The Impact of Vaccination on COVID-19 Pandemic in the Kurdistan Region of Iraq: A Mathematical Modelling

The spreading of COVID-19 became a global issue that had a significant impact on health, life, and economic sectors. Efforts from all over the world are focused on discussing a variety of healthcare approaches to reduce the effect of COVID-19 among individuals. Mathematical tools with numerical simulations are important approaches that help international efforts to determine critical transmission factors as well as controlling the virus spread. In this paper, we develop a mathematical model that considers a vaccination compartment in terms of ordinary differential equations. This study focuses on the real data of confirmed cases in Kurdistan Region of Iraq from July 17th, 2021 to January 1st, 2022. Model results and real data for the total number of infected people were compared using computational tools in MATLAB. Additionally, non-normalization, half-normalization, and full-normalization methods are used to determine the local sensitivities between model variables and parameters. Interestingly, computational results show that the dynamics of model results and real confirmed cases are very close to each other. Accordingly, the elasticity coefficients provide a great understanding of the impact of vaccination on transmissions. The model results here can also help international efforts for further suggestions and improvements to control this disease more effectively. © Palestine Polytechnic University-PPU 2023.

Exploring the volatile metabolites of three Chorisia species: Comparative headspace GC-MS, multivariate chemometrics, chemotaxonomic significance, and anti-SARS-CoV-2 potential.

Chorisia (syn. Ceiba) species are important ornamental, economic, and medicinal plants that are endowed with a diversity of secondary metabolites; however, their volatile organic compounds (VOCs) have been scarcely studied. Therefore, this work explores and compares the headspace floral volatiles of three common Chorisia species, namely Chorisia chodatii Hassl., Chorisia speciosa A. St.-Hil, and Chorisia insignis H.B.K. for the first time. A total of 112 VOCs of varied biosynthetic origins were identified at different qualitative and quantitative ratios, encompassing isoprenoids, fatty acid derivatives, phenylpropanoids, and others. Flowers of the investigated species showed perceptibly differentiated volatile profiles, with those emitted by C. insignis being dominated by non-oxygenated compounds (56.69 %), whereas oxygenated derivatives prevailed among the volatiles of C. chodatii (66.04 %) and C. speciosa (71.53 %). The variable importance in the projection (VIP) in the partial least-squares-discriminant (PLS-DA) analysis described 25 key compounds among the studied species, of which linalool was verified as the most important aroma compound based on VIP values and significance analysis, and it could represent the most typical VOC among these Chorisia species. Furthermore, molecular docking and dynamics analyses of both the major and the key VOCs displayed their moderate to promising binding interactions with four main proteins of SARS-CoV-2, including Mpro, PLpro, RdRp, and spike S1 subunit RBD. The current results collectively cast new light on the chemical diversity of the VOCs of Chorisia plants as well as their chemotaxonomic and biological relevance.

THE IMPACT OF THE CORONA PANDEMIC ON THE EDUCATIONAL TECHNOLOGY DIGITAL TRANSFORMATION STRATEGY IN THE KINGDOM OF SAUDI ARABIA

The research aimed to assess the educational digital transformation in the Kingdom of Saudi Arabia during the period of the Corona pandemic. By identifying the concept of digital transformation, analyzing the foundations and mechanisms to achieve educational digital transformation, the extent to which a qualified technological infrastructure exists, and analyzing digital transformation strategies in university institutions in the Kingdom. The quantitative analytical approach was used to examine the importance of the relationship between the readiness of the technological infrastructure and the mechanisms of the digital transformation of the educational environment. To achieve the research objectives, the questionnaire was used to collect data from the research community, which is represented by faculty members from Imam Abdul Rahman bin Faisal University, one of the educational institutions in the Kingdom of Saudi Arabia. The results showed that the Kingdom has a technological infrastructure capable of absorbing the digital educational transformation, as the digital educational transformation in the Kingdom during the Corona period has achieved effective results. There was also a significant relationship between the readiness of the technological infrastructure in the Kingdom and the implementation of the educational digital transformation strategy. The research revealed that there are significant differences in favor of the categories (Females-Doctorates-High Experience), towards the readiness of the infrastructure in the educational field capable of accommodating the educational digital transformation. We recommend adequate privacy and security measures to ensure that the learning process is fully digital. © ICAS 2022.

Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19.

BACKGROUND: COVID-19 has been frequently demonstrated to be associated with anosmia. Calcium cations are a mainstay in the transmission of odor. One of their documented effects is feedback inhibition. Thus, it has been advocated that reducing the free intranasal calcium cations using topical chelators such as pentasodium diethylenetriamine pentaacetate (DTPA) could lead to restoration of the olfactory function in patients with post-COVID-19 anosmia. METHODOLOGY: This is a randomized controlled trial that investigated the effect of DTPA on post-COVID-19 anosmia. A total of 66 adult patients who had confirmed COVID-19 with associated anosmia that continued beyond three months of being negative for SARS-CoV-2 infection. The included patients were randomly allocated to the control group that received 0.9 % sodium chloride-containing nasal spray or the interventional group that received 2 % DTPA-containing nasal spray at a 1:1 ratio. Before treatment and 30 days post-treatment, the patients' olfactory function was evaluated using Sniffin' Sticks, and quantitative estimation of the calcium cations in the nasal mucus was done using a carbon paste ion-selective electrode test. RESULTS: Patients in the DTPA-treated group significantly improved compared to the control group in recovery from functional anosmia to hyposmia. Additionally, they showed a significant post-treatment reduction in the calcium concentration compared to the control group. CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.

Network Meta-Analysis on the Mechanisms underlying Type 2 Diabetes Augmentation of COVID-19 Pathologies (preprint)

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. SARS-CoV-2 virus is internalized by surface receptors, e.g., angiotensin-converting enzyme-2 (ACE2). Clinical reports suggest that non-insulin dependent diabetes mellitus (DM-II) may enhance COVID-19. This study investigated how DM-II augments COVID-19 complications through molecular interactions with cytokines/chemokines, using QIAGEN Ingenuity Pathway Analysis (IPA) and CLC Genomics Workbench 22 (CLCG-22). RNA-sequencing of islet β-cell genomes through CLCG-22 (SRA SRP287500) were analyzed to identify differential expression of islet β-cell genes (Iβ-CG). IPA’s QIAGEN Knowledge Base (QKB) was also used to retrieve 88 total molecules shared between DM-II and SARS-CoV-2 infection to characterize and identify Iβ-CG, due to close association with DM-II. Molecules directly associated with ACE2 and cytokines/chemokines were also identified for their association with SARS-CoV-2 infection. Using IPA, 3 Iβ-CG in common with both diseases, SCL2A2, PPARγ, and CPLX8, were downregulated by DM-II. Their downregulation occurred due to increased activity of cytokines/chemokines and ACE2. Collectively, this network meta-analysis demonstrated that interaction of SARS-CoV-2 with ACE2 could primarily induce endothelial cell dysfunction. Identification of common molecules and signaling pathways between DM-II and SARS-CoV-2 infection in this study may lead to further discovery of therapeutic measures to simultaneously combat both diseases.

Green adherent spectrophotometric determination of molnupiravir based on computational calculations; application to a recently FDA-approved pharmaceutical dosage form.

Molnupiravir is an oral antiviral drug developed to provide significant benefit in reducing hospitalizations or deaths in mild COVID-19. Integrated green computational spectrophotometric method was developed for the determination of molnupiravir. Theoretical calculations were performed to predict the best coupling agent for efficient diazo coupling of molnupiravir. The binding energy between molnupiravir and various phenolic coupling agents, α-naphthol, ß-naphthol, 8-hydroxyquinoline, resorcinol, and phloroglucinol, was measured using Gaussian 03 software based on the density functional theory method and the basis set B3LYP/6-31G(d). The results showed that the interaction between molnupiravir and 8-hydroxyquinoline was higher than that of other phenolic coupling agents. The method described was based on the formation of a red colored chromogen by the diazo coupling of molnupiravir with sodium nitrite in acidic medium to form a diazonium ion coupled with 8-hydroxyquinoline. The absorption spectra showed maximum sharp peaks at 515 nm. The reaction conditions were optimized. Beer's law was followed over the concentration range of 1-12 µg/ml molnupiravir. Job's continuous variation method was developed and the stoichiometric ratio of molnupiravir to 8-hydroxyquinoline was determined to be 1:1. The described method was successfully applied to the determination of molnupiravir in pure form and in pharmaceutical dosage form. The results showed that the proposed method has minimal environmental impact compared to previous HPLC method.

'Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity': in-vitro and insilico studies.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predisposed to the emergence of worldwide catastrophe that impels the evolution of safe and effective therapeutic system. Polyphenols as resveratrol (RSV) exhibit a well evidenced antiviral activity. Unfortunately, like most phenolic nutraceuticals, RSV suffers from restrained solubility and massive degradation in GIT and liver which in turn prohibit its clinical use. Herein, PEGylated bilosomes (PBs) contain PEGylated edge activator along with the traditional components as (Span 60, cholesterol and bile salts) were proposed to boost both permeability and bioavailability of RSV. The investigation of the prominent effect of the diverse variables on the characteristics of the vesicles and picking of the optimum formula were conducted via construction of 23 factorial experiment. The appraisal of the formulae was conducted on the basis of entrapment efficiency percent (EE%), particle size (PS) and zeta potential (ZP). In addition, the spherical shaped optimal formula (F5) exhibited EE% of 86.1 ± 2.9%, PS of 228.9 ± 8.5 nm, and ZP of -39.8 ± 1.3 mV. The sorted optimum formula (F5) exhibited superior dissolution behaviors, and boosted Caco-2 cells cellular uptake by a round 4.7 folds relative to RSV dispersion. In addition, F5 demonstrated a complete in vitro suppression of SARS-CoV-2 at a concentration 0.48 µg/ml with 6.6 times enhancement in antiviral activity relative to RSV dispersion. The accomplished molecular modeling heavily provided proof for the possible interactions of resveratrol with the key residues of the SARS-CoV2 Mpro enzyme. Finally, F5 could be proposed as a promising oral panel of RSV for curation from SARS-CoV-2 infection.

Computational simulations of the effects of social distancing interventions on the COVID-19 pandemic

The spread of the COVID-19 pandemic has been considered as a global issue. Based on the reported cases and clinical data, there are still required international efforts and more preventative measures to control the pandemic more effectively. Physical contact between individuals plays an essential role in spreading the coronavirus more widely. Mathematical models with computational simulations are effective tools to study and discuss this virus and minimize its impact on society. These tools help to determine more relevant factors that influence the spread of the virus. In this work, we developed two computational tools by using the R package and Python to simulate the COVID-19 transmissions. Additionally, some computational simulations were investigated that provide critical questions about global control strategies and further interventions. Accordingly, there are some computational model results and control strategies. First, we identify the model critical factors that helps us to understand the key transmission elements. Model transmissions can significantly be changed for primary tracing with delay to isolation. Second, some types of interventions, including case isolation, no intervention, quarantine contacts and quarantine contacts together with contacts of contacts are analyzed and discussed. The results show that quarantining contacts is the best way of intervening to minimize the spread of the virus. Finally, the basic reproduction number R0 is another important factor which provides a great role in understanding the transmission of the pandemic. Interestingly, the current computational simulations help us to pay more attention to critical model transmissions and minimize their impact on spreading this disease. They also help for further interventions and control strategies.

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies.

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 Mpro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC50). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC50 value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC50 values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 Mpro enzyme was investigated by utilizing the SARS-CoV-2 Mpro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 Mpro inhibitory potential was attained for fondaparinux sodium with an IC50 value of 2.36 µM, surpassing the reference tipranavir (IC50 = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 Mpro inhibitory potential was attained for dabigatran with an IC50 value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.

Boosting the anti MERS-CoV activity and oral bioavailability of resveratrol via PEG-stabilized emulsomal nano-carrier: Factorial design, in-vitro and in-vivo assessments.

