2C5-surface modified nanocarriers targeting neutrophil extracellular traps

Background: Neutrophil extracellular traps (NETs) are composed of processed chromatin bound to granular and selected cytoplasmic proteins and released by neutrophils. NETs consist of smooth filaments composed of stacked nucleosomes. Fully hydrated NETs have a cloud-like appearance and occupy a space 10-15-fold larger than the volume of the cells they originate from. DNases are the enzymes that cleave extracellular DNA including NETs. Together with their protective role in microbial infections, NETs are involved in multiple pathological processes and represent key events in a variety of pathologies including cancer, autoimmunity, and cardiovascular disease. Sites of NETs concentration are dangerous for the host if the process of NETs formation becomes chronic or the mechanism of NETs removal does not work. NETosis has been linked to the development of periodontitis, cystic fibrosis, type 2 diabetes, COVID-19 or rheumatoid arthritis as well as cancer progression. Purpose(s): Thus, the destruction of NETs is of primary significance in many pathologies. In our approach, we are focusing on mimicking one of the natural mechanisms of destroying excessive NETs by delivering deoxyribonuclease I to the specific site of pathological NETs accumulation by modifying the nanoparticles using an anti-nucleosome monoclonal antibody (2C5). The antibody is specific to nucleosomes and can recognize histones in NETs. DNase I is U.S. Food and Drug Administration (FDA)-approved active component and is commonly used in therapeutic methods of modern medicine for cystic fibrosis to clear extracellular DNA fibers in the lungs and systemic lupus erythematosus. Recent findings have also shown the effectiveness of DNase I in the digestion of NETs. However, the low serum stability and fast deactivation by environmental stimuli have been considered as the limiting factors for clinical applications of DNase I, which can be overcome by its targeted specific delivery in pharmaceutical nanocarriers. Method(s): In this study, we generate NETs in vitro using human neutrophils and HL-60 cells differentiated into granulocyte-like cells. We used interleukin-8, lipopolysaccharide from E.Coli (LPS), phorbol myristate acetate (PMA), and calcium ionophore A23187 (CI) to generate the NETs. We confirmed the specificity of 2C5 toward NETs by ELISA, which showed that it binds to NETs with the specificity like that for purified nucleohistone substrate. We further utilized that feature to create two delivery systems (liposomes and micelles) for DNAse I enzyme to destroy NETs, which was confirmed by staining NETs with SYTOX Green dye and followed by flow cytometric measurements and microscopic images. Conclusion(s): Our results suggest that 2C5 could be used to identify and visualize NETs and serve as a ligand for NET-targeted diagnostics and therapies. Also, we proved that our carrier can successfully deliver DNase to NETs to provide their degradation.

Plasma expansion and renal perfusion in critical COVID-19 with AKI

Introduction: We have previously described decreased renal perfusion in acute kidney injury (AKI) due to critical COVID-19 [1]. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in patients with AKI compared to similar patients without AKI. Method(s): A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5 ml/kg Ringer's Acetate (Baxter). Mean arterial pressure (MAP) was recorded before plasma infusion and compared with maximum value after. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects. Result(s): Nine patients with AKI and eight without were included in the study. Patients in both groups were of similar mean age and weight, 66 (SD 8) years and 94 (SD 22) kg in AKI group and 64 (SD 15) years and 93 (SD 20) kg in patients without AKI. The response to plasma expansion was similar with increased MAP by 18 (CI 8-28) mmHg and 20 (CI 10-31) mmHg respectively (Table 1). Total renal perfusion and cortical perfusion was not significantly changed by plasma expansion, however there was a reduction of medullary perfusion in patients without AKI (Table 1). Conclusion(s): Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with ARDS due to COVID-19.

