A map of the SARS-CoV-2 RNA structurome.

SARS-CoV-2 has exploded throughout the human population. To facilitate efforts to gain insights into SARS-CoV-2 biology and to target the virus therapeutically, it is essential to have a roadmap of likely functional regions embedded in its RNA genome. In this report, we used a bioinformatics approach, ScanFold, to deduce the local RNA structural landscape of the SARS-CoV-2 genome with the highest likelihood of being functional. We recapitulate previously-known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a large reservoir of potential drug targets for RNA-binding small molecules. Results are enhanced via the re-analyses of publicly-available genome-wide biochemical structure probing datasets that are broadly in agreement with our models. Additionally, ScanFold was updated to incorporate experimental data as constraints in the analysis to facilitate comparisons between ScanFold and other RNA modelling approaches. Ultimately, ScanFold was able to identify eight highly structured/conserved motifs in SARS-CoV-2 that agree with experimental data, without explicitly using these data. All results are made available via a public database (the RNAStructuromeDB: https://structurome.bb.iastate.edu/sars-cov-2) and model comparisons are readily viewable at https://structurome.bb.iastate.edu/sars-cov-2-global-model-comparisons.

ICONIC: Impact of Covid-19 on Outcomes iN muscle Invasive bladder Cancer - preliminary Results from a prospective IBUS (International British Urological Society) led multicentre collaborative study

Introduction: The Covid-19 pandemic in the UK led to much un-certainty about the delivery of cancer services. A shift from established therapy (and its timing) in patients with Muscle invasive Bladder Cancer (MIBC) has potential deleterious consequences. To understand outcomes, we formed a collaborative to measure overall and diseasefree survival at 3-years in patients with non-metastatic MIBC (Figure 1) treated during the UK's first wave of Covid-19. Secondary aims included comparison between treatment modalities and pre-Covid controls. Patients and Methods: The collaborative included clinicians from 13 major centres, representing 3 UK nations. A prospective clinical audit, endorsed by the National Cancer Research Institute, was started to collect comprehensive data. MIBC patients discussed at the multidisciplinary meeting (MDM) between 1/3/2020-30/06/2020 were included. Results: At submission, data were available from 12 centres for 299 patients. The mean age was 69.3 years (27- 90), and there were 72 female and 227 male patients. Mean Charlson Co-morbidity Index was 5 (1-12). Preliminary analysis of available data indicate the following: MDM recommendations for (at least) 1 in 4 patients were deemed as being modified from standard practice. Twenty six patients received neoadjuvant chemotherapy. In total (from available data), 99 received radical radiotherapy and 146 underwent radical cystectomy (65 and 74 specified as open and robotic assisted, respectively). Preliminary analysis suggests that 1 in 3 patients had died within 1 year. Conclusions: Preliminary Results indicate that recommendations for MIBC patients were significantly altered consequent to the pandemic and mortality was high. Analyses towards endpoints are awaited.

Prevalence and Risk Factors of Covid-19 Mortality and its Impact on Social Life of Pakistani Population

Background: Currently, the world is in a challenging situation due to Covid-19. The ministry of health in Pakistan reported the first case of Covid-19 on 26th February 2020 in Karachi whereas on the same day in Islamabad, the second case was confirmed in Pakistan. Objective: To assess the prevalence and risk factors of covid-19 mortality and its impact on social life of Pakistani population Methodology: This retrospective study was carried out at the Department of Pathology, Gomal Medical College, Medical Teaching Institute, Dera Ismail Khan, Pakistan for a period of ten months from March 2021 to December 2021. All the data was taken from the hospital record to determine the prevalence and risk factors associated with the mortality of covid-19. For determining the influence of covid-19 on the social life, online survey was conducted. Data was entered and analyzed by using SPSS version 24. Results: In the current study, the overall prevalence of covid-19 was 6%. The most common risk factors associated with the covid-19 was Diabetes mellitus in 25 (71.43%) subjects, hypertension in 22 (62.86%), ischemic heart disease in 16 (45.71%) while chronic liver disease was observed in 3 (8.57%) subjects. According to the survey, 420 (70%) participants thought that covid-19 will be controlled worldwide while 450 (75%) subjects thought that covid-19 will be controlled in Pakistan. Worry of contracting covid-19 even with protective measures was observed in 420 (70%) subjects. Conclusion: Our study reported that the prevalence of covid-19 was 6%. Diabetes mellitus, hypertension and ischemic heart disease were the major associated risk factors with the mortality of covid-19 and the overall impact of covid-19 on social life of Pakistani population was not good according to our study.

Assessing Public Opinion Regarding COVID-19 Vaccinations in Pakistan: Knowledge, and Perceptions of General Public

The COVID-19 infodemic can be counteracted by clear and consistent communication of scientific evidence and improved health literacy between the public and informants. For complete eradication of COVID-19, several vaccines are approved in various countries for public use by regulatory authorities. Assessing public perception regarding COVID-19 vaccination is an important area of research. In the current study, we aim to evaluate the opinions of individuals from multiple localities about COVID-19 and its vaccination through an online survey. Participants of the study were divided into different groups based on age, profession, demography, and income, and their opinions were calculated in percentage. In age group analysis we reported the highest willingness, 62.8 % (n=22) in age group 30-40, followed by 60 % (n=3) in age group >50, 58.6 % (n=244) in age group 20-30, 57.95 % (n=51) was in age group 15-20 and the least willingness, 33.33 % (n=4) in age group 40-50. The highest disagreement regarding vaccination of 60 % was found in age group >50, followed by 33.3 % in the age group 40-50, 14.7 % in the age group 20-30, 11.4 % in the age group 15-20 and 30-40. Similarly based on profession, maximum acceptability, 59.1 % (n=262) was reported in students, followed by a businessman (68.7 %, n=11), professional workers (3.5 %, n=20). Likewise, in demographic analysis, individuals from Khyber Pakhtunkhwa (KP) (61.3 %, n=200) were found more enthusiastic for vaccination, followed by AJK (58.33 %, n=7) and Islamabad (58.1 %, n=32). In the same way, people with income range $435-$621/month showed the highest willingness (65.7 %, n=69) regarding vaccination, followed by income group ($621 or more $s/month). Surprisingly, individuals from the low-income group were found more interested in vaccination as compared to the higher-income group. Comparatively low interest of high-income group individuals may be due to more exposure to conspiracy theories shared on social media. © Pakistan Academy of Sciences.

