As the latest identified novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variant of concern (VOC), the influence of Omicron on our globe grows promptly. Compared with the last VOC ...(Delta variant), more mutations were identified, which may address the characteristics of Omicron. Considering these crucial mutations and their implications including an increase in transmissibility, COVID‐19 severity, and reduction of efficacy of currently available diagnostics, vaccines, and therapeutics, Omicron has been classified as one of the VOC. Notably, 15 of these mutations reside in the receptor‐binding domain of spike glycoprotein, which may alter transmissibility, infectivity, neutralizing antibody escape, and vaccine breakthrough cases of COVID‐19. Therefore, our present study characterizes the mutational hotspots of the Omicron variant in comparison with the Delta variant of SARS‐CoV‐2. Furthermore, detailed information was analyzed to characterize the global perspective of Omicron, including transmission dynamic, effect on testing, and immunity, which shall promote the progress of the clinical application and basic research. Collectively, our data suggest that due to continuous variation in the spike glycoprotein sequences, the use of coronavirus‐specific attachment inhibitors may not be the current choice of therapy for emerging SARS‐CoV‐2 VOCs. Hence, we need to proceed with a sense of urgency in this matter.
Highlights
First report of characterization of the novel SARS‐CoV‐2 Omicron (B.1.1.529) Variant of Concern (VOC).
Omicron variant is the most divergent SARS‐CoV‐2 variant characterized as the highest number of amino acid substitutions identified in spike glycoprotein, till date.
These mutations in Omicron may be linked with more transmissibility, robust viral binding affinity, and immune escape.
Coronavirus specific attachment inhibitors may not be the current choice of therapy for SARS‐CoV‐2 Omicron (B.1.1.529).
Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately ...leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; and hence it is not effective in-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP) based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
COVID-19, a respiratory infectious disease, occurs due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Millions of individuals around the world have been impacted by the illness, ...which has gravely threatened human health. The development and active involvement of varied vaccines against the COVID-19 have played a great and relieving role in controlling the life-threatening disease. Both the conventional and advanced vaccine platforms are available now to develop vaccines against COVID-19. Therefore, the present systematic review focuses on the global landscape of the COVID-19 vaccines and their current status. Among COVID-19 vaccines, virus like particles (VLPs), subunit vaccines, DNA, RNA-based vaccines, viral vector-based vaccines, inactivated and live-attenuated vaccines are the major contenders and are currently in various phase of clinical trials. Protein subunit, RNA-based and non-replicating viral vector-based platforms have been used majorly. Nevertheless, inactivated virus vaccine has been utilized clinically around the world. The clinical trials revealed that most of the vaccines have local or systemic effects after vaccination and varied efficacy against SARS-CoV-2 and its variants. However, further studies are necessary to refine the technology to minimize adverse effects and improve the safety and efficacy.
COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2; VLPs: Virus like particles; WHO: World Health Organization; E: Envelope; M: Membrane; S: Spike; N: Nucleocapsid; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; FDA: Food and Drug Administration; LNP: lipid-nanoparticle; AZD1222: ChAdOx1 nCoV-19; BNT162b2: Pfizer-BioNTech mRNA vaccine; mRNA-1273: Moderna vaccine; Ad26.COV2.S: Johnson and Johnson - Janssen's vaccine; Gam-COVID-Vac: Sputnik Vaccine; NVX-CoV2373: Novavax vaccine with Matrix-M™ adjuvant.
It will not be an exaggeration to say that there is a component of Raman spectroscopy in every scientist’s life, of course with different involvement levels. The “Raman-effect” based techniques have ...evolved over a period of time to cater to the needs of all researchers who work in a domain involving materials. Raman microscopy, one such technique, quantitatively displays dynamic variation in materials’ properties by amalgamating spectroscopic information collected by means of spatial, temporal and thermal imaging method. Spatial Raman imaging is one of the most widely used Raman microscopic tools, which enables one to image the Raman mode distribution over the sample and is of immense use, especially in biology and engineering. On the other hand, a Raman image evolution with time can be mapped to know how a Raman mode, and reasons therein, behaves with time. Similarly, a thermal Raman map gives information about the effect of temperature on the material to understand temperature dependent phase changes in a material. Here Raman spectromicroscopic techniques and their application in different aspects related to material science have been discussed to highlight how Raman microscopy can be used in areas where hesitancy is observed due to not much awareness about the potential of Raman-related spectromicroscopic techniques.
•Spike glycoprotein undergoes two conformational states i.e. receptor-inaccessible state and receptor-accessible state upon binding to ACE2.•S1 subunit involved in the attachment to the peptidase ...domain (PD) of the ACE2 receptor via RBD and S2 subunit involved in cell and viral membrane fusion.•SARS-CoV-2 and SARS-CoV RBDs use eight identical interacting residues for attachment to the ACE2 receptor.•Main protease (Mpro) doesn’t share cleavage sites with any human encoded proteases; therefore, it can be one of the best drug targets for combating CoVs.
Recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transpired into pandemic coronavirus disease 2019 (COVID-19). SARS-CoV-2 has been rapidly transmitted across the globe within a short period of time, with more than 106 million cases and 2.3 million deaths. The continuous rise in worldwide cases of COVID-19, transmission dynamics of SARS-CoV-2 including re-infections and enormous case-fatality rates emphasizes the urgent need of potential preventive and therapeutic measures. The development of effective therapeutic and preventive measures relies on understanding the molecular and cellular mechanism of replication exhibited by SARS-CoV-2. The structure of SARS-CoV-2 is ranging from 90–120 nm that comprises surface viral proteins including spike, envelope, membrane which are attached in host lipid bilayer containing the helical nucleocapsid comprising viral RNA. Spike (S) glycoprotein initiates the attachment of SARS-CoV-2 with a widely expressed cellular receptor angiotensin-converting enzyme 2 (ACE2), and subsequent S glycoprotein priming via serine protease TMPRSS2. Prominently, comprehensive analysis of structural insights into the crucial SARS-CoV-2 proteins may lead us to design effective therapeutics molecules. The present article, emphasizes the molecular and structural perspective of SARS-CoV-2 including mechanistic insights in its replication.
The recent outbreak of COVID-19 caused by SARS-CoV-2 brought a great global public health and economic concern. SARS-CoV-2 is an enveloped RNA virus, from the genus
Betacoronavirus.
Although few ...molecules have been tested and shown some efficacy against SARS-CoV-2 in humans but a safe and cost-effective attachment inhibitors are still required for the treatment of COVID-19. Natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Therefore, this study was planned to screen natural products from Ayurveda that have the potential to modulate host immune system as well as block the virus entry in host cells by interfering its interaction with cellular receptor and may be used to develop an effective and broad-spectrum strategy for the management of COVID-19 as well as other coronavirus infections in coming future. To decipher the antiviral activity of the selected natural products, molecular docking was performed. Further, the drug-likeness, pharmacokinetics and toxicity parameters of the selected natural products were determined. Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein (MolDock score − 141.36 and − 148.621 kcal/mole) and ACE2 receptor (MolDock score − 142.647 and − 140.108 kcal/mole) as compared with other selected natural products/drugs and controls. Also, the pharmacokinetics data illustrated that all selected natural products have better pharmacological properties (low molecular weight; no violation of Lipinski rule of five, good absorption profiles, oral bioavailability, good blood–brain barrier penetration, and low toxicity risk). Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells. However, few other natural products like resveratrol, quercetin, luteolin, naringenin, zingiberene, and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2.
The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for ...receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.
This book focuses on various aspects and applications of drug repurposing, the understanding of which is important for treating diseases. Due to the high costs and time associated with the new drug ...discovery process, the inclination toward drug repurposing is increasing for common as well as rare diseases. A major focus of this book is understanding the role of drug repurposing to develop drugs for infectious diseases, including antivirals, antibacterial and anticancer drugs, as well as immunotherapeutics.
SARS-CoV-2, the causative agent of COVID-19, has imposed a major public health threat, which needs effective therapeutics and vaccination strategies. Several potential candidate vaccines being ...rapidly developed are in clinical evaluation. Considering the crucial role of SARS-CoV-2 spike (S) glycoprotein in virus attachment, entry, and induction of neutralizing antibodies, S protein is being widely used as a target for vaccine development. Based on advances in techniques for vaccine design, inactivated, live-vectored, nucleic acid, and recombinant COVID-19 vaccines are being developed and tested for their efficacy. Phase3 clinical trials are underway or will soon begin for several of these vaccines. Assuming that clinical efficacy is shown for one or more vaccines, safety is a major aspect to be considered before deploying such vaccines to the public. The current review focuses on the recent advances in recombinant COVID-19 vaccine research and development and associated issues.
Strain control of Urbach energy in Cr-doped PrFeO3 Kumar, Anil; Warshi, M. Kamal; Mishra, Vikash ...
Applied physics. A, Materials science & processing,
09/2017, Letnik:
123, Številka:
9
Journal Article
Recenzirano
Polycrystalline samples of PrFe
1−
x
Cr
x
O
3
having average particle size of ~90 nm have been prepared by wet chemical route. The structural phase purity of the prepared samples is confirmed by ...powder X-ray diffraction followed by Rietveld refinements. It is observed that with Cr doping, the Urbach energy (
E
u
) increases. The
E
u
is measure of the various disorders present in the sample, such as chemical and structural. To understand the contribution to the
E
u
due to chemical and structural disorders, we have probed the chemical and structural disorders in the samples by elemental mappings and through X-ray diffraction experiments, respectively. Elemental mapping confirms chemical homogeneity of prepared samples. It is observed that with Cr doping the crystallographic strain increases and Urbach energy shows the similar scaling.
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