AUTOPHAGY AND Acyl-CoA-BINDING PROTEIN INFLUENCE COVID-19 SEVERITY

Background: Autophagy, a cytosolic-structure degradation pathway, allows production of IL21 by CD4 T-cells and efficient cytolytic responses by CD8 T-cells. Autophagy is in part regulated by acyl-CoA-binding protein (ACBP) which has two functions. Intracellular ACBP favors autophagy, whereas secreted extracellular ACBP inhibits autophagy. Herein, we assessed whether autophagy and the ACBP pathway were associated with COVID-19 severity. Method(s): Through the BQC-19 Quebec biobank, somalogic proteomic analysis was performed on 5200 proteins in plasma samples collected between March 2020 and December 2021. Plasma from 903 patients (all data available) during the acute phase of COVID-19 were assessed. COVID-19 severity was stratified using WHO criteria. In vitro, ACBP intracellular levels, autophagy levels (LC3II) and IL21 production were assessed by flow in PBMCs after a 24h stimulation with IL6, phorbol myristate acetate (PMA)+ionomycin or lipopolysaccharide (LPS). Plasma levels of anti-SARS-CoV-2 (full spike protein or RBD) IgG were assessed by ELISA. Result(s): Median age of the cohort was 62 yo, 48% were female, 55% had comorbidities (see table). Increasing plasma levels of ACBP were found with severity (mild, moderate, severe and fatal groups having 5.3, 7.3, 9.5 and 10.6 RFU/50muL of plasma, respectively, p< 0.001 for all comparisons). Patients with comorbidities had higher plasma ACBP levels (7.4 vs 6.4 RFU/50muL, p< 0.001). Plasma ACBP levels were higher during the delta and omicron-variant periods (8.4 vs 6.8 RFU/50muL;p< 0.001). Plasma ACBP levels correlated with LC3II levels (r=0.51, P< 0.001) and IL6 (r=0.41, p< 0.001), but neither with markers IL1beta nor IL8. ACBP levels negatively correlated with IL21 levels (r=-0.27, p< 0.001), independently of age, sex, and severity. ACBP levels were not associated with levels of anti-SARS-CoV-2 IgG levels. In vitro, IL6 stimulation of healthy control PBMC induced extracellular ACBP release. Moreover, adding recombinant ACBP: 1) reduced autophagy in lymphocytes and monocytes upon polyclonal stimulation with PMA/ionomycin or LPS;2) reduced intracellular production of IL21 in T-cells after PMA/ ionomycin stimulation. Conclusion(s): Plasma ACBP levels were inversely linked with IL21 levels, suggesting that autophagy and IL21 allow control of SARS-CoV-2 infection, independently of the level of SARS-CoV-2 antibody secretion. ACBP is a targetable autophagy checkpoint and its extracellular inhibition may improve SARS-CoV-2 immune control. (Table Presented).

ZINC ADJUVANT TREATMENT IN SARS-CoV-2: A RANDOMIZED CLINICAL TRIAL

Background: The immune system is highly susceptible to changes of zinc levels and this might imply a different response against infection. Prior evidence suggests some benefit on viral infection prognosis after zinc supplementation. We aim to study the efficacy of zinc supplementation in SARS-CoV-2 infection outcomes. Method(s): This is an unicenter prospective, randomized cliinical trial where unvaccinated individuals with moderate SARS-CoV-2 infection without endorgan failure were randomized to standard of care+oral zinc for 15 days (three times per day a tablet of 83mg of Zn acetate equals to 75 mg of Zn element) (zSoC) (n =37) or standard of care alone (SoC) (n = 34). The primary combined outcome was death due to SARS-CoV-2 or intensive care unit (ICU) admission. Secondary outcomes included length of hospital stay (LoS) and time to clinical stability (defined as: oxygen saturation >94% [FiO2 21%], normalized level of consciousness [baseline], HR < 100rpm, systolic BP >90mm Hg,Temperature < 37.2degreeC). Wilcoxon-Mann-Whitney test generalized Odds ratio (ORs) and 95% confidence intervals (CIs) for differences in outcomes between SoC and zSoC. A logistic regression model was fitted adjusted by age, sex, severity and comorbidity to compare the primary outcome between SoC and zSoC. Result(s): Seventy-one participants were recruited. No significant differences in terms of age, gender and comorbidities nor in SoC were found between groups (Table 1). 14-day Mortality was 2.90 % (2 participants) in the SoC group and none in zSoC. ICU admission rates were, respectively, 8 (23%) and 1 (2.7%) (OR: .098;95% CI .013-.766). The principal combined outcome occurred in 8 participants (23%) in SoC and in 2 (5.4%) in zSoC (OR: 0.18;95% CI .03-.946). In a logistic regression model adjusting by age, sex, comorbidity and severity the OR for the combined outcome in those in zSoC was 0.091 (95% CI: 0.007-0.913;p=0.045). LoS was shorter in zSoC (6.9 days (SD 6.1) vs 12.7 (SD 11.6);p=0.013) respectively. Time to clinical stability was significantly shorter in zSoC (5 days (SD 6.1)) compared to SoC (11.9(SD 9.1));p=0.005. No significant differences in changes in inflammatory markers were found among groups. No severe adverse events were observed during the study. Conclusion(s): Daily zinc supplementation with 240 mg of zinc acetate for 14 days during the acute phase of SARS-CoV-2 infection resulted in lower rates of severity (less death and ICU admission) and faster clinical recovery along with shorter hospital stay.

