Hand and Wrist

Telemedicine was created to treat patients who were in remote places, far away from local health facilities or in areas with shortages of medical professionals. Its use is increasing nowadays especially in situations where distancing is essential as in Covid-19 pandemic. It is also increasingly becoming a tool for convenient medical care (Abboud et al., Clin Orthop Relat Res 435:250-257, 2005). Many disorders of the hand show a paucity of clinical signs as well as equivocal clinical tests that are difficult to perform. History taking is therefore essential in hand assessment not only in telemedicine settings, but in face-to-face assessments as well. To perform the exam, several specialized objects are required. This includes a desk, cotton, pen or pencil, key, bag, paper, and marker (Fig. 5.1). Through this chapter, we will introduce the role of telemedicine in assessment of hand through systematic virtual assessment that relies on three components: history, virtual examination, and investigations to reach the final diagnosis and hence the treatment. It is worth noting that face-to-face consultations should be the backup in case of failure to reach the definitive diagnosis as in complicated cases with different possible causalities of the condition. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022, corrected publication 2022.

Spine

With pandemic appearance of Covid-19, the keep of distancing becomes a standard measure to seize the infection spread. As the threats of pandemic progress have continued for months and probably may be for years, it is essential to validate existing tools to maintain the clinical assessment and, hence, patient treatment to avoid negative consequences of the lack of medical follow-up especially in patients of spine disorders. Therefore, establishment of a virtual assessment technique that can be conducted effectively is of outmost importance as a way of adaptation in the current situations. In this chapter, we conduct a systematic approach for the proper assessment of patients with spine disorders virtually using telemedicine (Dallolio et al., Arch Phys Med Rehabil 89(12):2332-2341, 2008;Patterson et al., Br J Neurosurg 14(6):552-554, 2000). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022, corrected publication 2022.

Introduction

The use of technology for healthcare-related communication grew historically out of a need to treat patients located in remote areas who were physically distant from appropriate healthcare facilities and qualified medical professionals. Since then, this practice of telemedicine has expanded to myriad other applications, especially as a tool for providing convenient medical care to the modern, digitally connected, on-the-go patient. For these patients, telemedicine is not only convenient and compatible with their lifestyle, but it also reduces time wasted in waiting rooms and provides more direct access to physician care for minor but urgent conditions (Matusitz and Breen, Health Commun 21(1):73-83, 2007;Wootton et al., Introduction to telemedicine, CRC Press, Boca Raton, 2017). With emergence of COVID-19 pandemic, the importance to keep healthcare under regulations of distancing increases the importance and the value of telemedicine. Orthopaedic surgery is one of the specialties that patients have to be followed on several occasions and can get many benefits of telemedicine especially in the current situation. In this chapter, historical hint as regard telemedicine, pros and cons, different applications, and how it helps both the physician and patient to cope with current difficult situations are described. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022, corrected publication 2022.

Impact of Covid-19 Pandemic on Emergency Nurses' Stress at King Salman Hospital in Hail, KSA

During the COVID-19 pandemic, nurses working in the clinical sector encountered a variety of challenges related to increased stress, which had an influence on the nurses' ability to provide care for patients. The Aim of study was to determine the impact of COVID-19 pandemic on emergency nurses' stress at the emergency department of King Salman Specialist Hospital in Hail, Saudi Arabia. A descriptive research design was utilized. Subjects included all available nurses who were working in the previous setting. The Instruments used in data collection consisted of the socio demographic data sheet of the studied nurses, the Perceived stress scale (PSS), and the nurses' pandemic-related experiences questionnaire (PREQ). The results revealed that, the studied nurses had experienced moderate stress regarding the PSS with total mean scores around "2” out of "4”. There was a significant statistical difference in the total mean scores of nurses' PREQ as regards to work status. The study concluded that, the COVID-19 Pandemic had increased the level of stress of the studied emergency nurses regardless their sociodemographic characteristics. © 2023 MEDIC SCIENTIFIC. All rights reserved.

