Selinexor and COVID-19: The Neglected Warden.

A novel severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) has been confirmed as the cause of the global pandemic coronavirus disease 2019 (COVID-19). Different repurposed drugs have been trialed and used in the management of COVID-19. One of these agents was the anti-cancer Selinexor (SXR). SXR is an anti-cancer drug that acts by inhibition of nuclear exportin-1 (XPO1), which inhibits transport of nuclear proteins from the nucleus to the cytoplasm, leading to the induction of cell-cycle arrest and apoptosis. XPO1 inhibitors had antiviral effects, mainly against respiratory syncytial virus (RSV) and influenza virus. SXR inhibits transport of SARS-CoV-2 nuclear proteins to the cytoplasm with further inhibition of SARS-CoV-2 proliferation. SXR has the ability to prevent the development of a cytokine storm in COVID-19 by inhibiting the release of pro-inflammatory cytokines with the augmentation release of anti-inflammatory cytokines. In conclusion, SARS-CoV-2 infection is linked with activation of XPO1, leading to the triggering of inflammatory reactions and oxidative stress. Inhibition of XPO1 by Selinexor (SXR), a selective inhibitor of nuclear export (SINE), can reduce the proliferation of SARS-CoV-2 and associated inflammatory disorders. Preclinical and clinical studies are warranted in this regard.

Combination of RT-LAMP and fluorescence spectroscopy using chemometric techniques for an ultra-sensitive and rapid alternative for the detection of SARS-CoV-2.

The increased spread of COVID-19 caused by SARS-CoV-2 has made it necessary to develop more efficient, fast, accurate, specific, sensitive and easy-to-use detection platforms to overcome the disadvantages of gold standard methods (RT-qPCR). Here an approach was developed for the detection of the SARS-CoV-2 virus using the loop-mediated isothermal amplification (LAMP) technique for SARS-CoV-2 RNA target amplification in samples of nasopharyngeal swabs. The discrimination between positive and negative SARS-CoV-2 samples was achieved by using fluorescence spectra generated by the excitation of the LAMP's DNA intercalator dye at λ497 nm in a fluorescence spectrophotometer and chemometric tools. Exploratory analysis of the 83 sample spectra using principal component analysis (PCA) indicated a trend in differentiation between positive and negative samples resulting from the peak emission of the fluorescent dye. The classification was performed by partial least squares discriminant analysis (PLS-DA) achieving a sensitivity, a specificity and an accuracy of 100%, 95% and 89%, respectively for the discrimination between negative and positive samples from 1.58 to 0.25 ng L-1 after LAMP amplification. Therefore, this study indicates that the use of the LAMP technique in fluorescence spectroscopy may offer a fast (<1 hour), sensitive and low-cost method.

Essential oils block cellular entry of SARS-CoV-2 delta variant.

Aiming to fill a gap in the literature, we aimed to identify the most promising EOs blocking in vitro cellular entry of SARS-CoV-2 delta variant without conferring human cytotoxicity and provide insights into the influence of their composition on these activities. Twelve EOs were characterized by gas chromatography coupled to mass spectrometry. The antiviral and cytotoxicity activities were determined using the cell-based pseudoviral entry with SARS-CoV-2 delta pseudovirus and the XTT assay in HeLa cells expressing human angiotensin-converting enzyme 2 (HeLa ACE-2), respectively. Syzygium aromaticum, Cymbopogon citratus, Citrus limon, Pelargonium graveolens, Origanum vulgare, "Illicium verum", and Matricaria recutita showed EC50 lowered or close to 1 µg/mL but also the lowest CC50 (0.20-1.70 µg/mL), except "I. verum" (30.00 µg/mL). Among these, "I. verum", C. limon, P. graveolens and S. aromaticum proved to be promising alternatives for SARS-CoV-2 delta variant inhibition (therapeutic index above 4), which possibly was related to the compounds (E)-anetole, limonene and beta-pinene, citronellol, and eugenol, respectively.

Development and Application of an SPR Nanobiosensor Based on AuNPs for the Detection of SARS-CoV-2 on Food Surfaces.