Covid-19 pandemic: Psychological impact on postgraduate gynae residents in pakistan

Objective: The aim of this study is to determine the psychological impact (anxiety, stress and depression) on postgraduate Gynae residents in Pakistan during COVID-19. Study Design: Cross-sectional study Place and Duration: The study was conducted through a questionnaire of Google Proforma which was distributed among the PGRs of Gynae and Obs department of different centres of Pakistan. The study was conducted for nine months during from April 2020 to December 2020. Methods: Total 180 participants (PGRs) were presented in this study. Complete characteristics of the participant were obtained. Postgraduate Gynae Residents from different centers were enrolled in this study. DASS-21 scale was used to measure the severity of anxiety, depression and stress among all participants. Complete data was analyzed by SPSS 24.0 version. Results: Mean age of the participants was 30.24±3.08 years. 109 (60.5%) participants were married and the rest 71 (39.5%) were unmarried residents. Frequency of depression was found among 130 (72.2%) participants followed by anxiety 118 (65.5%), stress found in 105 (58.3%) participants. Conclusion: We concluded in this study that the prevalence of psychological impacts on Gynae residents were significantly higher in terms of mild, moderate and severe intensity. Early detection and prevention of factors i.e. depression, anxiety and stress are necessary in hospitals.

Timing of endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute gallstone pancreatitis during the first wave of COVID-19 pandemic, are we following the guidelines!

Aims: Introduction Gallstone is well known, among other aetiologies, cause of Acute pancreatitis . It is crucial to makeearly diagnosis as different treatment approached is recommended which includes early ERCP and cholecystectomy . In aproven or suspected gallstone pancreatitis, patients should undergo a therapeutic ERCP within 72 hours as per BSGguidleines . Methods We retrospectively studied all ERCP procedures done during the first wave of Covid-19 between Jan-Jun 2020.Data were retrieved using electronic patient records as well as endoscopic reporting applications. Results 113 ERCP had been performed in our hospital during the first wave of Covid-19. Among them, they was only 8patients who had ERCP for Acute Gallstone Pancreatitis. 5 patients only had ERCP during the 72 hours of the onset of painoccurred in 60 % (n = 3). 2 patients did not have their ERCP within the recommended time and one patient received medicaltreatment. Conclusions 60 % adherence is not adequate. We recommend development of local stander of procedure, pathway, orenhancement of early referral to Endoscopy unit. We recommend that all referral to ERCP will need to be reviewed withmore urgency. Feedback to the acute medical team and emergency department to make more urgent referral tohepatobiliary team when gallstone pancreatitis is suspected.

Assessment of anxiety level among doctors and paramedical staff in a tertiary care hospital, during covid-19 pandemic

Objective: To assess the level of anxiety among doctors and paramedical staff working in a tertiary care Hospital during COVID-19-Pandemic. Study Design: Cross-sectional study Place and Duration of Study: This study was conducted at the Abwa Hospital & Research Centre attached with Abwa Medical College, Faisalabad for the period of three months i.e. May, 2020 to July, 2020. Materials and Methods: Total 55 participants including 11 doctors & 44 paramedics serving specifically COVID-19 patients were selected to assess the level of anxiety and its associated factors. Results: Out of total 55 participants, the level of anxiety was higher among medical doctors (mean score =6.91+7.0) as compared to paramedical staff (mean score3.25+4.68) where 31.7% of frontline health workers reported anxiety on BAI. 20 % (n=11) mild symptoms, a single worker only reported moderate anxiety 7.2% reported severe anxiety. Conclusion: During the pandemic of COVID-19 disease, among health care workers of ABWA hospital, medical doctors reported anxiety problems to a greater extent as compared to paramedical staff although intensity of anxiety was disproportionately higher in paramedical group. Considering this, there is a need of implementing programs of mental health being for health care professionals as an essential component of every epidemic at both national and international level.

Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders.

COVID-19 is a global pandemic, thus requiring multiple strategies to develop modalities against it. Herein, we designed multiple bioactive small molecules that target a functional structure within the SARS-CoV-2's RNA genome, the causative agent of COVID-19. An analysis to characterize the structure of the RNA genome provided a revised model of the SARS-CoV-2 frameshifting element, in particular its attenuator hairpin. By studying an RNA-focused small molecule collection, we identified a drug-like small molecule (C5) that avidly binds to the revised attenuator hairpin structure with a K d of 11 nM. The compound stabilizes the hairpin's folded state and impairs frameshifting in cells. The ligand was further elaborated into a ribonuclease targeting chimera (RIBOTAC) to recruit a cellular ribonuclease to destroy the viral genome (C5-RIBOTAC) and into a covalent molecule (C5-Chem-CLIP) that validated direct target engagement and demonstrated its specificity for the viral RNA, as compared to highly expressed host mRNAs. The RIBOTAC lead optimization strategy improved the bioactivity of the compound at least 10-fold. Collectively, these studies demonstrate that the SARS-CoV-2 RNA genome should be considered druggable.