Co-infection of COVID-19 patients with atypical bacteria: A study based in Jordan.

Objective: The aim of this work was to know the prevalence of Chlamydophila pneumoniae and Mycoplasma pneumoniae in coronavirus disease 2019 (COVID-19) patients in Jordan. Also, to assess a TaqMan real-time polymerase chain reaction (PCR) assay in detecting these two bacteria. Methods: This is a retrospective study performed over the last five months of the 2021. All nasopharyngeal specimens from COVID-19 patients were tested for C. pneumonia, and M. pneumoniae. The C. pneumoniae Pst-1 gene and M. pneumoniae P1 cytadhesin protein gene were the targets. Results: In this study, 14 out of 175 individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (8.0%) were co-infected with C. pneumoniae or M. pneumoniae. Co-infection with SARS-CoV-2 and C. pneumoniae was reported in 5 (2.9%) patients, while 9 (5.1%) patients had M. pneumoniae and SARS-CoV-2 co-infection. The mean (± std) of the correlation coefficient of the calibration curve for real-time PCR analysis was -0.993 (± 0.001) for C. pneumoniae and -0.994 (± 0.003) for M. pneumoniae. The mean amplification efficiencies of C. pneumoniae and M. Pneumoniae were 187.62% and 136.86%, respectively. Conclusion: In this first study based in Jordan, patients infected with COVID-19 have a low rate of atypical bacterial co-infection. However, clinicians should suspect co-infections with both common and uncommon bacteria in COVID-19 patients. Large prospective investigations are needed to give additional insight on the true prevalence of these co-infections and their impact on the clinical course of COVID-19 patients.

FDA approved drugs with antiviral activity against SARS-CoV-2: From structure-based repurposing to host-specific mechanisms.

The continuing heavy toll of the COVID-19 pandemic necessitates development of therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved drugs for inhibitory effects against main protease enzyme (Mpro) substrate-binding pocket of SARS-CoV-2 for non-covalent and covalent binding. Top candidates were screened against infectious SARS-CoV-2 in a cell-based viral replication assay. Promising candidates included atovaquone, mebendazole, ouabain, dronedarone, and entacapone, although atovaquone and mebendazole were the only two candidates with IC50s that fall within their therapeutic plasma concentration. Additionally, we performed Mpro assays on the top hits, which demonstrated inhibition of Mpro by dronedarone (IC50 18 µM), mebendazole (IC50 19 µM) and entacapone (IC50 9 µM). Atovaquone showed only modest Mpro inhibition, and thus we explored other potential mechanisms. Although atovaquone is Dihydroorotate dehydrogenase (DHODH) inhibitor, we did not observe inhibition of DHODH at the respective SARS-CoV-2 IC50. Metabolomic profiling of atovaquone treated cells showed dysregulation of purine metabolism pathway metabolite, where ecto-5'-nucleotidase (NT5E) was downregulated by atovaquone at concentrations equivalent to its antiviral IC50. Atovaquone and mebendazole are promising candidates with SARS-CoV-2 antiviral activity. While mebendazole does appear to target Mpro, atovaquone may inhibit SARS-CoV-2 viral replication by targeting host purine metabolism.

REDEFINING URBAN-RURAL BOUNDARIES FROM THE DIGITAL DISPARITY PERSPECTIVE

There is no international consensus on a comprehensive criterion to classify human settlements into urban and rural settlements. Different national criteria are used for delineating the borders between the two types of settlements. The main components of the criteria are population size, population density, population economic activity, administrative and legal and services and facilities. Whether all these criteria have been used or some of them, an outright socio-cultural and economic distinction between the two categories of settlements have developed over years around the world. The widely used virtual space during the pandemic provided people with access to facilities and services and enabled them to work for places that usually require their physical presence. The literature has not yet covered this point. Therefore, this paper aims at revisiting the classification of urban and rural areas in the COVID-19 aftermath. Through desk work and employing qualitative and quantitative research approaches, secondary data was collected from published relevant journals, reports, books, and websites. Content and comparative analysis for analysing qualitative data and content and quantitative comparative analysis and tabulation were used to carry out the research. This paper suggested that the world is in a transitional period towards full urban status. During this period, accessibility to virtual space can be used as a comprehensive criterion for calcifying human settlements into urban and rural. © 2022 by MIP.

