Identification of FDA-approved drugs against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through computational virtual screening

The SARS-CoV-2 coronavirus is responsible for the COVID-19 outbreak, which overwhelmed millions of people worldwide; hence, there is an urgency to identify appropriate antiviral drugs. This study focuses on screening compounds that inhibit RNA-dependent RNA-polymerase (RdRp) essential for RNA synthesis required for replication of positive-strand RNA viruses. Computational screening against RdRp using Food and Drug Administration (FDA)-approved drugs identified ten prominent compounds with binding energies of more than − 10.00 kcal/mol, each a potential inhibitor of RdRp. These compounds’ binding energy is comparable to known RdRp inhibitors remdesivir (IC50 = 10.09 μM, SI = 4.96) and molnupiravir (EC50 = 0.67 − 2.66 µM) and 0.32–2.03 µM). Remdesivir and molnupiravir have been tested in clinical trial and remain authorized for emergency use in the treatment of COVID-19. In docking simulations, selected compounds are bound to the substrate-binding pocket of RdRp and showed hydrophobic and hydrogen bond interaction. For molecular dynamics simulation, capmatinib, pralsetinib, ponatinib, and tedizolid phosphate were selected from the initial ten candidate compounds. MD simulation indicated that these compounds are stable at 50-ns MD simulation when bound to RdRp protein. The screen hit compounds, remdesivir, molnupiravir, and GS-441524, are bound in the substrate binding pocket with good binding-free energy. As a consequence, capmatinib, pralsetinib, ponatinib, and tedizolid phosphate are potential new inhibitors of RdRp protein with potential of limiting COVID-19 infection by blocking RNA synthesis

A secure and lightweight drones-access protocol for smart city surveillance

The rising popularity of ICT and the Internet has enabled Unmanned Aerial Vehicle (UAV) to offer advantageous assistance to Vehicular Ad-hoc Network (VANET), realizing a relay node's role among the disconnected segments in the road. In this scenario, the communication is done between Vehicles to UAVs (V2U), subsequently transforming into a UAV-assisted VANET. UAV-assisted VANET allows users to access real-time data, especially the monitoring data in smart cities using current mobile networks. Nevertheless, due to the open nature of communication infrastructure, the high mobility of vehicles along with the security and privacy constraints are the significant concerns of UAV-assisted VANET. In these scenarios, Deep Learning Algorithms (DLA) could play an effective role in the security, privacy, and routing issues of UAV-assisted VANET. Keeping this in mind, we have devised a DLA-based key-exchange protocol for UAV-assisted VANET. The proposed protocol extends the scalability and uses secure bitwise XOR operations, one-way hash functions, including user's biometric verification when users and drones are mutually authenticated. The proposed protocol can resist many well-known security attacks and provides formal and informal security under the Random Oracle Model (ROM). The security comparison shows that the proposed protocol outperforms the security performance in terms of running time cost and communication cost and has effective security features compared to other related protocols

Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: a prospective genomic study

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen endemic to the Arabian Peninsula. Dromedary camels are a likely source of infection and the virus probably originated in Africa. We studied the genetic diversity, geographical structure, infection prevalence, and age-associated prevalence among camels at the largest entry port of camels from Africa into the Arabian Peninsula. METHODS: In this prospective genomic study, we took nasal samples from camels imported from Sudan and Djibouti into the Port of Jeddah in Jeddah, Saudi Arabia, over an almost 2-year period and local Arabian camels over 2 months in the year after surveillance of the port. We determined the prevalence of MERS-CoV infection, age-associated patterns of infection, and undertook phylogeographical and migration analyses to determine intercountry virus transmission after local lineage establishment. We compared all virological characteristics between the local and imported cohorts. We compared major gene deletions between African and Arabian strains of the virus. Reproductive numbers were inferred with Bayesian birth death skyline analyses. FINDINGS: Between Aug 10, 2016, and May 3, 2018, we collected samples from 1196 imported camels, of which 868 originated from Sudan and 328 from Djibouti, and between May 1, and June 25, 2018, we collected samples from 472 local camels, of which 189 were from Riyadh and 283 were from Jeddah, Saudi Arabia. Virus prevalence was higher in local camels than in imported camels (224 [47·5%] of 472 vs 157 [13·1%] of 1196; p<0·0001). Infection prevalence peaked among camels older than 1 year and aged up to 2 years in both groups, with 255 (66·9%) of 381 positive cases in this age group. Although the overall geographical distribution of the virus corresponded with the phylogenetic tree topology, some virus exchange was observed between countries corresponding with trade routes in the region. East and west African strains of the virus appear to be geographically separated, with an origin of west African strains in east Africa. African strains of the virus were not re-sampled in Saudi Arabia despite sampling approximately 1 year after importation from Africa. All local Arabian samples contained strains of the virus that belong to a novel recombinant clade (NRC) first detected in 2014 in Saudi Arabia. Reproduction number estimates informed by the sequences suggest sustained endemicity of NRC, with a mean Re of 1·16. INTERPRETATION: Despite frequent imports of MERS-CoV with camels from Africa, African lineages of MERS-CoV do not establish themselves in Saudi Arabia. Arabian strains of the virus should be tested for changes in virulence and transmissibility. FUNDING: German Ministry of Research and Education, EU Horizon 2020, and Emerging Diseases Clinical Trials Partnership

