Modulation of in Vitro SARS-CoV-2 Infection by Stephania tetrandra and Its Alkaloid Constituents.

Botanical natural products have been widely consumed for their purported usefulness against COVID-19. Here, six botanical species from multiple sources and 173 isolated natural product compounds were screened for blockade of wild-type (WT) SARS-CoV-2 infection in human 293T epithelial cells overexpressing ACE-2 and TMPRSS2 protease (293TAT). Antiviral activity was demonstrated by an extract from Stephania tetrandra. Extract fractionation, liquid chromatography-mass spectrometry (LC-MS), antiviral assays, and computational analyses revealed that the alkaloid fraction and purified alkaloids tetrandrine, fangchinoline, and cepharanthine inhibited WT SARS-CoV-2 infection. The alkaloids and alkaloid fraction also inhibited the delta variant of concern but not WT SARS-CoV-2 in VeroAT cells. Membrane permeability assays demonstrate that the alkaloids are biologically available, although fangchinoline showed lower permeability than tetrandrine. At high concentrations, the extract, alkaloid fractions, and pure alkaloids induced phospholipidosis in 293TAT cells and less so in VeroAT cells. Gene expression profiling during virus infection suggested that alkaloid fraction and tetrandrine displayed similar effects on cellular gene expression and pathways, while fangchinoline showed distinct effects on cells. Our study demonstrates a multifaceted approach to systematically investigate the diverse activities conferred by complex botanical mixtures, their cell-context specificity, and their pleiotropic effects on biological systems.

ILLUMINATING THE GAP: DEFINING CHILDCARE NEEDS FOR CANCER PATIENTS AND THEIR FAMILIES

Purpose: One in two Canadians will be diagnosed with cancer in their lifetime. With a growing proportion of patients under the age of 60, it is estimated that upwards of 25% of cancer patients are managing the demands of childbearing and parenting alongside their diagnosis. There is a paucity of research detailing how parents with cancer balance their needs with the needs of their children. This study aims to more completely define the childcare needs and perspectives of cancer patients with dependent children. Materials and Methods: Between December 2020 and February 2021, cancer patients at one major Canadian Cancer Centre, who identified as primary caregiver to at least 1 dependent (<18 years of age) were invited to partake in a survey study. The survey was developed through consultation with a multidisciplinary team and best survey practices, and consisted of 34 closed and open-ended questions designed to assess childcare needs and the experiences of cancer patients with dependent children. Specific questions were also designed to assess the impact of COVID-19 on childcare needs. Eligible participants were identified by a research assistant and presented the opportunity to complete an electronic or paper-based survey. This study was approved by the local Research Ethics Board. Results: As of February 2021, 42 patients had been contacted and 29 had completed the survey in full (69%) Participants were an average age of 44.7 years ± 4.8 years and 97% female (28/29). Twenty-two participants (76%) reported diagnoses of breast cancer. Participants reported caring for two (18/29), one (10/29), or three (1/29) children. The average age of participants' children was 8.4 years, and ranged from 8 months to 18 years. Fourteen participants (48%) indicated having to reschedule appointments due to issues with childcare (nine of 14 rescheduling 1-3 appt.;4/14, 4-6 appt.;one of 14, 10+ appt.). Additionally, 11 participants (38%) reported bringing their child or children to their appointments as a solution for issues with childcare (seven of 11 for 1-3 appt.;three of 11, 4-6 appt.;one of 11, 10+ appt.). Fourteen of 26 respondents (54%) indicated that balancing childcare throughout their cancer journey has had a moderate (eight of 26) or extreme (six of 26) impact on their stress levels. Sixty-one percent (17/28) reported that the COVID-19 Pandemic has impacted their childcare needs and impacted their stress levels moderately (10/17) or extremely (three of 17). Seventy-eight percent (21/27) reported that a flexible childcare service would allow them to more regularly attend their appointments. The preferred delivery of such a program was onsite (hospital or cancer centre) (13/20, 65%), followed by in-home (seven of 20, 35%). Narrative analysis noted themes of increased stress and childcare responsibilities associated with the COVID-19 Pandemic and reduction of childcare resources and support. Conclusions: These preliminary results indicate that childcare issues are broadly impactful for parents battling cancer. The lack of supportive childcare negatively impacts the emotional psychological well-being of patients and their children, as well as impacts system efficiency and treatment compliance. Survey accrual is continuing and complete findings will aid in defining the childcare needs and perspectives of parents with cancer, as well as highlight potential solutions to support these individuals.