Polyethylenglycol and polysorbate evaluation for COVID vaccines in two patients with multiple drug allergies

Background: Covid 19 is a global epidemic. One of the most important steps in the fight against this epidemic is vaccination. mRNA vaccines are used in vaccination in our country. Among the additives in the vaccine, the substance with the highest allergenic risk is polyethylene glucose (PEG). There are different molecular weights of PEG. Another additive that has a high risk of cross-reaction with PEG as an additive is POLISORBAT 80. Skin tests with drugs containing PEG and POLISORBAT 80 and, if available, tests with vaccines are instructive. Among the drugs containing PEG: Moxifloxacin tablet, ciprofloxacin tablet, Amoxicillin clavulanic acid tablet;Medicines containing polysorbate include: Omalizumab vaccine, Mepolizumab vaccine. The results of the skin test with PEG-containing methylprednisolone (DEPO-MEDROL) and POLYSORBAT-containing triamcinolone (KENACORT-A) in order to be evaluated in terms of vaccine in our 2 patients who had multiple drug sensitivities before were shared. Method(s): Case 1: 33 y, F *There are diagnoses of urticaria and angioedema. Urticaria 30 minutes after taking aspirin, levofloxacin, cefdinir tablet;5 minutes after taking ciprofloxacin tablets, he has anaphylaxis. *Applies before Biontec vaccine. *The patient had a history of anaphylaxis with PEG-containing ciprofloxacin. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *The patient for whom Biontec vaccine was not recommended received Synovac vaccine without any problems. Case 2: 52 years, F * He has a diagnosis of urticaria. 5 minutes after general anesthesia and local anesthesia;The patient who had cardiac arrest 3 times was evaluated. The patient, who had Synovac for 2 times without any problems, wanted to have the 3rd dose of Biontec vaccine. *Tested with general -local anesthetic agents. *Ciprofloxacin skin tests are negative;Urticaria plaques developed after 30 minutes of 1/4 tb in oral provocation. In the skin tests performed with DEPO-MEDROL and KENACORT-A, 1/100 intradermal test was positive. *Biontec vaccine is not recommended. Result(s): A safer vaccination is ensured by testing with additives in Covid 19 vaccines. Conclusion(s): Drug additives should also be kept in mind in patients with multiple drug allergies.

Synthesis and crystal characteristics of nirmatrelvir

Several synthetic routes of nirmatrelvir (the ingredient of a new drug to treat COVID-19 made by Pfizer) have been reported. We focused on a second route to improve the synthetic method of nirmatrelvir with a methodology that included different steps. The first step was an analysis of reaction byproducts using acetonitrile as a solvent of the condensation reaction to improve the inversion rate. Then, we used isobutyl acetate as a crystalline solvent to obtain the key intermediate as a solvate, which was a stable crystal product with high purity. Complementarily, we also used trifluoroacetic anhydride as the primary-amide dehydrating agent, and 2-methyl tetrahydrofuran as the solvent to prepare nirmatrelvir, which led to an overall yield of 48% via four steps and a purity of 99.5% according to high-performance liquid chromatography. We also investigated the crystal form of nirmatrelvir: the single-crystal features and transformation from a crystal form to nirmatrelvir were dependent upon temperature. Our data have great value for study of the synthetic method and crystal stability of nirmatrelvir. © 2023 The Royal Society of Chemistry.

Symptoms compatible with hypersensitivity reactions after receipt of the first and second dose of COVID-19 vaccine

