Background Indications for computed tomography (CT) in preoperative patients with thyroid cancer are still controversial. Purpose To determine the value of CT and ultrasonography (US) in preoperative lymph node assessment of patients with papillary thyroid carcinoma (PTC) according to primary tumor size. Material and Methods A total 453 patients with surgically proven PTC who underwent US and CT for preoperative evaluation in 2010 at our tertiary referral center were included. The diagnostic sensitivity, specificity, and accuracy of US, CT, and the combination of US and CT (US/CT) in the preoperative nodal assessment were compared. We performed subgroup analysis to compare the findings according to primary tumor size. Results In overall tumors, adding CT to US had greater sensitivity, lower specificity, and greater accuracy in predicting central lymph node metastasis (LNM) but lower accuracy in prediction of lateral LNM. In smaller cancers (≤1 cm), US alone had greater specificity and accuracy than CT alone or US/CT in predicting lateral LNM. In larger cancers (>1 cm), CT had greater sensitivity and accuracy than US in predicting central LNM, while US had greater specificity and accuracy than CT in predicting lateral LNM. There were no patients with smaller tumors who showed retropharyngeal and superior mediastinal LNM diagnosed by CT alone. Conclusion CT is superior to US for detecting central LNM in preoperative patients with PTCs > 1 cm. However, there are no benefits to adding CT to US to predict lateral LNM in small cancers (≤1 cm).
Since infection with severe acute respiratory syndrome CoV-2 (SARS-CoV-2) was first reported in Wuhan City, China in December 2019 (Wu et al., 2020;Zhou et al., 2020a), the pandemic coronavirus disease 2019 (COVID-19) has caused serious challenges for the public health and medical systems worldwide (https://covid19.who.int/). SARS-CoV-2 is an enveloped virus with a plus-stranded RNA genome (varies from 29.8 kb to 29.9 kb) and belongs to lineage B beta-coronaviruses (Khailany et al., 2020). SARS-CoV-2 maintains its structure with four major structural protein complexes: spike (S) glycoprotein, nucleocapsid (N) phosphoprotein, membrane (M) glycoprotein and small envelope (E) glycoprotein (Satarker and Nampoothiri, 2020). It is known that angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 S protein for mediating viral attachment/membrane fusion and that transmembrane protease serine 2 (TMPRSS2) contributes to viral entry into host cells (Datta et al., 2020;Matsuyama et al., 2020;Zeidler and Karpinski 2020). In this regard, the therapeutic strategy against SARS-CoV-2 infection targeting the entry process is directed towards the development of neu- 427The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.
Peptides are promising therapeutic agents for COVID‐19 because of their specificity, easy synthesis, and ability to be fine‐tuned. We previously demonstrated that a cell‐permeable peptide corresponding to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Spike C‐terminal domain (CD) inhibits the interaction between viral spike and nucleocapsid proteins that results in SARS‐CoV‐2 replication in vitro. Here, we used docking studies to design R‐t‐Spike CD(D), a more potent short cell‐penetrating peptide composed of all D‐form amino acids and evaluated its inhibitory effect against the replication of SARS‐CoV‐2 S clade and other variants. R‐t‐Spike CD(D) was internalized into Vero cells and Calu‐3 cells and suppressed the replication of SARS‐CoV‐2 S clade, delta variant, and omicron variant with higher potency than the original peptide. In hemizygous K18‐hACE2 mice, intratracheal administration of R‐t‐Spike CD(D) effectively delivered the peptide to the trachea and lungs, whereas intranasal administration delivered the peptide mostly to the upper respiratory system and stomach, and a small amount to the lungs. Administration by either route reduced viral loads in mouse lungs and turbinates. Furthermore, intranasally administered R‐t‐Spike CD(D) mitigated pathological change in the lungs and increased the survival of mice after infection with the SARS‐CoV‐2 S clade or delta variant. Our data suggest that R‐t‐Spike CD(D) has potential as a therapeutic agent against SARS‐CoV‐2 infection.
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