Insights into targeting SARS-CoV-2: design, synthesis, in silico studies and antiviral evaluation of new dimethylxanthine derivatives.

Aiming to achieve efficient activity against severe acute respiratory syndrome coronavirus (SARS-CoV-2), the expansion of the structure- and ligand-based drug design approaches was adopted, which has been recently reported by our research group. Purine ring is a corner stone in the development of SARS-CoV-2 main protease (Mpro) inhibitors. The privileged purine scaffold was elaborated to achieve additional affinity based on hybridization and fragment-based approaches. Thus, the characteristic pharmacophoric features that are required for the inhibition of Mpro and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 were utilized along with the crystal structure information of both targets. The designed pathways involved rationalized hybridization with large sulfonamide moieties and a carboxamide fragment for the synthesis of ten new dimethylxanthine derivatives. The synthesis was performed under diverse conditions to afford N-alkylated xanthine derivatives, and cyclization afforded tricyclic compounds. Molecular modeling simulations were used to confirm and gain insights into the binding interactions at both targets' active sites. The merit of designed compounds and the in silico studies resulted in the selection of three compounds that were evaluated in vitro to estimate their antiviral activity against SARS-CoV-2 (compounds 5, 9a and 19 with IC50 values of 38.39, 8.86 and 16.01 µM, respectively). Furthermore, oral toxicity of the selected antiviral candidates was predicted, in addition to cytotoxicity investigations. Compound 9a showed IC50 values of 8.06 and 3.22 µM against Mpro and RdRp of SARS-CoV-2, respectively, in addition to promising molecular dynamics stability in both target active sites. The current findings encourage further specificity evaluations of the promising compounds for confirming their specific protein targeting.

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.

Anosmia and COVID-19

Introduction: Anosmia has been described as one of the characteristic symptoms of COVID-19 disease. It is even considered as a key marker for COVID-19 diagnosis. The aim of the study is to evaluate anosmia as prognostic factor in moderate and severe cases of COVID-19 patients. Method(s): Our study is a multicenter prospective study;300 patients were recruited and confirmed COVID-19 infection and admitted into 3 tertiary referral quarantine hospitals to receive medical treatment in Minia, Egypt. The study was conducted between April and October 2021. The selected random sample met the following inclusion criteria: adults older than 18 years, rhinopharyngeal swab positive for SARS-CoV-2 infection, and moderate and severe cases of COVID-19. The patients were subjected to the following protocol: full clinical history, general medical examination, otorhinolaryngological evaluation, mandatory swab for COVID-19, and recording of laboratory data. Patients underwent olfactory assessment and follow-up for 3 months. Olfactory assessment was done subjectively by odor recognition thresholds using L-butanol;after evaluation, the patients were divided into anosmic and nonanosmic groups. Collected data were compared and statistically analyzed. Result(s): Olfactory impairment was seen in 35% of moderate cases and 13% in severe cases. Our study revealed that patients with anosmia were younger and mostly female. Hospitalized patients with anosmia had a better prognosis. Our results showed no significant differences between the 2 groups regarding temperature, heart rate, and respiratory rate. Of patients with anosmia, 70% were associated with dysgeusia, and 50% recovered within 13 days while 85% recovered within 28 days. There was significant relationship (parallel relationship) between progress of anosmia and level of D-dimer, C-reactive protein, and serum ferritin. This indicateds that the prognosis of anosmia is highly related to the inflammatory process of COVID-19 pathophysiology. Conclusion(s): Anosmic patients with COVID-19 have more favorable prognosis and recovery than nonanosmic patients do, and anosmia improves with treatment of the disease.

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.

Rapid Detection of Coronavirus (COVID-19) Using Microwave Immunosensor Cavity Resonator.

This paper presents a rapid diagnostic device for the detection of the pandemic coronavirus (COVID-19) using a micro-immunosensor cavity resonator. Coronavirus has been declared an international public health crisis, so it is important to design quick diagnostic methods for the detection of infected cases, especially in rural areas, to limit the spread of the virus. Herein, a proof-of-concept is presented for a portable laboratory device for the detection of the SARS-CoV-2 virus using electromagnetic biosensors. This device is a microwave cavity resonator (MCR) composed of a sensor operating at industrial, scientific and medical (ISM) 2.45 GHz inserted in 3D housing. The changes of electrical properties of measured serum samples after passing the sensor surface are presented. The three change parameters of the sensor are resonating frequency value, amplitude and phase of the reflection coefficient |S11|. This immune-sensor offers a portable, rapid and accurate diagnostic method for the SARS-CoV-2 virus, which can enable on-site diagnosis of infection. Medical validation for the device is performed through biostatistical analysis using the ROC (Receiver Operating Characteristic) method. The predictive accuracy of the device is 63.3% and 60.6% for reflection and phase, respectively. The device has advantages of low cost, low size and weight and rapid response. It does need a trained technician to operate it since a software program operates automatically. The device can be used at ports' quarantine units, hospitals, etc.

