Meeting the service needs of youth with and without a self-reported mental health diagnosis during COVID-19

Background: The COVID-19 pandemic catalyzed major changes in how youth mental health (MH) services are delivered. Understanding youth's MH, awareness and use of services since the pandemic, and differences between youth with and without a MH diagnosis, can help us optimize MH services during the pandemic and beyond. Objective(s): We investigated youth's MH and service use one year into the pandemic and explored differences between those with and without a self-reported MH diagnosis. Method(s): In February 2021, we administered a web-based survey to youth, 12-25 years, in Ontario. Data from 1373 out of 1497 (91.72%) participants were analyzed. We assessed differences in MH and service use between those with (N=623, 45.38%) and without (N=750, 54.62%) a self-reported MH diagnosis. Logistic regressions were used to explore MH diagnosis as a predictor of service use while controlling for confounders. Result(s): 86.73% of participants reported worse MH since COVID-19, with no between-group differences. Participants with a MH diagnosis had higher rates of MH problems, service awareness and use, compared to those without a diagnosis. MH diagnosis was the strongest predictor of service use. Gender and affordability of basic needs also independently predicted use of distinct services. Conclusion(s): Various services are required to mitigate the negative effects of the pandemic on youth MH and meet their service needs. Whether youth have a MH diagnosis may be important to understanding what services they are aware of and use. Sustaining pandemic-related service changes require increasing youth's awareness of digital interventions and overcoming other barriers to care.Copyright © 2023, Canadian Academy of Child and Adolescent Psychiatry. All rights reserved.

Molecular docking, Molecular dynamics, and AD-MET investigation of selected phytochemicals as promising inhibitors of SARS-CoV-19 targets

There are a few small organic molecules against SARS-CoV-2 that has been discovered since the epidemic commenced in November 2019. The con-ventional medication discovery approach demands more than a decade of the year of laborious research and development and substantial financial commitment, which is not achievable in the face of the current epidemic. This study aims to discover and recognize the most effective and promising molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 120 phytochemicals from six different Ayurveda medicinal plants. The binding affinities were studied using a structure-based drug design of molecular docking, divulging 10 molecules possessing greater affinity towards the target than the reference drug molnupiravir. Molecular docking analysis identified 10 phytochemicals, castalagin, wedelolactone, arjungenin, bet-ulin, galbacin, shinpterocarpin, liquiritin, cordioside, licopyranocoumarin, and daucosterol from different kinds of ayurvedic medicinal plants phyto-chemicals possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely castalagin and wedelolactone, with low binding energies, were the most promising. Furthermore, we carried out MD simulations for the castalagin-protein complexes based on the docking score. Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike the protein of SARS-CoV-2. © 2023, Zita Medical Managent. All rights reserved.

An in silico investigation to identify promising inhibitors for SARS-CoV-2 Mpro target.

BACKGROUND: A limited number of small molecules against SARS-CoV-2 has been discovered since the epidemic commenced in November 2019. The conventional medicinal chemistry approach demands more than a decade of the year of laborious research and development and a substantial financial commitment, which is not achievable in the face of the current epidemic. OBJECTIVE: This study aims to discover and recognize the most effective and promising small molecules by interacting SARS-CoV-2 Mpro target through computational screening of 39 phytochemicals from five different Ayurveda medicinal plants. METHODS: The phytochemicals were downloaded from PubChem, and the SARS-CoV-2 protein (PDB ID: 6LU7; Mpro) was taken from the PDB. The molecular interactions, binding energy, and ADMET properties were analyzed. RESULTS: The binding affinities were studied using a structure-based drug design of molecular docking, divulging 21 molecules possessing greater to equal affinity towards the target than the reference standard. Molecular docking analysis identified 13 phytochemicals, sennoside-B (-9.5 kcal/mol), isotrilobine (-9.4 kcal/mol), trilobine (-9.0 kcal/mol), serratagenic acid (-8.1 kcal/mol), fistulin (-8.0 kcal/mol), friedelin (-7.9 kcal/mol), oleanolic acid (-7.9 kcal/mol), uncinatone (-7.8 kcal/mol), 3,4-di-O-caffeoylquinic acid (-7.4 kcal/mol), clemaphenol A (-7.3 kcal/mol), pectolinarigenin (-7.2 kcal/mol), leucocyanidin (-7.2 kcal/mol), and 28-acetyl botulin (-7.2 kcal/mol) from Ayurvedic medicinal plants phytochemicals possess greater affinity than (-7.0 kcal/mol) against SARS-CoV-2-Mpro. CONCLUSION: Two molecules, namely sennoside-B, and isotrilobine with low binding energies, were the most promising. Furthermore, we carried out molecular dynamics simulations for the sennoside-B protein complexes based on the docking score. ADMET properties prediction confirmed that the selected docked phytochemicals were optimal. These compounds can be investigated further and utilized as a parent core molecule to create novel lead molecules for preventing COVID-19.