SARS-CoV-2 vaccines from A to Z: A review of the current challenges

COVID-19 pandemic is a major worldwide health disaster firstly reported in December 2019. The Food and Drug Administration (FDA) has offered the public hope of halting it, authorizing vaccinations for emergency use with more than 85% efficacy against serious acute respiratory syndrome (SARS-CoV-2). Recent outbreaks of SARS-CoV-2 variations including spike-protein mutations, the key vaccines viral target for immune response, have prompted a thorough investigation into the vaccine's long-term effectiveness. Consequently, this review assayed the details on SARS-CoV-2 infection mechanism and how to control the infection by different types of SARS-CoV-2 vaccines, and their effectiveness against other mutant strains. Additionally, the review summarized the different complaints which have been recorded after vaccination. In conclusion, these negative effects must be constantly weighed against the predicted advantages in terms of disease prevention. Although COVID-19 vaccination is recommended for everyone aged 5 years and older, SARS-CoV-2 is high likely to continue to be a pandemic infectious as a result of the broadcasting of variants of the virus. Therefore, a booster vaccination, wearing a mask, and social distancing should be maintained. © 2023 Global NEST.

Identification of FDA Approved Drugs with Antiviral Activity against SARS-CoV-2: A Tale from structure-based drug repurposing to host-cell mechanistic investigation

The continuing heavy toll of the COVID-19 pandemic necessitates development of therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved drugs for inhibitory effects against main protease enzyme (Mpro) substrate-binding pocket of SARS-CoV-2 for non-covalent and covalent binding. Top candidates were screened against infectious SARS-CoV-2 in a cell-based viral replication assay. Promising candidates included atovaquone, mebendazole, ouabain, dronedarone, and entacapone, although atovaquone and mebendazole were the only two candidates with IC50s that fall within their therapeutic plasma concentration. Additionally, we performed Mpro assays on the top hits, which demonstrated inhibition of Mpro by dronedarone (IC50 18 µM), mebendazole (IC50 19 µM) and entacapone (IC50 9 µM). Atovaquone showed only modest Mpro inhibition, and thus we explored other potential mechanisms. Although atovaquone is Dihydroorotate dehydrogenase (DHODH) inhibitor, we did not observe inhibition of DHODH at the respective SARS-CoV-2 IC50. Metabolomic profiling of atovaquone treated cells showed dysregulation of purine metabolism pathway metabolite, showing that ecto-5′-nucleotidase (NT5E) is downregulated by atovaquone at concentrations equivalent to its antiviral IC50. Atovaquone and mebendazole are promising candidates targeting SARS-CoV-2, however atovaquone did not significantly inhibit Mpro at therapeutically meaningful concentrations but may inhibit SARS-CoV-2 viral replication by targeting host purine metabolism. Graphical

Atovaquone for treatment of COVID-19: A prospective randomized, double-blind, placebo-controlled clinical trial.

Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples. Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho -0.45, p = 0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho -0.54, p = 0.005). Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients.

