A review on computer-aided chemogenomics and drug repositioning for rational COVID-19 drug discovery.

Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants.

CaZnO-based nanoghosts for the detection of ssDNA, pCRISPR and recombinant SARS-CoV-2 spike antigen and targeted delivery of doxorubicin.

Overexpression of proteins/antigens and other gene-related sequences in the bodies could lead to significant mutations and refractory diseases. Detection and identification of assorted trace concentrations of such proteins/antigens and/or gene-related sequences remain challenging, affecting different pathogens and making viruses stronger. Correspondingly, coronavirus (SARS-CoV-2) mutations/alterations and spread could lead to overexpression of ssDNA and the related antigens in the population and brisk activity in gene-editing technologies in the treatment/detection may lead to the presence of pCRISPR in the blood. Therefore, the detection and evaluation of their trace concentrations are of critical importance. CaZnO-based nanoghosts (NGs) were synthesized with the assistance of a high-gravity technique at a 1,800 MHz field, capitalizing on the use of Rosmarinus officinalis leaf extract as the templating agent. A complete chemical, physical and biological investigation revealed that the synthesized NGs presented similar morphological features to the mesenchymal stem cells (MSCs), resulting in excellent biocompatibility, interaction with ssDNA- and/or pCRISPR-surface, through various chemical and physical mechanisms. This comprise the unprecedented synthesis of a fully inorganic nanostructure with behavior that is similar to MSCs. Furthermore, the endowed exceptional ability of inorganic NGs for detective sensing/folding of ssDNA and pCRISPR and recombinant SARS-CoV-2 spike antigen (RSCSA), along with in-situ hydrogen peroxide detection on the HEK-293 and HeLa cell lines, was discerned. On average, they displayed a high drug loading capacity of 55%, and the acceptable internalizations inside the HT-29 cell lines affirmed the anticipated MSCs-like behavior of these inorganic-NGs.

COVID-19 immunotherapy: Treatment based on the immune cell-mediated approaches.

Multiple efforts are currently underway to control and treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide. Despite all efforts, the virus that emerged in Wuhan city has rapidly spread globally and led to a public health emergency of international concern (PHEIC) due to the lack of approved antiviral therapy. Nevertheless, SARS-CoV-2 has had a significant influence on the evolution of cellular therapeutic approaches. Adoptive immune cell therapy is innovative and offers either promising prophylactic or therapy for patients with moderate-to-severe COVID-19. This approach is aimed at developing safety and providing secure and effective therapy in combination with standard therapy for all COVID-19 infected individuals. Based on the effective results of previous studies on both inflammatory and autoimmune diseases, various immune cell therapies against COVID-19 have been reviewed and discussed. It must be considered that the application of cell therapy for treatment and to eliminate infected respiratory cells could result in excessive inflammation, so this treatment must be used in combination with other treatments, despite its many beneficial efforts.

Bioactive hybrid metal-organic framework (MOF)-based nanosensors for optical detection of recombinant SARS-CoV-2 spike antigen.

Fast, efficient, and accurate detection of SARS-CoV-2 spike antigen is pivotal to control the spread and reduce the mortality of COVID-19. Nevertheless, the sensitivity of available nanobiosensors to detect recombinant SARS-CoV-2 spike antigen seems insufficient. As a proof-of-concept, MOF-5/CoNi2S4 is developed as a low-cost, safe, and bioactive hybrid nanostructure via the one-pot high-gravity protocol. Then, the porphyrin, H2TMP, was attached to the surface of the synthesized nanomaterial to increase the porosity for efficient detection of recombinant SARS-CoV-2 spike antigen. AFM results approved roughness in different ranges, including 0.54 to 0.74 µm and 0.78 to ≈0.80 µm, showing good physical interactions with the recombinant SARS-CoV-2 spike antigen. MTT assay was performed and compared to the conventional synthesis methods, including hydrothermal, solvothermal, and microwave-assisted methods. The synthesized nanodevices demonstrated above 88% relative cell viability after 24 h and even 48 h of treatment. Besides, the ability of the synthesized nanomaterials to detect the recombinant SARS-CoV-2 spike antigen was investigated, with a detection limit of 5 nM. The in-situ synthesized nanoplatforms exhibited low cytotoxicity, high biocompatibility, and appropriate tunability. The fabricated nanosystems seem promising for future surveys as potential platforms to be integrated into biosensors.

The impact of protein corona on the biological behavior of targeting nanomedicines.

