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Coronavirus disease 2019 (COVID-19) was caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes human angiotensin converting enzyme 2 (hACE2) as the cellular receptor of its spike glycoprotein (SP) to gain entry into cells. Consequently, we focused on the potential of repurposing clinically available drugs to block the binding of SARS-CoV-2 to hACE2 by utilizing a novel artificial-intelligence drug screening approach. Based on the structure of S-RBD and hACE2, the pharmacophore of SARS-CoV-2-receptor-binding-domain (S-RBD) -hACE2 interface was generated and used to screen a library of FDA-approved drugs. A total of 20 drugs were retrieved as S-RBD-hACE2 inhibitors, of which 16 drugs were identified to bind to S-RBD or hACE2. Notably, tannic acid was validated to interfere with the binding of S-RBD to hACE2, thereby inhibited pseudotyped SARS-CoV-2 entry. Experiments involving competitive inhibition revealed that tannic acid competes with S-RBD and hACE2, whereas molecular docking proved that tannic acid interacts with the essential residues of S-RBD and hACE2. Based on the known antiviral activity and our findings, tannic acid might serve as a promising candidate for preventing and treating SARS-CoV-2 infection.

Introduction: Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is widely used and often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China. In recent years, an elevated risk of allergic reactions has been observed following XYP, but whether concomitant medication use contributes to this risk is still unknown.Objective: This study aims to investigate the association between the concomitant use of XYP and the 25 most frequently co-applied medications with suspected allergic reactions for China’s patients receiving XYP.Methods: A nested case–control study was conducted using the sampling data from 2015 China’s Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with a 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day.Results: Out of 57,612 participants with XYP prescription, we obtained 949 matched case–control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin [OR = 4.29; 95% CI (2.52, 7.30)], cefoperazone-sulbactam [OR = 4.26; 95% CI (1.40, 13.01)], lidocaine [OR = 2.76; 95% CI (1.79, 4.25)], aminophylline [OR = 1.73; 95% CI (1.05, 2.85)], ribavirin [OR = 1.54; 95% CI (1.13, 2.10)], potassium chloride [OR = 1.45; 95% CI (1.10, 1.91)], and vitamin C [OR = 1.32; 95% CI (1.03, 1.70)] were associated with increased risk, while cefathiamidine [OR = 0.29; 95% CI (0.16, 0.51)] was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings.Conclusion: Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine, and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.

There has been growing recognition of the vital links between structural variations (SVs) and diverse diseases. Research suggests that, with much longer DNA fragments and abundant contextual information, long-read technologies have advantages in SV detection even in complex repetitive regions. So far, several pipelines for calling SVs from long-read sequencing data have been proposed and used in human genome research. However, the performance of these pipelines is still lack of deep exploration and adequate comparison. In this study, we comprehensively evaluated the performance of three commonly used long-read SV detection pipelines, namely PBSV, Sniffles and PBHoney, especially the performance on detecting the SVs in tandem repeat regions (TRRs). Evaluated by using a robust benchmark for germline SV detection as the gold standard, we thoroughly estimated the precision, recall and F1 score of insertions and deletions detected by the pipelines. Our results revealed that all these pipelines clearly exhibited better performance outside TRRs than that in TRRs. The F1 scores of Sniffles in and outside TRRs were 0.60 and 0.76, respectively. The performance of PBSV was similar to that of Sniffles, and was generally higher than that of PBHoney. In conclusion, our findings can be benefit for choosing the appropriate pipelines in real practice and are good complementary to the application of long-read sequencing technologies in the research of rare diseases.

The progression of intervertebral disc degeneration (IDD) is multifactorial with the senescence of nucleus pulposus (NP) cells and closely related to inflammation in NP cells. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone isolated from medicinal plants that has anti-inflammatory properties. Thus, DHE may have a therapeutic effect on the progression of IDD. In this study, NP cells were used to determine the appropriate concentration of DHE in vitro. The role of DHE in tumor necrosis factor-α (TNF-α)–induced activation of inflammatory signaling pathways and cellular senescence, together with anabolism and catabolism of extracellular matrix (ECM) in NP cells, was examined in vitro. The therapeutic effect of DHE in vivo was determined using a spinal instability model of IDD in mice. The TNF-α–induced ECM degradation and the senescence of NP cells were partially attenuated by DHE. Mechanistically, DHE inhibited the activation of NF-κB and MAPK inflammatory signaling pathways and ameliorated the senescence of NP cells caused by the activation of STING-TBK1/NF-κB signaling induced by TNF-α. Furthermore, a spinal instability model in mice demonstrated that DHE treatment could ameliorate progression of IDD. Together, our findings indicate that DHE can alleviate IDD changes and has a potential therapeutic function for the treatment of IDD.

Despite of the low occurrence rate in the entire genomes, de novo mutation is proved to be deleterious and will lead to severe genetic diseases via impacting on the gene function. Considering the fact that the traditional family based linkage approaches and the genome-wide association studies are unsuitable for identifying the de novo mutations, in recent years, several pipelines have been proposed to detect them based on the whole-genome or whole-exome sequencing data and were used for calling them in the rare diseases. However, how the performance of these variant calling pipelines on detecting the de novo mutations is still unexplored. For the purpose of facilitating the appropriate choice of the pipelines and reducing the false positive rate, in this study, we thoroughly evaluated the performance of the commonly used trio calling methods on the detection of the de novo single-nucleotide variants (DNSNVs) by conducting a comparative analysis for the calling results. Our results exhibited that different pipelines have a specific tendency to detect the DNSNVs in the genomic regions with different GC contents. Additionally, to refine the calling results for a single pipeline, our proposed filter achieved satisfied results, indicating that the read coverage at the mutation positions can be used as an effective index to identify the high-confidence DNSNVs. Our findings should be good support for the committees to choose an appropriate way to explore the de novo mutations for the rare diseases.