A new transmission route of SARS-CoV-2 through food was recently considered by the World Health Organization (WHO), and, given the pandemic scenario, the search for fast, sensitive, and low-cost methods is necessary. Biosensors have become a viable alternative for large-scale testing because they overcome the limitations of standard techniques. Herein, we investigated the ability of gold spherical nanoparticles (AuNPs) functionalized with oligonucleotides to detect SARS-CoV-2 and demonstrated their potential to be used as plasmonic nanobiosensors. The loop-mediated isothermal amplification (LAMP) technique was used to amplify the viral genetic material from the raw virus-containing solution without any preparation. The detection of virus presence or absence was performed by ultraviolet-visible (UV-Vis) absorption spectroscopy, by monitoring the absorption band of the surface plasmonic resonance (SPR) of the AuNPs. The displacement of the peak by 525 nm from the functionalized AuNPs indicated the absence of the virus (particular region of gold). On the other hand, the region ~300 nm indicated the presence of the virus when RNA bound to the functionalized AuNPs. The nanobiosensor system was designed to detect a region of the N gene in a dynamic concentration range from 0.1 to 50 × 103 ng·mL-1 with a limit of detection (LOD) of 1 ng·mL-1 (2.7 × 103 copy per µL), indicating excellent sensitivity. The nanobiosensor was applied to detect the SARS-CoV-2 virus on the surfaces of vegetables and showed 100% accuracy compared to the standard quantitative reverse transcription polymerase chain reaction (RT-qPCR) technique. Therefore, the nanobiosensor is sensitive, selective, and simple, providing a viable alternative for the rapid detection of SARS-CoV-2 in ready-to-eat vegetables.

A Computational Approach to Elucidate the Interactions of Chemicals From Artemisia annua Targeted Toward SARS-CoV-2 Main Protease Inhibition for COVID-19 Treatment.

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses, including the coronavirus, is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2 that is currently ravaging the world. It is therefore necessary to evaluate individual chemicals of the plant for inhibitory potential against SARS-CoV-2 for the purpose of designing drugs for the treatment of COVID-19. In this study, we employed computational techniques comprising molecular docking, binding free energy calculations, pharmacophore modeling, induced-fit docking, molecular dynamics simulation, and ADMET predictions to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, isokaempferide, kaempferol, quercimeritrin, apigenin, penduletin, isoquercitrin, astragalin, luteolin-7-glucoside, and isorhamnetin were ranked the highest, with docking scores ranging from -7.84 to -7.15 kcal/mol compared with the -6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide, and kaempferol, like the standard ligand, interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. Rhamnocitrin demonstrated good stability in the active site of the protein as there were no significant conformational changes during the simulation process. These compounds also possess acceptable druglike properties and a good safety profile. Hence, they could be considered for experimental studies and further development of drugs against COVID-19.

A systematic review of the advancement on colorimetric nanobiosensors for SARS-CoV-2 detection.

The current pandemic of the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) killed about 6.4 million and infected more than 600 million individuals by august of 2022, and researchers worldwide are searching for fast and selective approaches for this virus detection. Colorimetric biosensors are an excellent alternative because they are sensitive, simple, fast, and low-cost for rapid detection of SARS-CoV-2 compared to standard Enzyme-linked immunosorbent assay (ELISA) and Polymerase Chain Reaction (PCR) techniques. This study systematically searched and reviewed literature data related to colorimetric biosensors in detecting SARS-CoV-2 viruses, recovered from the Scopus (n = 16), Web of Science (n = 19), PubMed (n = 19), and Science Direct (n = 17) databases totalizing n = 71 articles. Data were analyzed for the type of nanomaterial, biorecognition material at the detection limit (LOD), and devices designed for diagnostics. The most applied nanomaterial were gold nanoparticles, in their original form and hybrid in quantum dots and core-shell. In addition, we show high specificity in point-of-care (POC) diagnostic devices as a faster and cheaper alternative for clinical diagnosis. Finally, the highlights of the colorimetric biosensor developed for diagnostic devices applied in swabs, surgical masks, and lateral flow immunoassays were presented.