For successful translation of targeting nanomedicines from bench to bedside, it is vital to address their most common drawbacks namely rapid clearance and off-target accumulation. These complications evidently originate from a phenomenon called "protein corona (PC) formation" around the surface of targeting nanoparticles (NPs) which happens once they encounter the bloodstream and interact with plasma proteins with high collision frequency. This phenomenon endows the targeting nanomedicines with a different biological behavior followed by an unexpected fate, which is usually very different from what we commonly observe in vitro. In addition to the inherent physiochemical properties of NPs, the targeting ligands could also remarkably dictate the amount and type of adsorbed PC. As very limited studies have focused their attention on this particular factor, the present review is tasked to discuss the best simulated environment and latest characterization techniques applied to PC analysis. The effect of PC on the biological behavior of targeting NPs engineered with different targeting moieties is further discussed. Ultimately, the recent progresses in manipulation of nano-bio interfaces to achieve the most favorite therapeutic outcome are highlighted.

Quantum dots against SARS-CoV-2: diagnostic and therapeutic potentials.

The application of quantum dots (QDs) for detecting and treating various types of coronaviruses is very promising, as their low toxicity and high surface performance make them superior among other nanomaterials; in conjugation with fluorescent probes they are promising semiconductor nanomaterials for the detection of various cellular processes and viral infections. In view of the successful results for inhibiting SARS-CoV-2, functional QDs could serve eminent role in the growth of safe nanotherapy for the cure of viral infections in the near future; their large surface areas help bind numerous molecules post-synthetically. Functionalized QDs with high functionality, targeted selectivity, stability and less cytotoxicity can be employed for highly sensitive co-delivery and imaging/diagnosis. Besides, due to the importance of safety and toxicity issues, QDs prepared from plant sources (e.g. curcumin) are much more attractive, as they provide good biocompatibility and low toxicity. In this review, the recent developments pertaining to the diagnostic and inhibitory potentials of QDs against SARS-CoV-2 are deliberated including important challenges and future outlooks. © 2022 Society of Chemical Industry (SCI).

Porphyrin Molecules Decorated on Metal-Organic Frameworks for Multi-Functional Biomedical Applications.

Metal-organic frameworks (MOFs) have been widely used as porous nanomaterials for different applications ranging from industrial to biomedicals. An unpredictable one-pot method is introduced to synthesize NH2-MIL-53 assisted by high-gravity in a greener media for the first time. Then, porphyrins were deployed to adorn the surface of MOF to increase the sensitivity of the prepared nanocomposite to the genetic materials and in-situ cellular protein structures. The hydrogen bond formation between genetic domains and the porphyrin' nitrogen as well as the surface hydroxyl groups is equally probable and could be considered a milestone in chemical physics and physical chemistry for biomedical applications. In this context, the role of incorporating different forms of porphyrins, their relationship with the final surface morphology, and their drug/gene loading efficiency were investigated to provide a predictable pattern in regard to the previous works. The conceptual phenomenon was optimized to increase the interactions between the biomolecules and the substrate by reaching the limit of detection to 10 pM for the Anti-cas9 protein, 20 pM for the single-stranded DNA (ssDNA), below 10 pM for the single guide RNA (sgRNA) and also around 10 nM for recombinant SARS-CoV-2 spike antigen. Also, the MTT assay showed acceptable relative cell viability of more than 85% in most cases, even by increasing the dose of the prepared nanostructures.

The quest for a better fight: How can nanomaterials address the current therapeutic and diagnostic obstacles in the fight against COVID-19?

The inexorable coronavirus disease 2019 (COVID-19) pandemic with around 226 million people diagnosed and approximately 4.6 million deaths, is still moving toward more frightening statistics, calling for the urgent need to explore solutions for the current challenges in therapeutic and diagnostic approaches. The challenges associated with existing therapeutics in COVID-19 include lack of in vivo stability, efficacy, and safety. Nanoparticles (NPs) can offer a handful of tools to tackle these problems by enabling efficacious and safe delivery of both virus- and host-directed therapeutics. Furthermore, they can enable maximized clinical outcome while eliminating the chance of resistance to therapy by tissue-targeting and concomitant delivery of multiple therapeutics. The promising application of NPs as vaccine platforms is reflected by the major advances in developing novel COVID-19 vaccines. Two of the most critical COVID-19 vaccines are mRNA-based vaccines delivered via NPs, making them the first FDA-approved mRNA vaccines. Besides, NPs have been deployed as simple, rapid, and precise tools for point of care disease diagnosis. Not enough said NPs can also be exploited in novel ways to expedite the drug discovery process. In light of the above, this review discusses how NPs can overcome the hurdles associated with therapeutic and diagnostic approaches against COVID-19.