Room temperature magnetic phase transition in an electrically-tuned van der Waals ferromagnet

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room-temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr1.2Te2 observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8 * 10^21 cm^-3. We observed non-monotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr1.2Te2. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr1.2Te2 is a significant step towards practical spintronic devices.Comment: 18 pages, 4 figure

Diseño de un sistema de tratamiento de efluentes producidos por una empresa procesadora de productos lácteos

Trabajo de investigaciónEn el estudio se describirán una serie de análisis fisicoquímicos realizados al agua residual realizados a nivel de laboratorio a partir de la recolección de muestra de las empresas lácteas llamadas “San Jerónimo Cajicá Cabrera” y “Hermanos SAS”, ubicadas en Hato grande municipio de Cajicá. Para la propuesta del diseño de los equipos necesarios para el tratamiento de los efluentes líquidos de una planta procesadora lácteos.1. TITULO 2. LÍNEA DE INVESTIGACIÓN 3. OBJETIVOS 4. INTRODUCCIÓN 5. JUSTIFICACIÓN 6. ALCANCES Y LIMITACIONES 7. PL 8. MARCO DE REFERENCIA 9. MARCO METODOLÓGICO 10. CRONOGRAMA DE ACTIVIDADES 11. PRODUCTOS POR ENTREGAR 12. INSTALACIONES Y EQUIPO REQUERIDO 13. PRESUPUESTO DEL TRABAJO Y RECURSOS FINANCIEROS 14. ESTRATEGIAS DE COMUNICACIÓN Y DIVULGACIÓN 15. RESULTADOS Y DISCUSIÓN 16. CONCLUSIONES REFERENCIASPregradoIngeniero Civi

Prevalence, Clinical Characteristics and Determinants of Unsuccessful Treatment Outcomes Among Pulmonary Tuberculosis Patients: A 5-Year Registry-Based Retrospective Cohort Study

Hind M AlOsaimi,1 Mohammed K Alshammari,2 Ghadah K Almijlad,3 Nawaf M Alotaibi,3 Dhafer A Alqahtani,4 Mohammed M Alshamrani,5 Tariq A Shutur,6 Mansior F Alhazmi,6 Mohammed A Hurubi,6 Kutayd S ALShammari,6 Khalid M Alzahrani,7 Hadeel M Aldaghriri,7 Anood A Alshammari,8 Oudah S Alatawi,8 Reema A Alharbi9 1Department of Pharmacy Services Administration, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia; 2Department of Clinical Pharmacy, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia; 3Department of Clinical Pharmacy, Northern Border University, Rafha, Kingdom of Saudi Arabia; 4Department of Pharmacy, Security Forces Hospital, Riyadh, Kingdom of Saudi Arabia; 5Department of Respiratory Care, Northern Armed Area Forced Hospital, Hafar al Batin, Kingdom of Saudi Arabia; 6Department of Supply and Logistics, Northern Armed Area Forced Hospital, Hafar Al Batin, Kingdom of Saudi Arabia; 7Department of Radiology, Northern Armed Area Forced Hospital, Hafar Al Batin, Kingdom of Saudi Arabia; 8Pharmaceutical Services Department, Northern Area Armed Forces Hospital, King Khalid Military, Hafr Al Batin, Kingdom of Saudi Arabia; 9Department of Medicine, University of Tabuk, Tabuk, Saudi ArabiaCorrespondence: Mohammed K Alshammari, Department of Clinical Pharmacy, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia, Email [email protected]: Despite the existence of effective medications, pulmonary tuberculosis (PTB) remains a significant global public health concern, The evaluation and feedback of national TB control programs are crucial, requiring diligent monitoring of TB treatment outcomes and analysis of the factors influencing these outcomes. This study aims to provide valuable insights into the challenges faced by TB patients, which can inform better strategies for treatment and management in the future.Patients and Methods: We conducted a study in King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia (KSA), from January 1, 2018 to December 31, 2023. The study was a registry-based retrospective cohort study. Patients’ data were sourced from the National Tuberculosis Registry database of Saudi Arabia. Treatment outcomes were determined as either success or failure, considering clinical evaluation, changes in chest X-rays, and the results of subsequent sputum examinations during follow-up. To evaluate the data, SPSS version 28.0 was used.Results: A total of 427 PTB patients participated in the study. The results show successful treatment outcomes among 88.5% of patients. Among the patients, males exhibited a higher likelihood of treatment failure as compared to females (aOR 1.3; 95%Cl 1.2– 1.5, p < 0.001). Patients with positive sputum smear (aOR 1.3; 95%Cl 1.1– 1.3 p < 0.00) and the presence of cough were associated with an increased risk of treatment failure (aOR1.5; 95%Cl 1.1– 1.4, p < 0.001).Conclusion: This study shows that the percentage of unsuccessful treatment outcomes is high, ie, 11.5%, due to patients’ deaths and loss to follow-up. Enhanced supervision and treatment monitoring for tuberculosis patients at high risk of treatment failure can lead to improved treatment success rates in Saudi Arabia.Keywords: tuberculosis, treatment outcomes, retrospective study, Saudi Arabi