A systematic review of the advancement on colorimetric nanobiosensors for SARS-CoV-2 detection

The current pandemic of the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) killed about 6.4 million and infected more than 600 million individuals by august of 2022, and researchers worldwide are searching for fast and selective approaches for this virus detection. Colorimetric biosensors are an excellent alternative because they are sensitive, simple, fast, and low-cost for rapid detection of SARS-CoV-2 compared to standard Enzyme-linked immunosorbent assay (ELISA) and Polymerase Chain Reaction (PCR) techniques. This study systematically searched and reviewed literature data related to colorimetric biosensors in detecting SARS-CoV-2 viruses, recovered from the Scopus (n=16), Web of Science (n=19), PubMed (n=19), and Science Direct (n=17) databases totalizing n=71 articles. Data were analyzed for the type of nanomaterial, biorecognition material at the detection limit (LOD), and devices designed for diagnostics. The most applied nanomaterial were gold nanoparticles, in their original form and hybrid in quantum dots and core-shell. In addition, we show high specificity in point-of-care (POC) diagnostic devices as a faster and cheaper alternative for clinical diagnosis. Finally, the highlights of the colorimetric biosensor developed for diagnostic devices applied in swabs, surgical masks, and lateral flow immunoassays were presented. Graphical

Mucormycosis in the COVID-19 Environment: A Multifaceted Complication.

The second wave of coronavirus disease 2019 (COVID-19) caused severe infections with high mortality. An increase in the cases of COVID-19-associated mucormycosis (CAM) was reported predominantly in India. Commonly present in immunocompromised individuals, mucormycosis is often a life-threatening condition. Confounding factors and molecular mechanisms associated with CAM are still not well understood, and there is a need for careful research in this direction. In this review, a brief account of the diagnosis, management, and advancement in drug discovery for mucormycosis has been provided. Here, we summarize major factors that dictate the occurrence of mucormycosis in COVID-19 patients through the analysis of published literature and case reports. Major predisposing factors to mucormycosis appear to be uncontrolled diabetes, steroid therapy, and certain cancers. At the molecular level, increased levels of iron in COVID-19 might contribute to mucormycosis. We have also discussed the potential role and regulation of iron metabolism in COVID-19 patients in establishing fungal growth. Other factors including diabetes prevalence and fungal spore burden in India as contributing factors have also been discussed.

ATR-FTIR spectroscopy and chemometrics as a quick and simple alternative for discrimination of SARS-CoV-2 infected food of animal origin.

Alternative routes such as virus transmission or cross-contamination by food have been suggested, due to reported cases of SARS-CoV-2 in frozen chicken wings and fish or seafood. Delay in routine testing due to the dependence on the PCR technique as the standard method leads to greater virus dissemination. Therefore, alternative detection methods such as FTIR spectroscopy emerge as an option. Here, we demonstrate a fast (3 min), simple and reagent-free methodology using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy for discrimination of food (chicken, beef and fish) contaminated with the SARS-CoV-2 virus. From the IR spectra of the samples, the "bio-fingerprint" (800 - 1900 cm-1) was selected to investigate the distinctions caused by the virus contamination. Exploratory analysis of the spectra, using Principal Component of Analysis (PCA), indicated the differentiation in the data due to the presence of single bands, marked as contamination from nucleic acids including viral RNA. Furthermore, the partial least squares discriminant analysis (PLS-DA) classification model allowed for discrimination of each matrix in its pure form and its contaminated counterpart with sensitivity, specificity and accuracy of 100 %. Therefore, this study indicates that the use of ATR-FTIR can offer a fast and low cost and not require chemical reagents and with minimal sample preparation to detect the SARS-CoV-2 virus in food matrices, ensuring food safety and non-dissemination by consumers.