SARS-Cov-2 and COVID-19, Basic and Clinical Aspects of the Human Pandemic: A Review.

In the last two decades, we have witnessed three major epidemics of the coronavirus human disease namely, severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome, and more recently an ongoing global pandemic of coronavirus disease 2019 (COVID-19). Iran, a country of nearly 84 million, in the Middle East, severely involved with the COVID-19 disease. A documented multidimensional approach to COVID-19 disease is therefore mandatory to provide a well-balanced platform for the concerned medical community in our county and beyond. In this review, we highlight the disease status in Iran and attempt to provide a multilateral view of the fundamental and clinical aspects of the disease including the clinical features of the confirmed cases, virology, pathogenesis, epidemiology, and laboratory methods needed for diagnosis.

Baricitinib: From Rheumatoid Arthritis to COVID-19.

Baricitinib is a JAK1/2 inhibitor that was first approved for treating moderate to severe rheumatoid arthritis (RA) but that later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. There is a growing body of evidence, obtained from clinical trials and case reports, demonstrating clinical and paraclinical improvement in patients following administration of baricitinib including RA, systemic lupus erythematosus, psoriasis, atopic dermatitis, alopecia areata, interferon-mediated autoinflammatory diseases, graft-versus-host disease, diabetic kidney disease, and, recently, coronavirus disease-19. However, despite overall encouraging results, many adverse effects have been observed in baricitinib-treated patients, ranging from simple infections to increased risk of malignancies, particularly in long-term use. The significant efficacy of baricitinib, versus the probable adverse effects, urge further investigation before establishing it as a part of standard therapeutic protocols. Here, we have provided a review of the studies that have used baricitinib for treating various inflammatory disorders and summarized the advantages and disadvantages of its administration.

Point-of-Use Rapid Detection of SARS-CoV-2: Nanotechnology-Enabled Solutions for the COVID-19 Pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic that has been spreading around the world since December 2019. More than 10 million affected cases and more than half a million deaths have been reported so far, while no vaccine is yet available as a treatment. Considering the global healthcare urgency, several techniques, including whole genome sequencing and computed tomography imaging have been employed for diagnosing infected people. Considerable efforts are also directed at detecting and preventing different modes of community transmission. Among them is the rapid detection of virus presence on different surfaces with which people may come in contact. Detection based on non-contact optical techniques is very helpful in managing the spread of the virus, and to aid in the disinfection of surfaces. Nanomaterial-based methods are proven suitable for rapid detection. Given the immense need for science led innovative solutions, this manuscript critically reviews recent literature to specifically illustrate nano-engineered effective and rapid solutions. In addition, all the different techniques are critically analyzed, compared, and contrasted to identify the most promising methods. Moreover, promising research ideas for high accuracy of detection in trace concentrations, via color change and light-sensitive nanostructures, to assist fingerprint techniques (to identify the virus at the contact surface of the gas and solid phase) are also presented.

Green chemistry and coronavirus.

The novel coronavirus pandemic has rapidly spread around the world since December 2019. Various techniques have been applied in identification of SARS-CoV-2 or COVID-19 infection including computed tomography imaging, whole genome sequencing, and molecular methods such as reverse transcription polymerase chain reaction (RT-PCR). This review article discusses the diagnostic methods currently being deployed for the SARS-CoV-2 identification including optical biosensors and point-of-care diagnostics that are on the horizon. These innovative technologies may provide a more accurate, sensitive and rapid diagnosis of SARS-CoV-2 to manage the present novel coronavirus outbreak, and could be beneficial in preventing any future epidemics. Furthermore, the use of green synthesized nanomaterials in the optical biosensor devices could leads to sustainable and environmentally-friendly approaches for addressing this crisis.

COVID-19: Significance of antibodies.

The newly emerged severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has recently caused pandemic Coronavirus Disease-2019 (COVID-19). Considering the serious medical, economic and social consequences of this pandemic and the lack of definite medication and vaccine it is necessary to describe natural immune responses to the SARS-CoV-2 in order to exploit them for treating the patients and monitoring the general population. Moreover, detecting the most immunogenic antigens of the virus is fundamental for designing effective vaccines. Antibodies being valuable for diagnostic therapeutic and protective purposes are suitable to be addressed in this context. Herein, we have summarized the findings of serological investigations and the outcomes of neutralizing antibodies administration in COVID-19 patients.