Effect of COVID-19 Pandemic on Quality of Life Among Nursing Internship Students

Background: The Corona virus Disease 2019 (COVID-19) pandemic has exposed nurses, who are a very important group involved in the care of these patients, to many stresses that may affect their quality of life. Aim of the study was to assess effect of COVID-19 pandemic on quality of life among nursing internship students. Subjects and Methods: Research design: A descriptive design was used to conduct this study and to achieve the aim of this study. Setting(s): The study was carried out at Technical Institute of Nursing in Zagazig University. Subjects: A convenience sample of all available internship students (618 students) at the technical institute of nursing in Zagazig University. Tools of data collection: Two tools were used for data collection. Tool I: Structured Interviewing Questionnaire, General Characteristics of the nursing internship students, Tool II: The self-administered Quality of Life Evaluation Scale (QOLES). Result(s): 86.9% of the studied subjects had unsatisfactory quality of life,63.3% of studied subjects had information provided by faculty about COVID-19, while 57.4% of them attend lecture related COVID-19. In addition, 49.2% of studied subjects not able to deal with COVID-19. Conclusion(s): Most of studied subjects had unsatisfactory quality of life. Recommendations: Plans including proper multifaceted training programs and crisis management policies for such events should be adopted to minimize the physical and mental burdens on the nursing internship students. Copyright © 2022, Anka Publishers. All rights reserved.

Ivermectin role in COVID-19 treatment (IRICT): single-center, adaptive, randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: To investigate the efficacy and safety of ivermectin compared to hydroxychloroquine and placebo in hospitalized moderate to severe COVID-19 patients. RESEARCH DESIGN AND METHODS: The study was an adaptive, randomized, double-blinded, controlled, single-center trial. The study was a series of 3-arm comparisons between two different investigational therapeutic agents (ivermectin and hydroxychloroquine) and a placebo. There was interim monitoring to allow early stopping for futility, efficacy, or safety. RESULTS: Ivermectin decreased survival time from 29 to 18.3 days (HR, 9.8, 95%CI, 3.7-26.2), while it did not shorten the recovery time (HR, 1.02, 95%CI, 0.69-1.5). Subgroup analysis showed an association between ivermectin-related mortality and baseline oxygen saturation level. Moreover, stratified groups showed higher risk among patients on high flow O2. Hydroxychloroquine delayed recovery from 10.1 to 12.5 days (HR, 0.62, 95%CI, 0.4-0.95) and non-significantly decreased survival time from 29 to 26.8 days (HR, 1.47, 95%CI, 0.73-2.9). However, 3 months mortality rates were increased with hydroxychloroquine (RR, 2.05, 95%CI, 1.33-3.16). Neither ivermectin nor hydroxychloroquine increased adverse events and demonstrated safety profile compared to placebo. CONCLUSIONS: The study recommends against using either ivermectin or hydroxychloroquine for treatment of COVID-19 in hospitalized patients with any degree of severity. Clinical trial registration: www.clinicaltrials.gov identifier is: NCT04746365.

Feasibility of a Saliva-Based COVID-19 Screening Program in Abu Dhabi Primary Schools

Objective: The pandemic has forced closures of primary schools, resulting in loss of learning time on a global scale. In addition to face coverings, social distancing, and hand hygiene, an efficient testing method is important to mitigate the spread of COVID-19 in schools. We evaluated the feasibility of a saliva-based SARS-CoV-2 polymerase chain reaction testing program among 18 primary schools in the Emirate of Abu Dhabi, United Arab Emirates. Qualitative results show that children 4 to 5 years old had difficulty producing an adequate saliva specimen compared to those 6 to 12 years old. Methods: A short training video on saliva collection beforehand helps demystify the process for students and parents alike. Informed consent was challenging yet should be done beforehand by school health nurses or other medical professionals to reassure parents and maximize participation. Results: Telephone interviews with school administrators resulted in an 83% response rate. Overall, 93% of school administrators had a positive experience with saliva testing and felt the program improved the safety of their schools. The ongoing use of saliva testing for SARS-CoV-2 was supported by 73% of respondents. Conclusion: On-campus saliva testing is a feasible option for primary schools to screen for COVID-19 in their student population to help keep their campuses safe and open for learning.