Background: Until January 2022, 8.975.458 cases of COVID-19 have been reported in Spain. In December of 2020, the European Union authorized the first mRNA vaccines against SARS-COV- 2, developed by Pfizer-BioNTech and Moderna, with two doses separated by 21 and 28 days, respectively. Reports of severe allergic reactions, including anaphylaxis, have prompted concern that the new mRNA vaccine platform has the potential to cause allergic reactions (including anaphylaxis) at a greater rate than other vaccines. Method(s): Immunization process started at Hospital Ramon y Cajal (Madrid, Spain) in January 2021. The hospital provided a form to report any adverse effect after the first or second dose of the vaccine. Until today, in our Allergy Department, we have received more than 500 patients with suspected adverse reaction to the vaccine, although the data in this publication are collected from January 2021 to September 2021. All of them were referred from different services (Occupational Risk Prevention Department, Preventive Medicine Department, General Practitioners and other specialties) by telephone, e-mail or personally at our service. Result(s): Out of the 139 vaccinated patients who reported adverse effects, 131 had a reaction with the first dose, of whom 65% were women. 51% were local reactions and 49% systemic, of which 62% were immediate reactions. We performed diagnostic tests in 55% of the patients: prick test (with macrogol, triamcinolone, dexketoprofen, methylprednisolone acetate, PEG), ID test (with triamcinolone, dexketoprofen, methylprednisolone acetate) with immediate reading and delayed reading in case of delayed reactions, epicutaneous tests (with PEG and polysorbate 80) and blood tests in systemic reactions. All diagnostic tests showed negative results. 82% of patients that reported adverse effects after the first dose tolerated the second dose of the vaccine without incidents. Only one patient had a reaction to the first and second dose despite a negative study, a 58-year- old woman who presented an urticarial rash 24 hours after administration. 8 patients, all of them women, were referred for reaction after the second dose, 87% of whom had tolerated the first dose. Conclusion(s): This single-center experience suggests that most patients who had mild reactions to the first dose of mRNA vaccines have received the second dose uneventfully or with only mild repeat reactions.

New Sesquiterpene Glycosides from the Flowers of Aster koraiensis and Their Inhibition Activities on EGF- and TPA-Induced Cell Transformation.

In total, four new eudesmane-type sesquiterpene glycosides, askoseosides A-D (1-4), and 18 known compounds (5-22) were isolated from the flowers of Aster koraiensis via chromatographic techniques. Chemical structures of the isolated compounds were identified by spectroscopic/spectrometric methods, including NMR and HRESIMS, and the absolute configuration of the new compounds (1 and 2) was performed by electronic circular dichroism (ECD) studies. Further, the anticancer activities of the isolated compounds (1-22) were evaluated using the epidermal growth factor (EGF)-induced as well as the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell transformation assay. Among the 22 compounds, compounds 4, 9, 11, 13-15, 17, 18, and 22 significantly inhibited both EGF- and TPA-induced colony growth. In particular, askoseoside D (4, EGF: 57.8%; TPA: 67.1%), apigenin (9, EGF: 88.6%; TPA: 80.2%), apigenin-7-O-ß-d-glucuronopyranoside (14, EGF: 79.2%; TPA: 70.7%), and 1-(3',4'-dihydroxycinnamoyl) cyclopentane-2,3-diol (22, EGF: 60.0%; TPA: 72.1%) showed higher potent activities.

Is The Co-administration of Metformin and Clomiphene Superior to Induce Ovulation in Infertile Patients with Poly Cystic Ovary Syndrome and Confirmed Insulin-resistance: A Double Blind Randomized Clinical Trial

Objective: This study aimed to compare the effects of clomiphene citrate (CC) combined with metformin or placebo on infertile patients with poly cystic ovary syndrome (PCOS) and insulin resistance (IR). Material(s) and Method(s): We included 151 infertile women with PCOS and IR in a university hospital from November 2015 to April 2022 in this prospective, double-blind, randomized, placebo-controlled trial. Patients were randomized into two groups;group A: received CC plus metformin (n = 76) and group B: received CC plus placebo (n = 75). The ovulation rate was the main outcome measure. Clinical pregnancy, ongoing pregnancy, live birth and abortion rates were secondary outcome measures. Result(s): There was no remarkable difference in ovulation rate in two groups. Moreover, no significant changes were observed in clinical pregnancy, ongoing pregnancy, live birth and abortion rates between two groups. A larger proportion of women in group A suffered from side effects of metformin (9.3% versus 1.4%;p=0.064), although this was not significant. Conclusion(s): In IR infertile women with PCOS, metformin pre-treatment did not increase the ovulation, clinical pregnancy and live birth rates in patients on clomiphene citrate.Copyright © 2023 Tehran University of Medical Sciences.