Resveratrol (RSV) is a phytoceutical polyphenolic compound exhibiting a well evidenced wide range of therapeutic activities. Unfortunately, its diminished aqueous solubility and extensive metabolism in gastro intestinal tract (GIT) and liver prohibit its biological activity and systemic availability. Herein the conducted study PEG stabilized emulsomes (PEMLs) were customized to enclose RSV aiming to boost its biological availability and antiviral activity. PEGylating the vesicles not only grant the promoted steric stability of the system but also being beneficial in exaggerating the intestinal permeability and extending the period of circulation of the drug, hence its targeted clinical use. The Investigation of the influence of predetermined variables on the physical characterization of formulae (entrapment efficiency EE%, particle size PS and zeta potential ZP) was implemented utilizing Design Expert® software. (F4) with desirability value (0.772), picked to be the optimal formula, which is fabricated utilizing 35 mg compritol as the lipidic core and 60 mg 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-Mpeg-2000). The dominance of the F4 relative to RSV dispersion was affirmed by the data acquired from ex-vivo and pharmacokinetic studies. In addition, F4 exhibited significant lower EC50 value (0.0127 µg/mL) relative to that of RSV dispersion(0.338 µg/mL) by around 26 times denoting the capability of the formulation to boost the antiviral activity. To a great extent, F4 was able to significantly suppress the inflammatory response and oxidative stress resulted from MERS-CoV infection on comparison with RSV dispersion. Finally, the potentiality of PEMLs as nano-panel with boosted both antiviral and oral bioavailability for RSV could be deduced based on the outcomes mentioned herein.

The Impact of Lifestyle Factors upon Illness Severity among Patients Infected with COVID-19

Background: COVID-19 infection have representing a wide range of clinical features and severity, some patients have mild symptoms, while othershave severe pneumonia. Several previous research findings analyzed and exposed the association between theseverityof COVID-19 and the contributing factors of this pandemic disease. This study was directed to investigate the impact of lifestyle factors onthe severity of illness among COVID-19 patients in Holy Kerbala City/ Iraq. Methods: A descriptive cross-sectional study was performed on 244 patients with COVID-19 by using a systematic random methodat Imam Hussein Medical City. The study was started from October-2021, to July-2022. A questionnaire involved three main parts: part one includes socio-demographic and medical data;the second part consists of 27 items, to measure the lifestyle factors, the third part includes the severity index of COVID-19. The data were collected through the interviewing technique, and the data were evaluated by using the IBM Statistical Package of Social Sciences (SPSS) program Version 26, both descriptive and inferential statistical procedurewere used to analyze the result of the study. Results: The results show that 51.6% of patients are within the age group ˃60 years with an MS±SD of 57.06 ± 19.203, 52.9% are males, 59.8% are from the urban area, 13.9% are smokers and 28.3% are previously smokers and 57.8% are not a smoker.80.7% have been exposed to first-time infection. Patients with COVID-19 are shown healthy in items related to diet and nutrition with MS±SD 2.78±0.262,substance use with MS±SD 3.77±0.306, sleep, social support, and environmental exposure. It is also representing an unhealthy lifestyle in the items related to physical activity MS±SD 1.62±0.844, and stress management MS±SD 2.48±0.330. In addition to that 48.4% had a critical level of illness severity, 24.6%, and 23.0% showed a high and a moderate level of illness severity respectively. There is a highly significant correlation found between lifestyle factors and illness severity among patients with COVID19 at a probability value of ≤0.01. Conclusion: The study concludes that an unhealthy lifestyle is related to physical activity, and stress management. A highly significant correlation is present between lifestyle factors and severity of illness among patients with COVID19.

Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study.

Like most of the RNA viruses, SARS-CoV-2 continuously mutates. Although many mutations have an insignificant impact on the virus properties, mutations in the surface protein, especially those in the receptor-binding domain, may lead to immune or vaccine escape variants, or altered binding activities to both the cell receptor and the drugs targeting such a protein. The current study intended to assess the ability of different variants of interest (VOIs) and variants of concern (VOCs) of SARS-CoV-2 for their affinities of binding to different repurposed drugs. Seven FDA approved drugs, namely, camostat, nafamostat mesylate, fenofibrate, umifenovir, nelfinavir, cefoperazone and ceftazidime, were selected based on their reported in vitro and clinical activities against SARA-CoV-2. The S1 protein subunit from eleven different variants, including the latest highly contiguous omicron variant, were used as targets for the docking study. The docking results revealed that all tested drugs possess moderate to high binding energies to the receptor-binding domain (RBD) of the S1 protein for all different variants. Cefoperazone was found to possess the highest binding energy to the RBD of the S1 protein of all the eleven variants. Ceftazidime was the second-best drug in terms of binding affinity towards the S1 RBD of the investigated variants. On the other hand, fenofibrate showed the least binding affinity towards the RBD of the S1 protein of all eleven variants. The binding affinities of anti-spike drugs varied among different variants. Most of the interacting amino acid residues of the receptor fall within the RBD (438-506).