Mucormycosis in the COVID-19 Environment: A Multifaceted Complication

The second wave of coronavirus disease 2019 (COVID-19) caused severe infections with high mortality. An increase in the cases of COVID-19-associated mucormycosis (CAM) was reported predominantly in India. Commonly present in immunocompromised individuals, mucormycosis is often a life-threatening condition. Confounding factors and molecular mechanisms associated with CAM are still not well understood, and there is a need for careful research in this direction. In this review, a brief account of the diagnosis, management, and advancement in drug discovery for mucormycosis has been provided. Here, we summarize major factors that dictate the occurrence of mucormycosis in COVID-19 patients through the analysis of published literature and case reports. Major predisposing factors to mucormycosis appear to be uncontrolled diabetes, steroid therapy, and certain cancers. At the molecular level, increased levels of iron in COVID-19 might contribute to mucormycosis. We have also discussed the potential role and regulation of iron metabolism in COVID-19 patients in establishing fungal growth. Other factors including diabetes prevalence and fungal spore burden in India as contributing factors have also been discussed.

A Computational Approach to Elucidate the Interactions of Chemicals From Artemisia annua Targeted Toward SARS-CoV-2 Main Protease Inhibition for COVID-19 Treatment

The inhibitory potential of Artemisia annua, a well-known antimalarial herb, against several viruses, including the coronavirus, is increasingly gaining recognition. The plant extract has shown significant activity against both the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the novel SARS-CoV-2 that is currently ravaging the world. It is therefore necessary to evaluate individual chemicals of the plant for inhibitory potential against SARS-CoV-2 for the purpose of designing drugs for the treatment of COVID-19. In this study, we employed computational techniques comprising molecular docking, binding free energy calculations, pharmacophore modeling, induced-fit docking, molecular dynamics simulation, and ADMET predictions to identify potential inhibitors of the SARS-CoV-2 main protease (Mpro) from 168 bioactive compounds of Artemisia annua. Rhamnocitrin, isokaempferide, kaempferol, quercimeritrin, apigenin, penduletin, isoquercitrin, astragalin, luteolin-7-glucoside, and isorhamnetin were ranked the highest, with docking scores ranging from −7.84 to −7.15 kcal/mol compared with the −6.59 kcal/mol demonstrated by the standard ligand. Rhamnocitrin, Isokaempferide, and kaempferol, like the standard ligand, interacted with important active site amino acid residues like HIS 41, CYS 145, ASN 142, and GLU 166, among others. Rhamnocitrin demonstrated good stability in the active site of the protein as there were no significant conformational changes during the simulation process. These compounds also possess acceptable druglike properties and a good safety profile. Hence, they could be considered for experimental studies and further development of drugs against COVID-19.

COVID-19 contamination through food: A study with Brazilian consumers of different socioeconomic and demographic characteristics.

This study aimed to investigate through free word association the perception of Brazilian consumers regarding the possibility of infection with the SARS-CoV-2 virus through food. One thousand individuals answered the questionnaire via an online platform. Most cited terms (hygiene-8%, fear-8%, caution-5%) and categories (negative attitudes and feeling-72% and sanitization-60%) were related to overall COVID-19 infection rather than their specific infection through the food. The perception of the possibility of risk of this type of cross-contamination was greater for male participants, within the food field, with high income (>10 minimum wages), and from the midwest region. Nonetheless, there are still doubts regarding this possibility, especially for participants with low income (≤10 minimum wages), females, higher education (≥secondary school), who exercise professional activity outside the food sector and from most regions of Brazil. Practical applications: Although the SARS-CoV-2 virus was discovered 2 years ago, the emergence of new variants such as Omicron has increased infection and mortality rates worldwide. A possible way of COVID-19 infection is cross-contamination through food handling and contact surfaces if preventive measures are not applied. In this context, understanding the consumer perception from a continental-size country such as Brazil, with a wide variety of socioeconomic profiles, is crucial to minimize the severe impacts of the pandemic. Our study demonstrates the need to disseminate scientific information in different media to reduce misinformation, especially social media because most Brazilian consumers had doubts and uncertainties about the possibility of COVID-19 infection from cross-contamination through food.

Updating the use of nano-biosensors as promising devices for the diagnosis of coronavirus family members: A systematic review.