Computational search for potential COVID-19 drugs from ayurvedic medicinal plants to identify potential inhibitors against SARS-CoV-2 targets.

BACKGROUND: To date, very few small drug molecules are used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been discovered since the epidemic commenced in November 2019. SARS-CoV-2 RdRp and spike protein are essential targets for drug development amidst whole variants of coronaviruses. OBJECTIVE: This study aims to discover and recognize the most effective and promising small molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 39 phytochemicals from five different Ayurveda medicinal plants. METHODS: The phytochemicals were downloaded from PubChem, and SARS-CoV-2 RdRp and spike protein were taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed. RESULTS: Molecular docking analysis identified some phytochemicals, oleanolic acid, friedelin, serratagenic acid, uncinatone, clemaphnol A, sennosides B, trilobine and isotrilobine from ayurvedic medicinal plants possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely oleanolic acid and sennosides B, with low binding energies, were the most promising. Furthermore, based on the docking score, we carried out MD simulations for the oleanolic acid and sennosides B-protein complexes. CONCLUSION: Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike protein of SARS-CoV-2.

IDENTIFICATION OF PROMISING PHYTOCHEMICAL INHIBITORS FOR SARS- CoV-2 FROM ROSA CENTIFOLIA BY INSILICO DOCKING STUDIES

Since November 2019, no cost-effective and potential small drug molecule has been discovered against the SARS-CoV-2 pandemic. The major disadvantage of conventional synthesis is the laborious research time for discovery and development with a huge economy that is not easily met by current pandemic conditions. The main aim of this study is to discover and identify the most effective and promising molecules against the three targets of SARS-CoV-2, such as protease, spike protein and RdRp, via molecular docking screening of various phytochemicals from Rosa Centifolia. The binding affinities were studied using a structure-based drug design of molecular docking. The study results showed that most constituents possess good affinity towards the target than standard drug N3 inhibitor. Among 27 compounds, multiflorin B showed the highest binding energies of -6.975, and -5.471 kcal/mol against protease and RdRp targets, respectively. The compound sabinene showed good interaction with spike protein with a docking score of -4.449 kcal/mol. Molecular ADMET profile estimation showed that the docked phytochemicals are safe. The present study indicates that the various active phytochemical constituents of Rosa Centifolia could inhibit SARS-CoV-2. © 2022 Deuton-X Ltd. All rights reserved.

Role of Baricitinib in moderate to severe COVID-19, a case control study from a South Indian tertiary care setting (preprint)

Background Baricitinib is a Janus kinase inhibitor with known anti-inflammatory effects and has been explored for beneficial outcomes in COVID-19 therapeutic management however with paucity of data on its effects on secondary infections and thrombosis. We aimed to assess the efficacy and all-cause mortality among moderate to severe COVID − 19 on a retrospective cohort of patients who received adjunct baricitinib as compared to a matched cohort who received standard of care for moderate to severe Covid 19.Methods The retrospective case control study conducted at 1300-bedded South Indian tertiary care centre from April to October 2021 recruited moderate to severe Covid patients receiving baricitinib therapy for at-least 72 hours into case group. Age and severity matched Covid patients who received standard of care without baricitinib were enrolled as control arm in 1:1 ratio. Data of the study groups on baseline characteristics, medications including antivirals, steroids, antibiotics and outcome measures were obtained. Study outcomes included all-cause mortality, daily clinical improvement assessed by ≥ 1-point improvement in WHO Ordinal Scale scores, multi-organ dysfunction syndrome, incidence of thrombotic events and secondary infections.Results Among the 527 moderate to severe COVID 19 patients in the study period, 75 patients each were recruited into case and control groups respectively. Mean age of case and control groups were 60.82 ± 13.03 and 61 ± 13.48 years respectively. 28-day mortality rate was 33.3%(n = 25) in the case group and 48%(n = 36) in the control group (p = 0.24, RR = 0.79, CI 95%). An absolute risk reduction of 16.75% was observed (NNT = 6) between the groups. All-cause mortality was 42.7%(n = 64) with 27(n = 36%) and 37(n = 49.3%) deaths in the case and control groups respectively(p = 0.09). Kaplan-Meier survival analysis revealed survival distributions to be significantly different between case and control groups (Log rank: p = 0.048). Clinical improvement assessed by decrease in WOS ≥ 1 was demonstrated to be higher in cases (n = 35,47%) than controls (n = 28,37.7%)(p = 0.32).Conclusion Our retrospective case control study revealed lower mortality and higher proportion of patients attaining clinical improvement as measured by at least one-point improvement of WHO ordinal scale in patients admitted with moderate to severe Covid 19, which did not attain statistical significance.