National Tele Mental Health Program (Tele MANAS) - An Initial Overview

Background (Dr Rahul Patley, Assistant Professor of Psychiatry- Goldman Sachs project, NIMHANS) The Government of India announced the National Tele Mental Health Programme (Tele MANAS) in the Union Budget in February 2022 to handle the aftermath of mental health issues arising out of the COVID-19 pandemic. It was launched on 10 Oct 2022 on World Mental Health Day as a 24X7 two-tier tele-mental health facility across India. Functioning of Tele Manas (Dr. Suchandra H H Assistant Professor of Psychiatry - Tele MANAS, NIMHANS & Dr C Naveen Kumar, Professor of Psychiatry, Principal Investigator of Tele MANAS, NIMHANS) A total of 51 Tele MANAS cells will be established across India to provide a broader range of mental health services (counselling, consultations, e-prescriptions, follow-ups, and linkages to in-person services) by various mental health specialists with five Regional Coordinating centres and 23 Mentoring Institutes. The NIMHANS function as the apex centre, NHSRC for resource mapping, and IIIT-B for technological support. Each Tele MANAS cell shall provide online services to callers through a trained counsellor and escalates to a mental health professional when needed. It also offers a linking service for inperson referrals to existing mental health resources. The curriculum of Tele MANAS (Dr Madhuri H Nanjundaswamy Assistant Professor of Psychiatry - Tele MANAS, NIMHANS & Dr Suresh Bada Math, Professor of Psychiatry, NIMHANS) The content of the curriculum includes components of training, manual preparation and accreditation courses for Tele MANAS Counsellors. The first edition of manuals were prepared and recently released by MoHFW. The training will be conducted in hybrid mode with both on-site and online components for Tele MANAS Counsellors. A selflearning module for counsellors is also planned. The concept of mental health in Tele MANAS (Dr Nileswar Das, Assistant Professor of Psychiatry- Goldman Sachs project, NIMHANS and Dr N Manjunatha, Additional Professor of Psychiatry, NIMHANS) Mental health in Tele MANAS is a spectrum concept that ranges from mental wellness to mental distress to mental illness. COVID-19 has increased mental distress exponentially compared to mental illness, emphasizing the need to focus on distress.

Attenuated effects of rivastigmine in induced cytokine storm in mice

Background: A cytokine storm is a serious clinical condition that complicates infectious diseases, for example, coronavirus disease 2019 (COVID-19), and non-infectious diseases such as autoimmune diseases and cancer and may often lead to death. The patients who are affected by the cytokine storm are almost always severe/critical and at risk for acute respiratory distress syndrome or eventually death. Pro-inflammatory cytokines such as interleukin 6 (IL-6), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) have been repeatedly shown to be related to the COVID-19 disease severity and mortality. In this study, our objective was to evaluate the attenuated effect of rivastigmine (RA) in a cytokine storm in Swiss Albino mice in which the cytokine storm was induced by lipopolysaccharide (LPS) and to explore their effects on IL-1 beta, IL-6, and TNF-alpha levels. Method(s): This study was carried with 60 male Swiss albino mice that were divided equally and randomly into six groups as follows: *Group AH: Apparently healthy control group which received no induction, not treated. *Group LPS: Induced using LPS at 5 mg/kg and no treatment administered. *Group DMSO: Induced and treated with 1% dimethyl sulfoxide (DMSO). *Group RA: Induced and treated with 0.5 mg/kg RA. *Group MPA: Induced and treated with 50 mg/kg methylprednisolone (MPA). *Group RMPA: Induced and treated with 0.25 mg/kg rivastigmine and 25 mg/kg of methylprednisolone. All the mice were treated with drugs or vehicles for three consecutive days before LPS induction. The mice were then injected with LPS intraperitoneally at a dosage of 5 mg/kg for systematic inflammatory stimulation. After 48 hours of LPS induction, all the mice were euthanized by light anesthesia with chloroform, and blood was collected for the quantitative determination of IL-1beta, IL-6, and TNF-alpha levels using the enzyme-linked immunosorbent assay (ELISA) technique. Result(s): Administration of LPS to Swiss albino mice caused a significant elevation of IL-1beta, IL-6, and TNF-alpha levels than in the healthy control group. Significant reduction of these parameters were observed in the RA and MPA groups when compared with those in the non-treated group. Conclusion(s): RA was found to be effective in attenuating the induced cytokine storm by suppressing IL-1beta, IL-6, and TNF-alpha levels, and the results with RA were comparable to that of MPA. A combination of half-doses of both RA and MPA administered together shows no obvious advantage when compared with that of each of them alone.Copyright © 2022 Mansoor, Raghif, licensee HBKU Press

Comparing the efficacy of meglumine acridon acetate and pentanedioic acid imidazolyl ethanamide in the outpatient treatment for ARVI during the COVID-19 pandemic.

