Corrigendum to "Quercitrin loaded cyclodextrin based nanosponge as a promising approach for management of lung cancer and COVID-19" [J. Drug Deliv. Sci. Technol. 77 (2022) 103921].

[This corrects the article DOI: 10.1016/j.jddst.2022.103921.].

Implication of nanotechnology to reduce the environmental risks of waste associated with the COVID-19 pandemic.

The COVID-19 pandemic is the largest global public health outbreak in the 21st century so far. It has contributed to a significant increase in the generation of waste, particularly personal protective equipment and hazardous medical, as it can contribute to environmental pollution and expose individuals to various hazards. To minimize the risk of infection, the entire surrounding environment should be disinfected or neutralized regularly. Effective medical waste management can add value by reducing the spread of COVID-19 and increasing the recyclability of materials instead of sending them to landfill. Developing an antiviral coating for the surface of objects frequently used by the public could be a practical solution to prevent the spread of virus particles and the inactivation of virus transmission. Relying on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to address this emergency. Here, through a multidisciplinary perspective encompassing various fields such as virology, biology, medicine, engineering, chemistry, materials science, and computer science, we describe how nanotechnology-based strategies can support the fight against COVID-19 well as infectious diseases in general, including future pandemics. In this review, the design of the antiviral coating to combat the spread of COVID-19 was discussed, and technological attempts to minimize the coronavirus outbreak were highlighted.

Discovery of Novel Thioquinazoline-N-aryl-acetamide/N-arylacetohydrazide Hybrids as Anti-SARS-CoV-2 Agents: Synthesis, in vitro Biological Evaluation, and Molecular Docking Studies.

In the current investigation, two novel series of (tetrahydro)thioquinazoline-N-arylacetamides and (tetrahydro)thioquinazoline-N-arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline-N-arylacetamide 17g as well as the tetrahydrothioquinazoline-N-arylacetohydrazides 18c and 18f showed potent antiviral activity with IC50 of 21.4, 38.45 and 26.4 µM, respectively. In addition, 18c and 18f demonstrated potential selectivity toward the SARS-CoV-2 over the host cells with SI of 10.67 and 16.04, respectively. Further evaluation of the mechanism of action of the three derivatives 17g, 18c, and 18f displayed that they can inhibit the virus at the adsorption as well as at the replication stages, in addition to their virucidal properties. In addition, 17g, 18c, and 18f demonstrated satisfactory physicochemical properties as well as drug-likeness properties to be further optimized for the discovery of novel antiviral agents. The docking simulation predicted the binding pattern of the target compounds rationalizing their differential activity based on their hydrophobic interaction and fitting in the hydrophobic S2 subsite of the binding site.

Investigating the Potential Anti-SARS-CoV-2 and Anti-MERS-CoV Activities of Yellow Necklacepod among Three Selected Medicinal Plants: Extraction, Isolation, Identification, In Vitro, Modes of Action, and Molecular Docking Studies.

The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5% and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2 activity of S. tomentosa was very high (100%) and anti-MERS-CoV inhibition was slightly lower (96%). Therefore, the phytochemical investigation of the very promising S. tomentosa L. led to the isolation and structural identification of nine compounds (1-9). Then, both the CC50 and IC50 values for the isolated compounds against SARS-CoV-2 were measured. Compound 4 (genistein 4'-methyl ether) achieved superior anti-SARS-CoV-2 activity with an IC50 value of 2.13 µm. Interestingly, the mode of action of S. tomentosa against SARS-CoV-2 showed that both virucidal and adsorption mechanisms were very effective. Additionally, the IC50 values of S. tomentosa against SARS-CoV-2 and MERS-CoV were found to be 1.01 and 3.11 µg/mL, respectively. In addition, all the isolated compounds were subjected to two separate molecular docking studies against the spike (S) and main protease (Mpr°) receptors of SARS-CoV-2.

Quercitrin loaded cyclodextrin based nanosponge as a promising approach for management of lung cancer and COVID-19.

Lung cancer and pandemic acute respiratory disease, COVID-19, are examples of the most worldwide widespread diseases. The aim of the current study is to develop cyclodextrin based nanosponge (CD-NS) for loading the flavonoid drug, quercitrin (QCT). This is to improve its solubility in an attempt to enhance its activity against lung cancer as well as SARS-CoV-2 virus responsible for COVID-19. Preparation of CD-NS was performed by ultrasound-assisted synthesis method. Two CDs were employed, namely, ß cyclodextrin (ßCD) and 2-hydroxy propyl-ß-cyclodextrin (2-HPßCD) that were crosslinked with diphenyl carbonate, one at a time. QCT loaded CD-NS revealed entrapment efficiency and particle size ranged between 94.17 and 99.03% and 97.10-325.90 nm, respectively. QCT loaded 2-HPßCD-NS revealed smaller particle size compared with that of QCT loaded ßCD-NS. Zeta potential absolute values of the prepared formulations were >20 mV, indicating physically stable nanosystems. The selected formulations were investigated by Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscopy which proved the formation of QCT loaded CD-NS exhibiting porous structure. QCT exhibited partial and complete amorphization in ßCD-NS and 2-HPßCD-NS, respectively. In vitro release revealed an improved release of QCT from CD-NS formulations. The biological activity of free QCT and QCT loaded CD-NS was investigated against lung cancer cell line A549 as well as SARS-CoV-2 virus. The results revealed that IC50 values of free QCT against lung cancer cell line A549 and SARS-CoV-2 were higher than those exhibited by QCT loaded CD-NS by 1.57-5.35 and 5.95-26.95 folds, respectively. QCT loaded 2-HPßCD-NS revealed enhanced in vitro release and superior biological activity compared with QCT loaded ßCD-NS.

Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies.

During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many of the FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro and remarkable efficacy against COVID-19 in clinical trials, no pharmaceutical products have yet been declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes for the treatment of depression, neuralgia, migraine prophylaxis, and eating disorders which are frequently reported symptoms in COVID-19 patients. Herein, the efficacy of eight frequently prescribed FDA-approved antidepressants on the inhibition of both SARS-CoV-2 and MERS-CoV was assessed. Additionally, the in vitro anti-SARS-CoV-2 and anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies have been performed for these drugs against the spike (S) and main protease (Mpro) pockets of both SARS-CoV-2 and MERS-CoV. Results showed that Amitriptyline, Imipramine, Paroxetine, and Sertraline had potential anti-viral activities. Our findings suggested that the aforementioned drugs deserve more in vitro and in vivo studies targeting COVID-19 especially for those patients suffering from depression.

Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study.

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2.

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.

New approach in SARS-CoV-2 surveillance using biosensor technology: a review.

Biosensors are analytical tools that transform the bio-signal into an observable response. Biosensors are effective for early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection because they target viral antigens to assess clinical development and provide information on the severity and critical trends of infection. The biosensors are capable of being on-site, fast, and extremely sensitive to the target viral antigen, opening the door for early detection of SARS-CoV-2. They can screen individuals in hospitals, airports, and other crowded locations. Microfluidics and nanotechnology are promising cornerstones for the development of biosensor-based techniques. Recently, due to high selectivity, simplicity, low cost, and reliability, the production of biosensor instruments have attracted considerable interest. This review article precisely provides the extensive scientific advancement and intensive look of basic principles and implementation of biosensors in SARS-CoV-2 surveillance, especially for human health. In this review, the importance of biosensors including Optical, Electrochemical, Piezoelectric, Microfluidic, Paper-based biosensors, Immunosensors, and Nano-Biosensors in the detection of SARS-CoV-2 has been underscored. Smartphone biosensors and calorimetric strips that target antibodies or antigens should be developed immediately to combat the rapidly spreading SARS-CoV-2. Wearable biosensors can constantly monitor patients, which is a highly desired feature of biosensors. Finally, we summarized the literature, outlined new approaches and future directions in diagnosing SARS-CoV-2 by biosensor-based techniques.

Determinants of having severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in Egypt.

BACKGROUND: Reported laboratory-confirmed COVID-19 cases underestimate the true burden of disease as cases without laboratory confirmation, and asymptomatic and mild cases are missed by local surveillance systems. Population-based seroprevalence studies can provide better estimates of burden of disease by taking into account infections that were missed by surveillance systems. Additionally, little is known about the determinants of seroconversion in community settings. METHODS: We conducted a cross-sectional serologic survey among 888 participants in Egypt. RESULTS: Neutralizing antibodies were detected in 30% of study volunteers. Age and educational level were associated with being seropositive as people older than 70 years and people with graduate degrees had lower seroprevalence. Self-reporting cases having COVID-19-related symptoms such as fever, malaise, headache, dyspnea, dry cough, chest pain, diarrhea, and loss of taste or smell were all associated with having antibodies. Fever and loss of taste or smell were strong predictors with odds ratios of 2.1 (95% confidence interval: 1.3-3.5) and 4.5 (95% confidence interval: 2.6-7.8), respectively. CONCLUSIONS: Our results can guide COVID-19 prevention and control policies and assist in determining the immunity level in some Egyptian communities.

Incidence, household transmission, and neutralizing antibody seroprevalence of Coronavirus Disease 2019 in Egypt: Results of a community-based cohort.

SARS-CoV-2 virus is transmitted in closed settings to people in contact with COVID-19 patients such as healthcare workers and household contacts. However, household person-to-person transmission studies are limited. Households participating in an ongoing cohort study of influenza incidence and prevalence in rural Egypt were followed. Baseline enrollment was done from August 2015 to March 2017. The study protocol was amended in April 2020 to allow COVID-19 incidence and seroprevalence studies. A total of 290 households including 1598 participants were enrolled and followed from April to October 2020 in four study sites. When a participant showed respiratory illness symptoms, a serum sample and a nasal and an oropharyngeal swab were obtained. Swabs were tested by RT-PCR for SARS-CoV-2 infection. If positive, the subject was followed and swabs collected on days three, six, nine, and 14 after the first swab day and a serum sample obtained on day 14. All subjects residing with the index case were swabbed following the same sampling schedule. Sera were collected from cohort participants in October 2020 to assess seroprevalence. Swabs were tested by RT-PCR. Sera were tested by Microneutralization Assay to measure the neutralizing antibody titer. Incidence of COVID-19, household secondary attack rate, and seroprevalence in the cohort were determined. The incidence of COVID-19 was 6.9% and the household secondary attack rate was 89.8%. Transmission within households occurred within two-days of confirming the index case. Infections were asymptomatic or mild with symptoms resolving within 10 days. The majority developed a neutralizing antibody titer by day 14 post onset. The overall seroprevalence among cohort participants was 34.8%. These results suggest that within-household transmission is high in Egypt. Asymptomatic or mild illness is common. Most infections seroconvert and have a durable neutralizing antibody titer.

Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies.

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world's population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects.

FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2.

(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.