Descriptive Study Investigating Impact of Transition to Universal Health Insurance Coverage on Utilization of Healthcare in Sudan, 2016 - 2021

Objectives: Since 2016, Sudan was transitioning from limited healthcare subsidization to universal health coverage (UHC). Increasing healthcare access was widely considered beneficial, but some worried that UHC would overwhelm clinical services. In 2020 and 2021 UHC faced the challenge of Covid-19. We undertook a review of national healthcare utilization and enrolment data in order to better understand the impact of UHC in Sudan. Method(s): We conducted a descriptive study using National Health Insurance Fund databases. We analyzed annual enrolment, participating facilities, prescription volume and utilization from 2016 to 2021. Enrolment was stratified by employment status (government, informal sector, private sector, pensioner, impoverished). Utilization was assessed by type of care: primary, specialty, chronic disease and other;we calculated the ratio of primary to specialty care visits. We used the Mann-Kendall test for evaluating trends. Result(s): Participating facilities increased from 2,083 in 2016 to 3,549 in 2019, with slight contraction to 3,495 during 2020-21. Annual enrolment increased significantly, from 16.4 million in 2016 to 36.5 million in 2021 (p value < 0.01). The impoverished sector had the largest increase in enrolment (217%);informal sector had the lowest enrolment growth rate (7%). Volume of primary healthcare visits and prescriptions increased every year, except 2020, the first year of Covid-19 in Sudan. Specialty healthcare visits decreased over the same period, from 2,461,424 to 1,249,585 (p < 0.01). The ratio of primary to specialty visits increased from 6.0 in 2016 to 15.7 in 2021 (p < 0.001). Conclusion(s): In Sudan, transition to UHC increased utilization of primary care services, but at a slower rate than enrolment growth. The ratio of primary to specialty visits increased and specialty visits declined, suggesting that more primary care may have prevented specialist-requiring disease states and sequelae. Fears of overwhelming the health system were unfounded indicating that other barriers to healthcare might exist.Copyright © 2023

Targeting the omicron variant of SARS-CoV-2 with phytochemicals from Saudi medicinal plants: molecular docking combined with molecular dynamics investigations.

The new health crises caused by SARS-CoV-2 have resulted in millions of deaths worldwide. First discovered in November 2021, the omicron variant is more transmissible and is able to evade the immune system better than other previously identified SARS-CoV-2 variants, leading to a spike in cases. Great efforts have been made to discover inhibitors against SARS-CoV-2. Main protease (Mpro) inhibitors are considered promising anti-SARS-CoV-2 agents. The U.S. FDA has issued an Emergency Use Authorization for ritonavir-boosted nirmatrelvir. Nirmatrelvir is the first orally bioavailable inhibitor of SARS-CoV-2 Mpro. There is an urgent need to monitor the mutations and solve the problem of resistance, especially omicron Mpro, which contains one mutation - P132H. In the present study, 132,57 phytochemicals from 80 medicinal plants grown in Saudi Arabia were docked into the active site of Mpro omicron variant. Free binding energies were also calculated. This led to the discovery of five phytochemicals that showed better docking scores than the bound ligand nirmatrelvir. In addition, these molecules exhibited favorable free binding energies. The stability of compounds 1-5 with the protein was studied using molecular dynamics (MD) simulations. These compounds showed acceptable ADMET properties. The results were compared with the wild type. These candidates could be envisioned as new hits against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Discovery of novel potential inhibitors of TMPRSS2 and Mpro of SARS-CoV-2 using E-pharmacophore and docking-based virtual screening combined with molecular dynamic and quantum mechanics.

The pandemic of coronavirus disease is caused by the SARS-CoV-2 which is considered a global health issue. The main protease of COVID 19 (Mpro) has an important role in viral multiplication in the host cell. Inhibiting Mpro is a novel approach to drug discovery and development. Also, transmembrane serine proteases (TMPSS2) facilitate viral activation by cleavage S glycoproteins, thus considered one of the essential host factors for COVID-19 pathogenicity. Computational tools were widely used to reduce time and costs in search of effective inhibitors. A chemical library that contains over two million molecules was virtually screened against TMPRSS2. Also, XP docking for the top hits was screened against (Mpro) to identify dual-target inhibitors. Furthermore, MM-GBSA and predictive ADMET were performed. The top hits were further studied through density functional theory (DFT) calculation and showed good binding to the active sites. Moreover, molecular dynamics (MD) for the top hits were performed which gave information about the stability of the protein-ligand complex during the simulation period. This study has led to the discovery of potential dual-target inhibitors Z751959696, Z751954014, and Z56784282 for COVID-19 with acceptable pharmacokinetic properties. The outcome of this study can participate in the development of novel inhibitors to defeat SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Drug repurposing against main protease and RNA-dependent RNA polymerase of SARS-CoV-2 using molecular docking, MM-GBSA calculations and molecular dynamics.

