ABSTRACT
Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the biosynthesis of pyrimidine, which catalyzes the oxidation of dihydroorotate to orotate. Uridine monophosphate is biosynthesized by orotate. DHODH inhibitors have been shown to have antiviral activity against cytomegalovirus, Ebola, influenza, Epstein-Barr virus, and picornavirus. The anti-SARS-CoV-2 activity of DHODH inhibitors has also been investigated. DHODH inhibitors, including leflunomide and its metabolite teriflunomide, have been found to have anti-SARSCoV-2 activity. In relation to the importance of this enzyme (i.e., DHODH) in drug design, the present study aimed to develop statistically robust and interpretable 2D and 3D-quantitative structure-activity relationship (QSAR) models based on a dataset of 92 molecules of biologically active 2-aryl-4-quinoline carboxylic acid analogs, reported as DHODH inhibitors. The correlation coefficient (R2) values of the training set of the partial least squares (PLS) and all five Kernel-based PLS models for the respective fingerprints were found to be 0.7091, 0.8336 (linear), 0.7586 (radial), 0.8606 (dendritic), 0.6832 (desc), and 0.7670 (Molprint 2D), respectively (R2 ≈ 0.9). However, the external validation coefficient (Q2) values of the test set were found to be 0.7009, 0.7503 (linear), 0.7737 (radial), 0.8250 (dendritic), 0.6756 (desc), and 0.7533 (Molprint 2D), respectively (Q2 > 0.6). The developed 4-point pharmacophore model (ARRR_1), with one hydrogen bond acceptor and three aromatic rings, was found to be crucial in preserving the activity of 2-aryl-4-quinoline carboxylic acid analogs as DHODH inhibitors. Furthermore, the molecular docking of DHODH inhibitors against SARS-CoV-2 target proteins revealed the significant role of DHODH inhibitors. © 2023, Physical Chemistry Research. All Rights Reserved.
ABSTRACT
Purpose : Amidst the COVID-19 pandemic, telemedicine has emerged as a safe and cost-effective alternative to traditional, in-person ophthalmology clinic visits. To better understand the implications of this technology on the patient-physician relationship, this study assessed patient perspectives about telemedicine to identify areas for improvement. Methods : A cross-sectional survey was distributed to patients at University Retina during July 2021. Responses regarding telehealth's ability to ease anxiety of contracting COVID-19, efficiency, patient education, quality of examination, and convenience were collected on a 5-point Likert scale. A positive attitude was defined as ≥ 4 average Likert rating for all questions. Frequencies of positive attitudes were compared across demographic factors by the Pearson chi-square test. Multivariate analysis was used to evaluate factors influencing patient preference for telehealth over traditional visits. Results : Of 103 respondents, most were female (53.8%), aged 65-74 (34.6%), and high school educated (46.2%). 38% of patients did not know their diagnosis and 62.1% had no prior history of telehealth usage. Overall, patients had a neutral attitude towards telehealth (mean Likert rating (SD) = 3.11/5 ± 0.82). Nearly one-third (31%) preferred telehealth over face-to-face visits. Questions regarding “patient education” had the greatest proportion of positive attitude, whereas “efficiency” had a largely negative attitude (both 63.1%). “Convenience” of telehealth yielded the highest number of responses in strong agreement or disagreement (38.9%). Patients with no history of telehealth usage more frequently reported negative attitudes compared to those with prior experience (87.5% vs. 71.8%, p = 0.046). Patients tended to respond more positively as education level increased, but this trend was not statistically significant (p = 0.18). On multivariate analysis, patients younger than 75 were more likely to prefer telehealth over in-person visits compared to patients 75 or older (odds ratio [OR] = 2.25, p = .007). Patient gender, knowledge of diagnosis, and history of past telehealth usage did not predict preference for telemedicine. Conclusions : Patients responded with a net neutral outlook on telehealth, indicating room for improvement. Efforts should focus on addressing technological inefficiencies and age-related barriers to patient satisfaction.
ABSTRACT
Objective: To study SARS-CoV-2 viral load in maternal and neonatal bodily fluids, Passage of anti-SARS-CoV-2 antibody through placenta and breastmilk, and incidence of fetoplacental infection. Methods: The data were gathered from five databases and included a review of research articles published between 2020 and 2021. PubMed Google Scholar The following terms were used in the search: 1. Clinical symptoms of the mother, 2. The ratio of negative to positive RT-PCR test results in infants, 3. Ratios of normal to aberrant IgG and IgM, 4. Antibody Placental Transfer, 5. Time period for maternal immunization to produce effective antibodies, 6. Neonatal Immune Response, 7. Antibodies are transferred through breast milk after moms have been immunised. Results: Several prospective and retrospective studies conducted in Wuhan, Philadelphia, Florida and Massachusetts consisted of seropositive as well as seronegative pregnant women. SARS-CoV-2 antibodies were detected in the sera of the mother and correlated with the antibodies detected in the neonatal blood. Significant transfer of IgG SARS-CoV-2 antibodies through placenta and breast milk was observed;that is, positive correlation was found between SARS-CoV-2 IgG concentrations in cord and maternal sera (= 0.886;< .001). Not only passively, but mothers infected during the peripartum period protect the newborn by actively stimulating and training the neonate system via breastmilk immune complexes. Conclusion: We here highlight novel insights arising from recent research endeavours on the transmission of SARS-CoV-2 antibodies from a mother to an infant.