Is silicon a panacea for alleviating drought and salt stress in crops?

Salinity affects around 20% of all arable land while an even larger area suffers from recurrent drought. Together these stresses suppress global crop production by as much as 50% and their impacts are predicted to be exacerbated by climate change. Infrastructure and management practices can mitigate these detrimental impacts, but are costly. Crop breeding for improved tolerance has had some success but is progressing slowly and is not keeping pace with climate change. In contrast, Silicon (Si) is known to improve plant tolerance to a range of stresses and could provide a sustainable, rapid and cost-effective mitigation method. The exact mechanisms are still under debate but it appears Si can relieve salt stress via accumulation in the root apoplast where it reduces “bypass flow of ions to the shoot. Si-dependent drought relief has been linked to lowered root hydraulic conductance and reduction of water loss through transpiration. However, many alternative mechanisms may play a role such as altered gene expression and increased accumulation of compatible solutes. Oxidative damage that occurs under stress conditions can be reduced by Si through increased antioxidative enzymes while Si-improved photosynthesis has also been reported. Si fertilizer can be produced relatively cheaply and to assess its economic viability to improve crop stress tolerance we present a cost-benefit analysis. It suggests that Si fertilization may be beneficial in many agronomic settings but may be beyond the means of smallholder farmers in developing countries. Si application may also have disadvantages, such as increased soil pH, less efficient conversion of crops into biofuel and reduced digestibility of animal fodder. These issues may hamper uptake of Si fertilization as a routine agronomic practice. Here, we critically evaluate recent literature, quantifying the most significant physiological changes associated with Si in plants under drought and salinity stress. Analyses show that metrics associated with photosynthesis, water balance and oxidative stress all improve when Si is present during plant exposure to salinity and drought. We further conclude that most of these changes can be explained by apoplastic roles of Si while there is as yet little evidence to support biochemical roles of this element

HCV Infection among Saudi Population: High Prevalence of Genotype 4 and Increased Viral Clearance Rate

HCV is a major etiological agent of liver disease with a high rate of chronic evolution. The virus possesses 6 genotypes with many subtypes. The rate of spontaneous clearance among HCV infected individuals denotes a genetic determinant factor. The current study was designed in order to estimate the rate of HCV infection and ratio of virus clearance among a group of infected patients in Saudi Arabia from 2008 to 2011. It was additionally designed to determine the genotypes of the HCV in persistently infected patients. HCV seroprevalence was conducted on a total of 15,323 individuals. Seropositive individuals were tested by Cobas AmpliPrep/Cobas TaqMan HCV assay to determine the ratio of persistently infected patients to those who showed spontaneous viral clearance. HCV genotyping on random samples from persistently infected patients were conducted based on the differences in the 5′untranslated region (5′UTR). Anti-HCV antibodies were detected in 7.3% of the totally examined sera. A high percentage of the HCV infected individuals experienced virus clearance (48.4%). HCV genotyping revealed the presence of genotypes 1 and 4, the latter represented 97.6% of the tested strains. Evidences of the widespread of the HCV genotype 4 and a high rate of HCV virus clearance were found in Saudi Arabia