In-Silico targeting of SARS-CoV-2 NSP6 for drug and natural products repurposing.

Non-Structural Protein 6 (NSP6) has a protecting role for SARS-CoV-2 replication by inhibiting the expansion of autophagosomes inside the cell. NSP6 is involved in the endoplasmic reticulum stress response by binding to Sigma receptor 1 (SR1). Nevertheless, NSP6 crystal structure is not solved yet. Therefore, NSP6 is considered a challenging target in Structure-Based Drug Discovery. Herein, we utilized the high quality NSP6 model built by AlphaFold in our study. Targeting a putative NSP6 binding site is believed to inhibit the SR1-NSP6 protein-protein interactions. Three databases were virtually screened, namely FDA-approved drugs (DrugBank), Northern African Natural Products Database (NANPDB) and South African Natural Compounds Database (SANCDB) with a total of 8158 compounds. Further validation for 9 candidates via molecular dynamics simulations for 100 ns recommended potential binders to the NSP6 binding site. The proposed candidates are recommended for biological testing to cease the rapidly growing pandemic.

The efficacy of local anesthetics in pain relief during colposcopic-guided biopsy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Colposcopy is an office gynecological procedure used for cervical evaluation in patients with abnormal cervical cytology. It is considered an important tool for early detection of cases of cervical cancer. OBJECTIVE: To evaluate the evidence from published randomized clinical trials (RCTs) about the efficacy of local anesthetics in pain relief during colposcopic-guided biopsy. DATA SOURCES: Several electronic databases included MEDLINE, EMBASE, Cochrane Library, ISI and Scopus were searched using the relevant MeSH terms. METHODS OF STUDY SELECTION: All RCTs assessing the effect of local anesthetics in relieving pain during colposcopy were considered for this meta-analysis. There were 1339 studies identified of which 11 studies deemed eligible for this review. We performed quality and risk of bias assessment for all included studies. DATA EXTRACTION: Three researchers independently extracted the data from the individual articles and entered it into RevMan software. The extracted outcomes included pain scores and the duration of the procedure. RESULTS: Eleven RCTs were included. Local anesthesia (LA) was associated with higher pain at speculum insertion than control (SMD = 0.23, 95% CI [0.03, 0.43]). While, LA significantly reduced biopsy pain than control (SMD= -0.57, 95% CI [-0.94, -0.20]). The overall pooled estimate showed no significant difference between LA and control regarding postprocedural pain, pain on endocervical curettage, pain expectancy, and overall pain scores. CONCLUSIONS: This meta-analysis suggests that local anesthetics are effective in pain relief during a colposcopic-guided biopsy; however there is no strong evidence to recommend its use in current practice.