ABSTRACT
Coronaviruses emerged three times in the last two decades and became a source of concern globally. Humulus lupulus plant has been used widely in medical science. Our objective in this study was to determine the effects of the crude extract of H. lupulus in inhibiting MERS-CoV and SARS-CoV-2 viruses' replication in vitro using Vero E6 cell lines and predict the antiviral activity of its identified compounds against the receptor binding (RBD) protein of both viruses in silico. We determined the concentration of the extract that induced less than 50% cell toxicity (CC50), and the antiviral activity based on IC50 and plaque reduction assay. We used molecular docking simulation to predict the potential of known active compounds in H. lupulus to inhibit the RBD protein. H. lupulus extract showed very low toxicity on Vero E6 cells with CC50= 23.25 µg/µL and antiviral activity toward MERS-CoV and SARS-CoV-2 with IC50= 0.18 and 0.9 µg/µL, respectively. The crude extract showed inhibition rate of 84.6% with MERS-CoV and 80% with SARS-CoV-2. In silico analysis predicted the compounds 5′-prenylxanthohumo, xanthogalenol, dehydrocycloxanthohumol hydrate, 6-prenylnaringenin, isoxanthohumol, catechin gallate, epicatechin gallate, 8-prenylnaringenin and xanthohumol to inhibit MERS-CoV and SARS-CoV-2 invasion of host cells by interfering with viral spike protein and the host cell receptor recognition process. Drug likeness and toxicity risk prediction analysis confirmed their capability as potential drugs. Based on our findings, isolation, purification and testing of the suggested active compounds could lead to novel anti-coronavirus drugs. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
ABSTRACT
Introduction: Unplanned removal of NGTs is common and associated with multiple complications.1 Methods used to secure these tubes may influence removal rates.2 Following national guidance,3 we confirmed tube placement by CXR. We used the text of CXR requests to estimate the rates of NGT placement and to see how these were influenced by changing how NGTs were secured. We also used similar methodology to review changes to CXR requests mentioning central lines (CVCs) and endotracheal tubes (ETT). Objectives: To see how CXR requests for NGT placement were influenced by changing the method used to secure these tubes. MethodsIn a 42 bedded mixed general and neurosurgical unit, in November 2019 we changed the method to secure NGTs from Hollister feeding tube attachment devices (Hollister, IL, USA)., to handcrafted slings made from Micropore (3M, MN, USA) 1.25cm Surgical Tape.4 The text of CXR requests between October 2017 and July 2021 were analysed for text associated with NGTs, CVCs and ETTs. The number of bed days was calculated for each month from October 2017 and CXR rates per 100 bed days were calculated. Mann-Whitney U tests were used to establish if CXR rates changed significantly after November 2019 and after admitting patients with COVID-19 in March 2020. Distributions are shown as medians with [IQR]. Results: There were 15239 CXRs, a median of 330 [IQR 303-357] CXRs requested a month. The fraction mentioning each device was: ETT: 8%, CVC: 13%, NGT: 38% (18% of these also mentioning another device). The rates per 100 patient days per month were: NGT pre-Nov 2019: 15.9 [15.0-16.4]. Post-Nov 2019 11.6 [10.1-12.7] (p<0.001), Nov 2019 to February 2020: 12.0 [8.0-13.3], vs Pre Nov 2019 p=0.008. For CVCs pre-March 2019: 4.1 (3.6-4.6) post March 2019: 5.2 (4.6-5.9) (p< 0.001) for ETTs pre-March 2019: 2.8 (2.0-3.3), post-March 2019: 3.1 (2.4-3.7). Changes in monthly rates are shown in the run chart in Figure 1. Conclusions: Changing the method of securing NGTs resulted in a reduction of CXR requests mentioning NGTs, reviewing CXR requests can be used to monitor NGT displacements. The rate of CVC requests increased following March 2020.
ABSTRACT
3,5-Di[(E)-arylidene]-1-[3-(4-methylpiperazin-1-yl)alkyl]piperidin-4-ones 7 a-k were synthesized through dehydrohalogenation of 1-(2-chloroacyl)piperidin-4-ones 5 a-k with N-methylpiperazine (6). High antiproliferation potencies were observed by most of the synthesized agents against both HCT116 (colon) and MCF7 (breast) cancer cell lines relative to the standard references (sunitinib and 5-fluorouracil). The synthesized agents are of dual activity against topoisomerases I and II alpha however, with higher efficacy against topoisomerase II alpha rather than topoisomerase I. Flow-cytometry cell cycle studies support the observed antiproliferation properties and exhibit the capability of 1-(2-chloroacetyl)-3,5-bis[(E)-4-chlorobenzylidene]piperidin-4-one (5 e) and 3,5-bis[(E)-4-bromobenzylidene]-1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-one (7 g) to arrest the HCT116 cell cycle progression at G1/S and G1 phases, respectively. Noticeable anti-SARS-CoV-2 properties were observed by many synthesized agents. 3,5-Bis[(E)-4-chlorobenzylidene]-1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-one (7 f) is the most effective anti-SARS-CoV-2 synthesized with high SI. Applicability of the highly effective candidates synthesized as antitumor and anti-SARS-CoV-2 is due to the safety observations against normal (RPE1 and VERO-E6) cells. QSAR models validated internally and externally, support their possibility for optimizing more hits/leads.
ABSTRACT
SARS CoV-2 is still considered a global health issue, and its threat keeps growing with the emergence of newly evolved strains. Despite the success in developing some vaccines as a protective measure, finding cost-effective treatments is urgent. Accordingly, we screened a number of phenolic natural compounds for their in vitro anti-SARS CoV-2 activity. We found sinapic acid (SA) selectively inhibited the viral replication in vitro with an half-maximal inhibitory concentration (IC<sub>50</sub>) value of 2.69 microg/mL with significantly low cytotoxicity (CC<sub>50</sub> = 189.3 microg/mL). Subsequently, we virtually screened all currently available molecular targets using a multistep in silico protocol to find out the most probable molecular target that mediates this compound's antiviral activity. As a result, the viral envelope protein (E-protein) was suggested as the most possible hit for SA. Further in-depth molecular dynamic simulation-based investigation revealed the essential structural features of SA antiviral activity and its binding mode with E-protein. The structural and experimental results presented in this study strongly recommend SA as a promising structural motif for anti-SARS CoV-2 agent development.