Discovery of Immunomodulators from Plant Kingdom Targeting IL-6 for the Effective Management Therapy of SARS-CoV-2

The present study was conducted because of the recent scenario of this pandemic coronavirus outbreak worldwide. Currently, this disease cannot be treated through specific vaccines and therapeutic medicines. While many vaccines are being investigated, it would take some time for these to be accessible to the masses. Eventual evidence indicates that many COVID-19 patients may die from an irregular release of cytokines called as Cytokine Release Syndrome (CRS) due to the excessive reaction of their immune systems. In worsening patients with COVID-19, CRS played a significant role, from pneumonia via ARDS to cumulative systemic inflammation and eventually to a failing of the multi-system organ. In COVID-19 individuals, a large number of cytokines, including IL-6, IL-1, IL-2, IL-10, TNF-α, and IFN-α, participate in the ‘cytokine storm,’ but IL-6, whose higher serum levels are associated with respiratory failure, ARDS, and adverse clinical outcomes, tends to be a critical factor. In China, the COVID-19 mortality indicator has been tested by a multi-centre retrospective analysis in 150 COVID-19 patients. The study analysed that 82 cases are resolved from COVID-19 and 68 cases are dead due to enhancement of IL-6 levels in the serum. In this research, the secondary plant metabolites from Indian traditional medicine are identified through a computational technique and the selected seedling metabolite is sealed to block the IL-6 receptor. © 2022, Informatics Publishing Limited. All rights reserved.

Identification of (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate as multiple inhibitors of SARS-CoV-2 targets;a systematic molecular modelling approach† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra01603b

Coronavirus disease of 2019 (COVID-19) is a zoonotic disease caused by a new severe acute respiratory syndrome (SARS-CoV-2) which has quickly resulted in a pandemic. Recent anti-COVID-19 drug discoveries are leaning towards repurposing phytochemicals which have been previously reported for SARS and MERS-CoV outbreaks. However, they have been either virtually screened or tested so far against mono targets and the potent derivatives of virtually sorted lead molecules remain elusive. We aimed to identify the phytochemicals having potentials to inhibit SARS CoV-2 infection via multiple targets. The selected 132 phytochemicals were virtually screened using a structure based in silico technique against main protease (Mpro) which is a potential target of SARS CoV-2. Six compounds were selected based on the LibDock scores and further subjected to induced fit docking using the CDOCKER module of DS. Two compounds namely cinnamtannin-B and gallocatechin gallate were identified as top HITS against main protease (Mpro). Based on the Lipinski rule of five (L-ROF) and synthetic feasibility, gallocatechin gallate was taken for our further studies. Six analogues of gallocatechin gallate were screened against the next important targets such as RNA-dependent RNA polymerase (RdRp), angiotensin converting enzyme-2 (ACE2), transmembrane protease serine -2 (TMPRSS2) and interleukin-6 (IL-6) along with main protease (Mpro). Our molecular docking results reveal that a gallocatechin analogue (GC-2) namely (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate has shown potential to inhibit multiple targets of SARS CoV-2. Further, the molecular dynamics study was carried out to ascertain the stability of the GC-2 and RdRp complex. Structure-based insilico-guided screening of potential polytargeting anti-COVID phytochemical: gallocatechin gallate analogue.

An atypical occurrence: Liver pathology related to the COVID-19 vaccination

Introduction: This case highlights an atypical hepatic pathology after the COVID 19 vaccine and is an important contribution to the literature given the newness of the vaccine. Case Description/Methods: A 34-year-old male with no significant past medical history presented after his first COVID 19 vaccine with headaches, fevers up to 39C and myalgias 5 days after his vaccine. No recent travel or drugs. Labs revealed Hb 10.8, T-bilirubin peaked to 4.6, admitted with T bilirubin 3.7, D bilirubin 2.5, AST 364, ALT 377, ALP 230, V lac 1.3, Chronic liver work up A1AT, Ceruloplasmin, IgG, ANA, AMA, EBV, CMV IgM unremarkable, only ASMA mildly positive 1:20. Antibiotics were initiated and blood, urine cultures, HIV, respiratory panel, Covid, hepatitis panel were negative. HIDA, US and CT abdomen showed normal spleen and liver size. For headaches, CT and MRI brain were unremarkable. Peripheral blood leukemia-lymphoma panel showed an inversion of CD4/CD8 ratio, a nonspecific finding in viral and reactive processes. Liver biopsy showed atypical CD8-positive T cell population identified in sinusoids (focal clustering, irregular membrane contour). Findings of undetermined significance and can be related to drug were determined to be related to his recent COVID 19 vaccination. Discussion: His differentials included viral etiology or autoimmune liver disease due to activation of immune system from COVID-19 vaccine;labs and biopsy pointed toward liver pathology related to vaccination.