This study compared the efficacy of different therapies for ARVI during the COVID-19 pandemic. Objective. To compare clinical efficacy of Cycloferon and Ingavirin in children aged 4-17 years treated in outpatient facilities during the epidemic season of SOVID-19. Patients and methods. This study included 101 patients who provided 143 oro-and nasopharyngeal swabs tested using certified PCR tests. Of them, 128 samples (89.5%) were positive, whereas 15 samples (10.5%) were negative. We identified the most common viruses circulating in January-May 2021, including (seasonal) coronaviruses (35.9%), rhinoviruses (20.3%), and other viruses. We also analyzed respiratory viruses that have circulated in Moscow during the last 6 years and found higher levels of seasonal coronaviruses. The most common ARVI symptoms in 2021 were fever, rhinitis, pharyngeal hyperemia, and fatigue. Fewer children had headache, cough, and enlarged lymph nodes. Results. We compared ARVI treatment with broad-spectrum antivirals in children aged between 4 and 17 years. Children in group 1 (n = 51) received Cycloferon, while children in Group (n = 50) received Ingavirin. Study participants were diagnosed with ARVI and moderate nasopharyngitis. Children from the Cycloferon group demonstrated a more significant dynamics of such clinical symptoms as headache (p < 0.05), cough (p < 0.01), rhinitis (p < 0.01), abundant mucus (p < 0.001), and enlarged lymph nodes (p < 0.001) than children from the Ingavirin group (there was a significant difference in the duration of these symptoms). Only 2 children from group 1 required antibiotics (3.4%), whereas in group 2, 11 children needed antibacterial therapy (22%).Copyright © 2022, Dynasty Publishing House. All rights reserved.

Antiviral Molecular Targets of Essential Oils against SARS-CoV-2: A Systematic Review

Essential oils are potential therapeutics for coronavirus disease 2019 (COVID-19), in which some of the volatile compounds of essential oils have been well known for their broad antiviral activities. These therapeutic candidates have been shown to regulate the excessive secretion of pro-inflammatory cytokines, which underlies the pathogenesis of severe COVID-19. We aimed to identify molecular targets of essential oils in disrupting the cell entry and replication of SARS-CoV-2, hence being active as antivirals. Literature searches were performed on PubMed, Scopus, Scillit, and CaPlus/SciFinder (7 December 2022) with a truncated title implying the anti-SARS-CoV-2 activity of essential oil. Data were collected from the eligible studies and described narratively. Quality appraisal was performed on the included studies. A total of eight studies were included in this review;four of which used enzyme inhibition assay, one—pseudo-SARS-CoV-2 culture;two—whole SARS-CoV-2 culture;and one—ACE2-expressing cancer cells. Essential oils may prevent the SARS-CoV-2 infection by targeting its receptors on the cells (ACE2 and TMPRSS2). Menthol, 1,8-cineole, and camphor are among the volatile compounds which serve as potential ACE2 blockers. β-caryophyllene may selectively target the SARS-CoV-2 spike protein and inhibit viral entry. Other interactions with SARS-CoV-2 proteases and RdRp are observed based on molecular docking. In conclusion, essential oils could target proteins related to the SARS-CoV-2 entry and replication. Further studies with improved and uniform study designs should be carried out to optimize essential oils as COVID-19 therapies. © 2023 by the authors.

Patient's experience and satisfaction with self-administered subcutaneous depot medroxyprogesterone acetate use during the first year of COVID-19.

OBJECTIVES: Self-administered subcutaneous (SC) depot medroxyprogesterone acetate (DMPA) can improve contraception access by eliminating a health center visit for administration. For patients at our New York City health centers who were offered a switch to self-administered DMPA-SC at the onset of the coronavirus 2019 (COVID-19) pandemic, we sought to understand their experience of choosing to switch, of accessing and using the method, and their method satisfaction. STUDY DESIGN: Individual interview study of 22 patients using intramuscular DMPA prior to the start of the pandemic. All had a telehealth visit to discuss switching to self-administered DMPA-SC and received a DMPA-SC prescription during the first months of COVID-19. We used a grounded theory analysis approach. RESULTS: Respondents viewed switching to self-administered DMPA-SC as a decision they had to make if they wanted to continue DMPA. Most respondents experienced logistical challenges acquiring DMPA-SC from their pharmacy. Issues around convenience were important to respondents; however what respondents found convenient varied. Despite all this, respondents appreciated having the option of DMPA-SC and felt it to be overall empowering. CONCLUSIONS: This study exploring patients' experience with self-administered DMPA-SC during the initial year of the COVID-19 pandemic found that, notwithstanding initial hesitation about self-administered injections and logistical challenges getting the SC formulation, many found the experience of trying self-administered DMPA-SC to be empowering and appreciated having this option. Thus, self-administered DMPA-SC should be included in clinicians' routine contraception counseling and provision, insurance companies should cover DMPA-SC without requiring prior authorization, and pharmacies should consistently stock DMPA-SC. IMPLICATIONS: Self-administered DMPA-SC is an acceptable contraception option that provides an opportunity to maintain contraception access while eliminating need for an in-person visit. Thus, self-administered DMPA-SC should be included in clinicians' routine contraception counseling and provision, insurance companies need to cover this contraceptive without need for prior authorization, and pharmacies should consistently stock DMPA-SC.