Model predictions and data fitting can effectively work in spreading COVID-19 pandemic

Spreading COVID-19 pandemic has been considered as a global issue. Many international efforts including mathematical approaches have been recently discussed to control this disease more effectively. In this study, we have developed our previous SIUWR model and some transmission parameters are added. Accordingly, the basic reproduction number and elasticity coefficients are calculated at the equilibrium points. Then, some key critical model parameters are identified based on local sensitivities. In addition, the validation of the suggested model is checked by comparing some collected real data in Iraq and France from January 1st, 2021 to December 25th, 2021. Interestingly, there are good agreements between the model results and the real confirmed data using computational simulations in MATLAB. Results provide some biological interpretations and they can be used to control this pandemic more effectively. The model results will be used for both countries in minimizing the impact of this virus on their communities.

Olive Leaves as a Potential Phytotherapy in the Treatment of COVID-19 Disease; A Mini-Review.

Beginning from December 2019, widespread COVID-19 has caused huge financial misfortunes and exceptional wellbeing emergencies across the globe. Discovering an effective and safe drug candidate for the treatment of COVID-19 and its associated symptoms became an urgent global demand, especially due to restricted information that has been discharged with respect to vaccine efficacy and safety in humans. Reviewing the recent research, olive leaves were selected as a potential co-therapy supplement for the treatment and improvement of clinical manifestations in COVID-19 patients. Olive leaves were reported to be rich in phenolic compounds such as oleuropein, hydroxytyrosol, verbascoside, apigenin-7-O-glucoside, and luteolin-7-O-glucoside and also triterpenoids such as maslinic, ursolic, and oleanolic acids that have been reported as anti-SARS-CoV-2 metabolites in recent computational and in vitro studies. In addition, olive leaf extract was previously reported in several in vivo studies for its anti-inflammatory, analgesic, antipyretic, immunomodulatory, and antithrombotic activities which are of great benefit in the control of associated inflammatory cytokine storm and disseminated intravascular coagulation in COVID-19 patients. In conclusion, the described biological activities of olive leaves alongside their biosafety, availability, and low price make them a potential candidate drug or supplement to control COVID-19 infection and are recommended for clinical investigation.

Attitude towards COVID-19 vaccine among the general public in south India: A cross sectional study

Introduction: Coronavirus disease-19 (COVID-19) is a novel infection that sets off a pandemic in a short period. Research has been going on to develop safe and effective vaccines and around 150 are in the process of development. In India, two vaccines have been given emergency approval. There has been a rise in hesitancy toward vaccination not only in India but also worldwide. Materials and Methodology: The study included 697 participants who were not vaccinated. The study questionnaire was administered through online Google Forms and included informed consent, sociodemographic details, questions related to COVID-19 infection and vaccine, and vaccine attitude examination (VAX) scale. Results: Among the 697 participants, 216 (31%) were not willing to get vaccinated. Those with prevailing mental (P = 0.011) or physical health (P < 0.001) problems were of negative opinion toward vaccination because of unforeseen complications. Participants with lower education (P = 0.041), skilled to semi-skilled job (P = 0.028), and joint family (P = 0.006) opined that vaccination was more of commercial profiteering for manufacturing companies. Participants who were married (P = 0.010) and living in a joint family (P = 0.009) setting were more inclined toward a preference for natural immunity. Conclusion: The study highlights that 69% of participants were willing to take the COVID-19 vaccine. Various measures can be taken by different stakeholders to improve the positive attitude. As medical professions, we can improve the positive attitude by actively taking the vaccine and educating the local people about the benefits. © 2021 Archives of Mental Health ;Published by Wolters Kluwer - Medknow.