Glycolytic stress deteriorates 229E virulence to improve host defense response.

Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose (2-DG), a molecule restricting substrate availability, has recently gained attention as a potential antiviral drug. The results revealed that 229E human coronavirus promoted glycolysis, producing a significant increase in the concentration of fluorescent 2-NBDG, a glucose analog, particularly in the infected host cells. The addition of 2-DG decreased its viral replication and suppressed infection-induced cell death and cytopathic effects, thereby improving the antiviral host defense response. It was also observed that administration of low doses of 2-DG inhibited glucose uptake, indicating that 2-DG consumption in virus-infected host cells was mediated by high-affinity glucose transporters, whose levels were amplified upon coronavirus infection. Our findings indicated that 2-DG could be a potential drug to improve the host defense system in coronavirus-infected cells.

Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.

Emerging bio-contaminants such as viruses have affected health and environment settings of every country. Viruses are the minuscule entities resulting in severe contagious diseases like SARS, MERS, Ebola, and avian influenza. Recent epidemic like the SARS-CoV-2, the virus has undergone mutations strengthen them and allowing to escape from the remedies. Comprehensive knowledge of viruses is essential for the development of targeted therapeutic and vaccination treatments. Animal models mimicking human biology like non-human primates, rats, mice, and rabbits offer competitive advantage to assess risk of viral infections, chemical toxins, nanoparticles, and microbes. However, their economic maintenance has always been an issue. Furthermore, the redundancy of experimental results due to aforementioned aspects is also in examine. Hence, exploration for the alternative animal models is crucial for risk assessments. The current review examines zebrafish traits and explores the possibilities to monitor emerging bio-contaminants. Additionally, a comprehensive picture of the bio contaminant and virus particle invasion and abatement mechanisms in zebrafish and human cells is presented. Moreover, a zebrafish model to investigate the emerging viruses such as coronaviridae and poxviridae has been suggested.

An Understanding of Coronavirus and exploring the Molecular Dynamics Simulations to Find Promising Candidates against the Mpro of nCoV to Combat the COVID-19: A Systematic Review

The first infection case of new coronavirus was reported at the end of 2019 and after then, the cases are reported in all nations in a very short period. Further, the regular news of mutations in the virus has made life restricted with appropriate behavior. To date, a new strain (Omicron and its new subvariant Omicron XE) has brought fear amongst us due to a higher trajectory of increase in the number of cases. The researchers thus started giving attention to this viral infection and discovering drug-like candidates to cure the infections. Finding a drug for any viral infection is not an easy task and takes plenty of time. Therefore, computational chemistry/bioinformatics is followed to get promising molecules against viral infection. Molecular dynamics (MD) simulations are being explored to get drug candidates in a short period. The molecules are screened via molecular docking, which provides preliminary information which can be further verified by MD simulations. To understand the change in structure, MD simulations generated several trajectories such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, and radius of gyration for the main protease (Mpro) of the new coronavirus (nCoV) in the presence of small molecules. Additionally, change in free energy for the formation of complex of Mpro of nCoV with the small molecule can be determined by applying molecular mechanics with generalized born and surface area solvation (MM-GBSA). Thus, the promising molecules can be further explored for clinical trials to combat COVID-19. Graphical

Changing Dynamics of SARS-CoV-2: A Global Challenge

Since November 2019, SARS-CoV-2 has been a matter of global concern due to its rapid spread, the millions of deaths it caused, and repeated waves of infections. One after another, many variants of this novel virus have come into existence due to its constant mutability, specifically in the spike glycoprotein region. The tally for variants of concern (VOCs), which already include Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2), has increased to five with the latest appearance of Omicron (B.1.1.529). In our study, we examine the effect of the transmissibility and infectious potential of the virus due to various mutations of SARS-CoV-2, especially in the receptor-binding domain (RBD). We discuss the role of genome sequencing in tracing all the mutations and the importance of the R value (reproductive number) to understand the virus spread. We also review the effectiveness of the available vaccines on the variants of concern, as the rapid spread of the newly emergent Omicron variant has raised doubts about the usefulness of the current vaccines. The use of a mixed vaccination strategy has proved to be effective, yet the newer variants, such as Omicron, demand booster doses for the population. Multivalent immunogens could be considered as the plausible solution for conferring protection against potential new mutants of the virus in the future.

Nonthermal plasma‐generated ozone inhibits human coronavirus 229E infectivity on glass surface

Ozone has been used for surface disinfection to contain bacterial, fungal, mold, and certain viral infections;however, the use of ozone generated from nonthermal plasma devices have not been thoroughly investigated for surface disinfection. Here, we aimed to determine the impact of nonthermal plasma‐generated ozone (PGO) on the coronavirus. Human coronavirus 229E was exposed to PGO and its infectivity was evaluated. PGO exposure of approximately 7 ppm reduced the viral titer after 4 h. Our results indicate that PGO exposure not only reduces the expression of the viral nucleocapsid gene and spike glycoprotein levels but may also stimulate the expression of the antiviral response gene in host cells. These findings can thus be useful to support existing surface disinfection methods. [ FROM AUTHOR] Copyright of Plasma Processes & Polymers is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses.

Role of Dexamethasone and Methylprednisolone Corticosteroids in Coronavirus Disease 2019 Hospitalized Patients: A Review.