Comparing the efficacy of meglumine acridon acetate and pentanedioic acid imidazolyl ethanamide in the outpatient treatment for ARVI during the COVID-19 pandemic

This study compared the efficacy of different therapies for ARVI during the COVID-19 pandemic. Objective. To compare clinical efficacy of Cycloferon and Ingavirin in children aged 4–17 years treated in outpatient facilities during the epidemic season of СOVID-19. Patients and methods. This study included 101 patients who provided 143 oro-and nasopharyngeal swabs tested using certified PCR tests. Of them, 128 samples (89.5%) were positive, whereas 15 samples (10.5%) were negative. We identified the most common viruses circulating in January–May 2021, including (seasonal) coronaviruses (35.9%), rhinoviruses (20.3%), and other viruses. We also analyzed respiratory viruses that have circulated in Moscow during the last 6 years and found higher levels of seasonal coronaviruses. The most common ARVI symptoms in 2021 were fever, rhinitis, pharyngeal hyperemia, and fatigue. Fewer children had headache, cough, and enlarged lymph nodes. Results. We compared ARVI treatment with broad-spectrum antivirals in children aged between 4 and 17 years. Children in group 1 (n = 51) received Cycloferon®, while children in Group (n = 50) received Ingavirin®. Study participants were diagnosed with ARVI and moderate nasopharyngitis. Children from the Cycloferon group demonstrated a more significant dynamics of such clinical symptoms as headache (p < 0.05), cough (p < 0.01), rhinitis (p < 0.01), abundant mucus (p < 0.001), and enlarged lymph nodes (p < 0.001) than children from the Ingavirin group (there was a significant difference in the duration of these symptoms). Only 2 children from group 1 required antibiotics (3.4%), whereas in group 2, 11 children needed antibacterial therapy (22%).

Potential of a methanolic extract of Lawsonia inermis (L.) leaf as an alternative sanitiser in the time of COVID-19 Pandemic and beyond.

To harness the antimicrobial properties of a crude methanolic extract of Henna (Lawsonia inermis) leaf as a potential alternative sanitiser, there is the need to test its performance in different solutions. In this work, the effects of distilled water (dH20), Acetate-HCL (AH) Buffer (pH 4.6), Phosphate Buffer Saline (PBS) (pH 7.2) and Tris-HCL (TBH) Buffer (pH 8.6) on the antibacterial and antiviral activity of the extract were assessed. Through standard phytochemical screening and HPLC-MS (LCMS STANDARD 7.M), it was found that the extract consisted of about 30 different compounds including flavonoids. The extent of the antimicrobial activity of the extract in solutions was in the increasing order of AH > dH2O >>>> TBH > PBS. Under the same conditions, reduced antibacterial activity and complete cessation of the antiviral activity of the extract in TBH and PBS was observed. However, in AH and dH20, within 1-5 min, 1 mg ml-1, 0.125 mg ml-1 and 0.0625 mg ml-1 of the extract caused complete inactivation of E.coli (reductions of 8.2 log CFU ml-1), B. subtilis (reductions of 8.2 log CFU ml-1) and MS2 (reductions of 9.7 log PFU ml-1) respectively. The fluorescence microscopy images of the live/dead staining of the inactivated bacterial samples validated the extent of the inactivation. The broad spectrum and high antimicrobial activity of the extract, coupled with the plant not a staple food, has long history of safe use by humans as a medicine and cosmetic, cheaply available in abundance in many regions of the world, thus making the extract a potential candidate as an alternative sanitiser in the time of COVID-19 Pandemic and beyond.