Symptoms and blood character in COVID-19

Introduction: People with COVID-19 have had a wide range of symptoms, ranging from mild symptoms to severe illness. Symptoms may appear 2 to 14 days after exposure to the virus. COVID-19 is accompanied by specific changes in the circulating blood cells that are analyzed by a full blood count. The objective of this study is to evaluate symptoms and ratios between different blood cell in patients with COVID-19. Method: The study was done between June 2020 and December 2020 in the outpatient clinic of Minia University Hospital (tertiary hospital). A total of 33 patients with COVID- 19 and 33 controls were selected randomly from patients attending the otolaryngology (ORL) outpatient clinic. Both groups were matched in age and gender. Both groups were subjected to ORL and systematic examination;a blood sample was taken from each subject for complete blood count and C-reactive protein testing. We evaluated the white blood cell/ red blood cells ratio, neutrophils/lymphocyte ratio, platelets/ lymphocytes ratio, and lymphocyte/monocyte ratio. Computed tomography (CT) of the chest was also performed in all patients to assess chest condition. Results: Our data showed that anosmia was present in 55% of cases, burning sensation of the nose in 63.6%, nasal obstruction in 9%, fever in 57.6%, cough in 55.5%, burning of the throat in 45.5%, diarrhea in 9%, general fatigue in 75.8%, dysgusia in 51.6%, and elevated C-reactive protein in 66.7%. With regard to blood ratios, there was a negative correlation between study and control groups in all studied ratios. In all cases of anosmia and with other COVID-19 symptoms (excluding cases with cough), CT findings revealed inflammation of the lung (ground-glass appearance). Conclusion: COVID-19 infection results in otorhinolaryngological symptoms in variable numbers of patients and burning sensation of the nose is the most frequent symptom. Blood ratios were negatively correlated with the control group. CT chest is needed in cases without cough to avoid severe chest symptoms.

Automated Model for Tracking COVID-19 Infected Cases till Final Diagnosis

The COVID-19 pandemic is now devastating. It affects public safety and well-being. A crucial step in the COVID-19 battle will be tracking the positive cases with convenient accuracy of diagnosis. However, the time of pandemics shows the emergent need for automated diagnosis to support medical staff decisions in different steps of diagnosis and prognosis of target disease like medical imaging through X-rays, CT-Scans, etc. Besides laboratory investigation steps, we propose a system that provides an automated multi-stage decision system supported with decision causes using deep learning techniques for tracking cases of a target disease (COVID-19 in our paper). Encouraged by the open-source Data sets for COVID-19 infected patients' chest radiology, we proposed a system of three Consecutive stages. Each stage consists of a deep learning binary classifier tailored for the detection of a specific COVID-19 infection feature from chest radiology, either X-ray or CT-scan. By integrating the three classifiers, a multi-stage diagnostic system was attained that achieves an accuracy of (87.980 %), (78.717%), and (84%) for the three stages, respectively. By no means a productionready solution, our system will help in reducing errors caused by human decisions, taken under pressure, and exhausting routines, and it will be reliable to take urgent decisions once the model performance achieves the needed accuracy.

Sinapic Acid Suppresses SARS CoV-2 Replication by Targeting Its Envelope Protein

SARS CoV-2 is still considered a global health issue, and its threat keeps growing with the emergence of newly evolved strains. Despite the success in developing some vaccines as a protective measure, finding cost-effective treatments is urgent. Accordingly, we screened a number of phenolic natural compounds for their in vitro anti-SARS CoV-2 activity. We found sinapic acid (SA) selectively inhibited the viral replication in vitro with an half-maximal inhibitory concentration (IC₅₀) value of 2.69 microg/mL with significantly low cytotoxicity (CC₅₀ = 189.3 microg/mL). Subsequently, we virtually screened all currently available molecular targets using a multistep in silico protocol to find out the most probable molecular target that mediates this compound's antiviral activity. As a result, the viral envelope protein (E-protein) was suggested as the most possible hit for SA. Further in-depth molecular dynamic simulation-based investigation revealed the essential structural features of SA antiviral activity and its binding mode with E-protein. The structural and experimental results presented in this study strongly recommend SA as a promising structural motif for anti-SARS CoV-2 agent development.