Coronavidae viruses, such as SARS-CoV, SARS-CoV-2, and MERS-CoV, cause severe lower respiratory tract infection, acute respiratory distress syndrome and extrapulmonary manifestations, such as diarrhea and fever, eventually leading to death. Fast, accurate, reproductible, and cost-effective SARS-CoV-2 identification can be achieved employing nano-biosensors, reinforcing conventional methodologies to avoid the spread of COVID-19 within and across communities. Nano-biosensors built using gold, silver, graphene, In2O3 nanowire and iron oxide nanoparticles, Quantum Dots and carbon nanofibers have been successfully employed to detect specific virus antigens - nucleic acid sequences and/or proteins -or host antibodies produced in response to viral infection. Biorecognition counterpart molecules have been immobilized on the surface of these nanomaterials, leading to selective virus detection by optical or electrochemical transducer systems. This systematic review assessed studies on described and tested immunonsensors and genosensors designed from distinct nanomaterials available at the Pubmed, Scopus, and Science Direct databases. Twenty-three nano biosensors were found suitable for unequivocal coronavirus detection in clinical samples. Nano-biosensors coupled to RT-LAMP/RT-PCR assays can optimize RNA extraction, reduce analysis times and/or eliminate sophisticated instrumentation. Although promising for the diagnosis of Coronavidae family members, further trials in large populations must be adequately and rigorously conducted to address nano-biosensor applicability in the clinical practice for early coronavirus infection detection.

An Evaluation of the Potential of Essential Oils against SARS-CoV-2 from In Silico Studies through the Systematic Review Using a Chemometric Approach.

Essential oils (EOs) and their compounds have attracted particular attention for their reported beneficial properties, especially their antiviral potential. However, data regarding their anti-SARS-CoV-2 potential are scarce in the literature. Thus, this study aimed to identify the most promising EO compounds against SARS-CoV-2 based on their physicochemical, pharmacokinetic, and toxicity properties. A systematic literature search retrieved 1669 articles; 40 met the eligibility criteria, and 35 were eligible for analysis. These studies resulted in 465 EO compounds evaluated against 11 human and/or SARS-CoV-2 target proteins. Ninety-four EO compounds and seven reference drugs were clustered by the highest predicted binding affinity. Furthermore, 41 EO compounds showed suitable drug-likeness and bioactivity score indices (≥0.67). Among these EO compounds, 15 were considered the most promising against SARS-CoV-2 with the ADME/T index ranging from 0.86 to 0.81. Some plant species were identified as EO potential sources with anti-SARS-CoV-2 activity, such as Melissa officinalis Arcang, Zataria multiflora Boiss, Eugenia brasiliensis Cambess, Zingiber zerumbet Triboun & K.Larsen, Cedrus libani A.Rich, and Vetiveria zizanoides Nash. Our work can help fill the gap in the literature and guide further in vitro and in vivo studies, intending to optimize the finding of effective EOs against COVID-19.

The Spread of the COVID-19 Outbreak in Brazil: An Overview by Kohonen Self-Organizing Map Networks.

Background and objective: In the current pandemic scenario, data mining tools are fundamental to evaluate the measures adopted to contain the spread of COVID-19. In this study, unsupervised neural networks of the Self-Organizing Maps (SOM) type were used to assess the spatial and temporal spread of COVID-19 in Brazil, according to the number of cases and deaths in regions, states, and cities. Materials and methods: The SOM applied in this context does not evaluate which measures applied have helped contain the spread of the disease, but these datasets represent the repercussions of the country's measures, which were implemented to contain the virus' spread. Results: This approach demonstrated that the spread of the disease in Brazil does not have a standard behavior, changing according to the region, state, or city. The analyses showed that cities and states in the north and northeast regions of the country were the most affected by the disease, with the highest number of cases and deaths registered per 100,000 inhabitants. Conclusions: The SOM clustering was able to spatially group cities, states, and regions according to their coronavirus cases, with similar behavior. Thus, it is possible to benefit from the use of similar strategies to deal with the virus' spread in these cities, states, and regions.