 1.38-20.76, P=0.015). CONCLUSIONS ARDS tended to occur in the second week of the disease course. Potential risk factors for ARDS were older age (>65 years), lymphopenia (≤1.0×109/L), and temperature peak (≥39.1°C). These findings could help clinicians to predict which patients will have a poor prognosis at an early stage.

Balancing the decomposable behavior and wet tensile mechanical property of cellulose-based wet wipe substrates by the aqueous adhesive.

With the current global outbreak of novel coronaviruses, the fabrication of decomposable wet wipe with sufficient wet strength to meet daily use is promising but still challenging, especially when renewable cellulose was employed. In this work, a decomposable cellulose-based wet wipe substrate is demonstrated by introducing a synthetic N-vinyl pyrrolidone-glycidyl methacrylate (NVP-GMA) adhesive on the cellulose surface. Experimental results reveal that the NVP-GMA adhesive not only significantly facilitates the chemical bonding between cellulose fibers in the wet state, but also increase the surface wettability and water retention. The as-fabricated cellulose-based wet wipe substrate displays a superb water retention capacity of 1.9 times, an excellent water absorption capacity (completely wetted with 0° water contact angle), and a perfect wet tensile index of 3.32 N.m.g-1. It is far better than state-of-the-art wet toilet wipe on the market (non-woven). The prepared renewable and degradable cellulose-based substrate with excellent mechanical strength has potential application prospects in diverse commercially available products such as sanitary and medical wet wipes.

First Case of Coronavirus Disease 2019 in Childhood Leukemia in China.

We report the first case of coronavirus disease 2019 (COVID-19) comorbid with leukemia in a patient hospitalized in Beijing, China. The patient showed a prolonged manifestation of symptoms and a protracted diagnosis period of COVID-19. It is necessary to extend isolation time, increase the number of nucleic acid detections and conduct early symptomatic treatment for children with both COVID-19 and additional health problems.