A virus called severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) is the causing organism of coronavirus disease 2019 (COVID-19), which has severely affected human life and threatened public health. The pandemic took millions of lives worldwide and caused serious negative effects on human society and the economy. SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) are interesting targets due to their crucial role in viral replication and growth. Since there is only one approved therapy for COVID-19, drug repurposing is a promising approach to finding molecules with potential activity against COVID-19 in a short time and at minimal cost. In this study, virtual screening was performed on the ChEMBL library containing 9923 FDA-approved drugs, using various docking filters with different accuracy. The best drugs with the highest docking scores were further examined for molecular dynamics (MD) studies and MM-GBSA calculations. The results of this study suggest that nadide, cangrelor and denufosol are promising potential candidates against COVID-19. Further in vitro, preclinical and clinical studies of these candidates would help to discover safe and effective anti-COVID-19 drugs.

Discovery of novel TMPRSS2 inhibitors for COVID-19 using in silico fragment-based drug design, molecular docking, molecular dynamics, and quantum mechanics studies.

The global expansion of COVID-19 and the mutations of severe acute respiratory syndrome coronavirus necessitate quick development of treatment and vaccination. Because the androgen-responsive serine protease TMPRSS2 is involved in cleaving the SARS-CoV-2 spike protein allowing the virus to enter the cell, therefore, direct TMPRSS2 inhibition will inhibit virus activation and disease progression which make it an important target for drug discovery. In this study, a homology model of TMPRSS2 protein was initially developed. Then, we used the fragment-based drug design (FBDD) technique to develop effective TMPRSS2 inhibitors. Over a half-million fragments from the enamine database were screened for their binding ability to target protein, and then best-scoring fragments were linked to building new molecules with a good binding affinity. XP docking and MM-GBSA studies revealed 10 new formed molecules with docking score ≤ -14.982 kcal/mol compared to ambroxol (control) with a docking score of -6.464 kcal/mol. Finally, molecular dynamics (MD) and density functional theory (DFT) were calculated for the top 3 molecules.

Drug repurposing for SARS-CoV-2 main protease: Molecular docking and molecular dynamics investigations

The current novel corona virus illness (COVID-19) is a developing viral disease that was discovered in 2019. There is currently no viable therapeutic strategy for this illness management. Because traditional medication development and discovery has lagged behind the threat of emerging and re-emerging illnesses like Ebola, MERS-CoV, and, more recently, SARS-CoV-2. Drug developers began to consider drug repurposing (or repositioning) as a viable option to the more traditional drug development method. The goal of drug repurposing is to uncover new uses for an approved or investigational medicine that aren't related to its original use. The main benefits of this strategy are that there is less developmental risk and that it takes less time because the safety and pharmacologic requirements are met. The main protease (Mpro) of corona viruses is one of the well-studied and appealing therapeutic targets. As a result, the current research examines the molecular docking of Mpro (PDB ID: 5R81) conjugated repurposed drugs. 12,432 approved drugs were collected from ChEMBL and drugbank libraries, and docked separately into the receptor grid created on 5R81, using the three phases of molecular docking including high throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP). Based on docking scores and MM-GBSA binding free energy calculation, top three drugs (kanamycin, sulfinalol and carvedilol) were chosen for further analyses for molecular dynamic simulations. Graphical Image 1

Identification of novel TMPRSS2 inhibitors for COVID-19 using e-pharmacophore modelling, molecular docking, molecular dynamics and quantum mechanics studies.

SARS coronavirus 2 (SARS-CoV-2) has spread rapidly around the world and continues to have a massive global health effect, contributing to an infectious respiratory illness called coronavirus infection-19 (COVID-19). TMPRSS2 is an emerging molecular target that plays a role in the early stages of SARS-CoV-2 infection; hence, inhibiting its activity might be a target for COVID-19. This study aims to use many computational approaches to provide compounds that could be optimized into clinical candidates. As there is no experimentally derived protein information, initially we develop the TMPRSS2 model. Then, we generate a pharmacophore model from TMPRSS2 active site consequently, and the developed models were employed for the screening of one million molecules from the Enamine database. The created model was then screened using e-pharmacophore-based screening, molecular docking, free energy estimation and molecular dynamic simulation. Also, ADMET prediction and density functional theory calculations were performed. Three potential molecules (Z126202570, Z46489368, and Z422255982) exhibited promising stable binding interactions with the target. In conclusion, these findings empower further in vitro and clinical assessment for these compounds as novel anti-COVID19 agents.