Possible correlation between the probiotic activity of bacterial honey isolates and the in vitro inhibition of coronavirus 2 replication responsible for acute respiratory syndromes

Various strategies, like those using vaccines and antibiotics, have been examined for the prevention and treatment of virus's diseases, but until this moment infection control is not at sufficient level. Exopolysaccharides, especially from probiotics, became one of the most innovative approaches for antiviral agents. This research tried to highlight the effect of a probiotic polysaccharide, such as levan, in COVID-19 prevention. Accordingly, 5 levans types previously obtained from bacterial honey isolates were tested against COVID-19. The most promising result was recorded with levans from Pseudomonas aeruginosa HI1 (levAE) and Bacillus subtilis 9A (lev9A). The lowest cytotoxicity was obtained from lev9A (CC50=5.567e+006 mg/ml) and the most promising IC50 was obtained by levAE (10.75 mg/ml) followed by lev13M (142.5 mg/ml) then lev9A (1299 mg/ml). The dialysis process of levAE greatly affected the virus inhibition activity (IC50 of levAE/D =7.773e+006 mg/ml). Pseudomonas aeruginosa HI1 and Bacillus subtilis 9A were highly tolerant to the acidic (pHs 2, 3) and alkaline conditions (pHs 9, 11). Moreover, when incubated with 0.3 bile salt for 24h, their surviving rates recorded 94% and 100% respectively. H2O2 tolerance showed 77% surviving of Pseudomonas aeruginosa HI1 and 100% surviving of Bacillus subtilis 9A. The blood hemolysis and the antibiotics sensitivity tests confirmed the isolate's safety. The hypothesis that the isolates adhere to the lung cells, could explain the ability of the isolates and their levans to inhibit covid-19 replication. © 2022 National Information and Documentation Center.

Synthesis, crystal structure, and a molecular modeling approach to identify effective antiviral hydrazide derivative against the main protease of SARS-CoV-2.

In the fall of 2019, a new type of coronavirus took place in Wuhan city, China, and rapidly spread across the world and urges the scientific community to develop antiviral therapeutic agents. In our effort we have synthesized a new hydrazide derivative, (E)-N'-(1-(4-bromophenyl)ethylidene)-2-(6-methoxynaphthalen-2-yl)propanehydrazide for this purpose because of its potential inhibitory proprieties. The asymmetric unit of the title molecule consists of two independent molecules differing noticeably in conformation. In the crystal, the independent molecules are linked by N-H···O and C-H···O hydrogen bonds and C-H···π(ring) interactions into helical chains extending along the b-axis direction. The chains are further joined by additional C-H···π(ring) interactions into the full 3-D structure. To obtain a structure-activity relationship, the DFT-NBO analysis is performed to study the intrinsic electronic properties of the title compound. Molecular modeling studies were also conducted to examine the binding affinity of the compound for the SARS-CoV-2 main protease enzyme and to determine intermolecular binding interactions. The compound revealed a stable binding mode at the enzyme active pocket with a binding energy value of -8.1 kcal/mol. Further, stable dynamics were revealed for the enzyme-compound complex and reported highly favorable binding energies. The net MMGBSA binding energy of the complex is -37.41 kcal/mol while the net MMPBSA binding energy is -40.5 kcal/mol. Overall, the compound disclosed the strongest bond of ing the main protease enzyme and might be a good lead for further structural optimization.

Atovaquone for Treatment of COVID-19: A Prospective Randomized, Double-Blind, Placebo-Controlled Clinical Trial (preprint)

Background: An in-silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples. Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho -0.45, p=0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho -0.54, p= 0.005). Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients. clincialtrials.gov (NCT04456153).