The WHO announced coronavirus disease 2019 (COVID-19) as a pandemic disease globally on March 11, 2020, after it emerged in China. The emergence of COVID-19 has lasted over a year, and despite promising vaccine reports that have been produced, we still have a long way to go until such remedies are accessible to everyone. The immunomodulatory strategy has been kept at the top priority for the research agenda for COVID-19. Corticosteroids have been used to modulate the immune response in a wide range of diseases for the last 70 years. These drugs have been shown to avoid and reduce inflammation in tissues and the bloodstream through non-genomic and genomic effects. Now, the use of corticosteroids increased the chance of survival and relief by combating the viral strong inflammatory impacts and has moved to the forefront in the management of patients seeking supplemental oxygen. The goal of this review is to illuminate dexamethasone and methylprednisolone, i.e., in terms of their chemical and physical properties, role in COVID-19 patients suffering from pneumonia, the proposed mode of action in COVID-19, pharmacokinetics, pharmacodynamics, clinical outcomes in immunocompromised populations with COVID-19, interaction with other drugs, and contradiction to explore the trends and perspectives for future research. Literature was searched from scientific databases such as Science Direct, Wiley, Springer, PubMed, and books for the preparation of this review. The RECOVERY trial, a massive, multidisciplinary, randomized, and open-label trial, is mainly accountable for recommendations over the usage of corticosteroids in COVID-19 patients. The corticosteroids such as dexamethasone and methylprednisolone in the form of medication have anti-inflammatory, analgesic, and anti-allergic characteristics, including the ability to inhibit the immune system. These drugs are also recommended for treating symptoms of multiple ailments such as rheumatic and autoimmune diseases, leukemia, multiple myeloma, and Hodgkin's and non-Hodgkin's lymphoma along with other drugs. Toxicology studies proved them safe usually at low dosage via oral or other routes.

The inactivation and destruction of viruses by reactive oxygen species generated through physical and cold atmospheric plasma techniques: Current status and perspectives.

BACKGROUND: Outbreaks of airborne viral infections, such as COVID-19, can cause panic regarding other severe respiratory syndrome diseases that may develop and affect public health. It is therefore necessary to develop control methods that offer protection against such viruses. AIM OF REVIEW: To identify a feasible solution for virus deactivation, we critically reviewed methods of generating reactive oxygen species (ROS), which can attack a wide range of molecular targets to induce antiviral activity, accounting for their flexibility in facilitating host defense mechanisms against a comprehensive range of pathogens. Recently, the role of ROS in microbial decontamination has been critically investigated as a major topic in infectious diseases. ROS can eradicate pathogens directly by inducing oxidative stress or indirectly by promoting pathogen removal through numerous non-oxidative mechanisms, including autophagy, T-cell responses, and pattern recognition receptor signaling. KEY SCIENTIFIC CONCEPTS OF REVIEW: In this article, we reviewed possible methods for the in vitro generation of ROS with antiviral activity. Furthermore, we discuss, in detail, the novel and environmentally friendly cold plasma delivery system in the destruction of viruses. This review highlights the potential of ROS as therapeutic mediators to modernize current techniques and improvement on the efficiency of inactivating SARS-CoV2 and other viruses.

In Silico Evaluation of Binding of 2-Deoxy-D-Glucose with Mpro of nCoV to Combat COVID-19.

COVID-19 has threatened the existence of humanity andthis infection occurs due to SARS-CoV-2 or novel coronavirus, was first reported in Wuhan, China. Therefore, there is a need to find a promising drug to cure the people suffering from the infection. The second wave of this viral infection was shaking the world in the first half of 2021. Drugs Controllers of India has allowed the emergency use of 2-deoxy-D-glucose (2DG) in 2021 for patients suffering from this viral infection. The potentiality of 2-deoxy-D-glucose to intervene in D-glucose metabolism exists and energy deprivation is an effective parameter to inhibit cancer cell development. Once 2DG arrives in the cells, it becomes phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG6P), a charged molecule expressively captured inside the cells. On the other hand, 2DG lacks the ability to convert into fructose-6-phosphate, resulting in a hampering of the activity of both glucose-6-phosphate isomerase and hexokinase, and finally causing cell death. Hence, the potential and effectiveness of 2DG with the main protease (Mpro) of novel coronavirus (nCoV) should be investigated using the molecular docking and molecular dynamics (MD) simulations. The ability of 2DG to inhibit the Mpro of nCoV is compared with 2-deoxyglucose (2DAG), an acyclic molecule, and 2-deoxy-D-ribose (2DR). The binding energy of the molecules with the Mpro of nCoV is calculated using molecular docking and superimposed analysis data is obtained. The binding energy of 2DG, 2DR and 2DAG was -2.40, -2.22 and -2.88 kcal/mol respectively. Although the molecular docking does not provide reliable information, therefore, the binding affinity can be confirmed by molecular dynamics simulations. Various trajectories such as Rg, RMSD, RMSF, and hydrogen bonds are obtained from the molecular dynamics (MD) simulations. 2DG was found to be a better inhibitor than the 2DAG and 2DR based on the results obtained from the MD simulations at 300 K. Furthermore, temperature-dependent MD simulations of the Mpro of nCoV with promising 2DG was performed at 295, 310 and 315 K, and the effective binding with the Mpro of nCoV occurred at 295 K. With the use of DFT calculations, optimized geometry and localization of electron density of the frontier molecular orbitals were calculated.