Molecular Docking studies on the Anti-viral activity of Cellulose Acetate Phthalate (CAP) as an adjuvant against SARS-CoV-2 by Protease Mpro

Even after a year, the COVID-19 pandemic produced by the SARS-CoV-2 remains a major source of concerns for scientists. Surprisingly, the primary protease is a key target because of its role in viral propagation. No significant data is available regarding the off-label indications of pharmaceutical adjuvants so far. CAP stands for "Cellulose Acetate Phthalate", an industrial polymer utilized in the enteric coating of tablets and capsules. CAP has been shown in certain trials to have anti-HIV properties by using the co-receptor location. Thus, in the present work, CAP was used to test against SAR-primary CoV-2's protease Mpro using in-silico method. Auto Dock was used to evaluate selected CAP molecules against SAR-CoV-2, and Discovery studio visualizer was used to create 3D and 2D interaction photos. CAP's binding energies were-3.05kcal/mol,-3.78kcal/mol and-3.01kcal/mol during blind docking, site specific docking, and docking in presence of N3 inhibitor, respectively. Additionally, the discovery studio visualizer was utilized to observe the interacting amino acids with CAP structure. Interestingly, the data from the discovery studio visualizer showed that it established H-bonds with Mpro residues, TYR37, TYR101, and LYS100 during blind docking and LYS88, TYR101, and LYS100 during site specific docking. The findings indicated that CAP binds non-competitively to allosteric sites and that it may have synergistic effects with other anti-viral agents. Moreover, further research is required to justify its synergistic activity as anti-viral agent. Copyright © 2022, Anka Publishers. All rights reserved.

Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.

Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

A Simple and Cheap Method to Extract SARS-COV-2 Nucleic Acid from Nasopharyngeal Swab Without the Need Silica Filter Column

Background: The COVID-19 pandemic affected different aspects of human life seriously, including health issues. Unfortunately, the process of RNA extraction using commercial kits is highly expensive. Replacement of this technique with a cheaper one may help us catch a more affordable approach. Objectives: This study aims to introduce a simple and cost-benefit procedure to extract nucleic acid from swab samples of patients infected with SARS-COV-2. Methods: All 41 positive extracted samples were extracted with three methods separately. The first method was based on the commercial kit using a silica filter column. The second method was made of ammonium acetate, sodium acetate, and alcohol as an extraction solution, and the last method was applied using only the sodium acetate and alcohol solution. Results: All samples extracted with a commercial kit based on a silica column were positive (100%) with Cts 21 ± 4.9, 21.4 ± 4.8, and 28.1 ± 1.8 for RNA-dependent RNA polymerase (RdRp), N, and RNase P genes, respectively. In the precipitation method using ammonium acetate, 40 samples were detected positive (97.5%), and the Cts were 26.3 ± 4.5, 23.6 ± 5.3, and 25.7 ± 3.5 for the above three genes, respectively. Similar to the conventional extraction method, the third method also showed positive results (97.5%) significantly. The mean CTs were 26 ± 4.3, 23 ± 5.4, and 23.7 ± 2.3, respectively. Conclusions: Our results indicated that the precipitation method using ammonium acetate, sodium acetate, and ethanol could be an alternative extraction method instead of the column-based method for SARS-COV-2 by swab samples. © 2022, Author(s).

A review: The phytochemistry, pharmacology, and pharmacokinetics of Curcumae Longae Rhizoma (Turmeric)

Curcumae Longae Rhizoma (CLR) is the rhizome of Curcuma longa L. Pharmacological studies show that CLR can be used to treat cervical cancer, lung cancer, lupus nephritis, and other conditions. In this paper, we review botany, traditional application, phytochemistry, pharmacological activity, and pharmacokinetics of CLR. The literature from 1981 to date was entirely collected from online databases, such as Web of Science, Google Scholar, China Academic Journals full-text database (CNKI), Wiley, Springer, PubMed, and ScienceDirect. The data were also obtained from ancient books, theses and dissertations, and Flora Reipublicae Popularis Sinicae. There are a total of 275 compounds that have been isolated from CLR, including phenolic compounds, volatile oils, and others. The therapeutic effect of turmeric has been expanded from breaking blood and activating qi in the traditional sense to antitumor, anti-inflammatory, antioxidation, neuroprotection, antibacterial, hypolipidemic effects, and other benefits. However, the active ingredients and mechanisms of action related to relieving disease remain ill defined, which requires more in-depth research and verification at a clinical level.