THE EFFICIENCY OF SOME ACTIVE INGREDIENTS OF ARUM PALAESTINUM AS INHIBITORS TO 3CLPRO AND NSP15 PROTEINS

Two active coronaviral proteins (3CLpro and Nsp15) have been studied using both the GC-MS and docking methods. These coronaviral proteins have been examined with the methanol extract generated from leaves of the Arum palaestinum. According to the GC-MS findings, 19 major natural compounds are present in the plant’s methanolic extract. The lowest Binding Energy (LBE) and the inhibition constant (Ki) have been used to identify and classify the potential of these lead drugs with their pharmacological properties. The affinity of these compounds with coronaviral proteins has been evaluated to reveal the usage of these compounds at the active sites of the receptors, 3CLpro (PDB ID: 6LU7) and Nsp15 (PDB ID: 6VWW). The results of β-Sitosterol, Androstan-3-one, Phenobarbital, Maltose, and α-Tocopherol show more affinity to Nsp15 and 3CLpro than to the supporting control drugs. Furthermore, an evaluation of the interactions of these components with the amino acids of 3CLpro and Nsp15 revealed that β-Sitosterol has the best LBE score and Ki value as compared with those of the approved medication and all other compounds under investigation. Consequently, these potential compounds may be modern inhibitors of coronavirus. Further in vitro and in vivo studies are needed for such computational findings. © 2021 by Polish Pharmaceutical Society. This is an open-access article under the CC BY NC license (https://creativecommons.org/licenses/by-nc/4.0/).

Coding-complete genome sequences of two SARS-CoV-2 isolates from Egypt

This report announces the complete genome sequences of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates detected in Egypt. The isolates were obtained from oropharyngeal swab specimens from two Egyptians in Upper and Lower Egypt. Sequence analysis showed mutations that differentiate Egyptian strains from the reference strain 2019-nCoV WHU01.

Newly synthesized series of oxoindole-oxadiazole conjugates as potential anti-SARS-CoV-2 agents: in silico and in vitro studies

In this study, a series of 1,3,4-oxadiazoles carrying the isatin moiety (IVa-g) as anti-SARS-CoV-2 agents were designed and synthesized. Molecular docking of the compounds (IVa-g) into the SARS-CoV-2 M-pro active site showed promising binding affinities. The docking results were supported using molecular dynamics simulations and MM-GBSA calculations as well. To validate the in silico predictions, all compounds were evaluated for their half-maximal cytotoxicity (CC50) and virus-inhibitory (IC50) concentrations. The CC50 concentrations were remarkably high for most of the tested compounds. However, compounds IVe and IVg showed high activity against SARS-CoV-2 at IC50 values of 13.84 mu M and 4.63 mu M, with selectivity indices of 4.1 and 5.9, respectively. The most potent antiviral agent IVg demonstrated an IC50 of 16.6 mu M against SARS-CoV-2 M-pro, which is considered a moderate activity. However, the represented cellular antiviral activity of IVg could justify further optimization to develop this series of compounds as broad-spectrum anti-SARS-CoV-2 agents.

The Dual Therapeutic Effect Of Metformin Nuclei Based Drugs Modified With One Of Tulbaghia Violacea Extract Compounds (preprint)

Novel Schiff base was synthesized from condensation reaction of metformin with [4- (Diethylamino) benzaldehyde (NBM). Different metal complexes were prepared using Pd(II), Pt(II), Cu(II) and V(IV) metal ions. All complexes showed the non-electrolytic behavior. So, the expected molecular formulas for complexes are [Pd(NBM)Cl2], [Pt(NBM)Cl2], [Cu(NBM)2Cl2] and [VO(NBM)2]. The cytotoxicity of (NBM) Schiff base and its metal complexes on human cancer cell line, MCF-7, was investigated. V(IV) and Cu (II) complexes showed potential blood-glucose lowering effect higher than the commercial metformin drug. VO(IV) complex has superior antioxidant activity more than the other synthesized compounds and the standard ascorbic acid. Molecular docking investigation proved the presence of interesting interactions between all synthesized compounds with the active site amino acids of EGFR tyrosine kinase (anticancer activity). The molecular docking of metal complexes observed effective inhibition for the specific mTOR protein that is expected to aid the growth of the COVID-19 virus.