Impact of wearing personal protective equipment on the performance and decision making of surgeons during the COVID-19 pandemic: An observational cross-sectional study.

ABSTRACT: During the coronavirus disease 2019 (COVID-19) pandemic, the mandatory use of personal protective equipment (PPE) has resulted in a significant reduction in the infection rate among health care workers (HCWs). However, there are some ongoing concerns about the negative impact of using PPE for prolonged periods.This study examined the impact of wearing PPE on surgeons' performance and decision making during the COVID-19 pandemic.In this cross-sectional study, an anonymous online questionnaire was created and disseminated to surgeons all over the Eastern Province of Saudi Arabia. The questionnaire included the demographic data, the local hospital policies, the non-technical skills (e.g., communication, vision, and comfort) and the technical skills, and the process of decision making.From June 2020 to August 2020, 162 surgeons participated in this questionnaire. Of them, 80.2% were aged from 26 to 45 years, 70.4% have received a special training for PPE, and 59.3% of participants have operated on COVID-19 confirmed cases. A negative impact of wearing PPE was reported on their overall comfort, vision, and communication skills (92.6%, 95.1%, and 82.8%, respectively). The technical skills and decision making were not significantly affected (60.5% and 72.8%, respectively). More preference for conservative approach, damage control procedures, and/or open approach was reported.Despite its benefits, PPE is associated with a significant negative impact on the non-technical skills (including vision, communication, and comfort) as well as a non-significant negative impact on technical skills and decision making of surgeons. Extra efforts should be directed to improve PPE, especially during lengthy pandemics.

Identification of novel transmembrane Protease Serine Type 2 drug candidates for COVID-19 using computational studies.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergence has resulted in a global health crisis. As a consequence, discovering an effective therapy that saves lives and slows the spread of the pandemic is a global concern currently. In silico drug repurposing is highly regarded as a precise computational method for obtaining fast and reliable results. Transmembrane serine-type 2 (TMPRSS2) is a SARS CoV-2 enzyme that is essential for viral fusion with the host cell. Inhibition of TMPRSS2 may block or lessen the severity of SARS-CoV-2 infection. In this study, we aimed to perform an in silico drug repurposing to identify drugs that can effectively inhibit SARS-CoV-2 TMPRSS2. As there is no 3D structure of TMPRSS2 available, homology modeling was performed to build the 3D structure of human TMPRSS2. 3848 world-approved drugs were screened against the target. Based on docking scores and visual outcomes, the best-fit drugs were chosen. Molecular dynamics (MD) and density functional theory (DFT) studies were also conducted. Five potential drugs (Amikacin, isepamicin, butikacin, lividomycin, paromomycin) exhibited promising binding affinities. In conclusion, these findings empower purposing these agents.

The Recombination Potential between SARS-CoV-2 and MERS-CoV from Cross-Species Spill-over Infections.

Countries in the Middle-East (ME) are tackling two corona virus outbreaks simultaneously, Middle-Eastern Respiratory Syndrome Coronavirus (MERS-CoV) and the current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Both viruses infect the same host (humans) and the same cell (type-II alveolar cells) causing lower respiratory illnesses such as pneumonia. Molecularly, MERS-CoV and SARS-CoV-2 enter alveolar cells via spike proteins recognizing dipeptidyl peptidase-4 and angiotensin converting enzyme-II, respectively. Intracellularly, both viruses hide in organelles to generate negative RNA strands and initiate replication using very similar mechanisms. At the transcription level, both viruses utilise identical Transcription Regulatory Sequences (TRSs), which are known recombination cross-over points during replication, to transcribe genes. Using whole genome alignments of both viruses, we identify clusters of high sequence homology at ORF1a and ORF1b. Given the high recombination rates detected in SARS-CoV-2, we speculate that in co-infections recombination is feasible via TRS and/or clusters of homologies. Accordingly, here we recommend mitigation measure and testing for both MERS-CoV and SARS-CoV-2 in ME countries.