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1.
Nieren- und Hochdruckkrankheiten ; 52(4):134-135, 2023.
Article in English | EMBASE | ID: covidwho-20241899

ABSTRACT

Objective: COVID-19 has emerged as a significant global health crisis causing devastating effects on world population accounting for over 6 million deaths worldwide. Although acute RTI is the prevalent cause of morbidity, kidney outcomes centered on a spectrum of AKI have evolved over the course of the pandemic. Especially the emerging variants have posed a daunting challenge to the scientific communities, prompting an urging requirement for global contributions in understanding the viral dynamics. In addition to canonical genes, several subgroup- specific accessory genes are located between the S and E genes of coronaviruses regarding which little is known. Previous studies have shown that accessory proteins (aps) in viruses function as viroporins that regulate viral infection, propagation and egress [1]. In this study we attempted to characterize the function of aps of coronavirus variants as ion channels. Furthermore, we also probed the interaction of ap4 with the host system. Method(s): Serial passaging (selection pressure), growth kinetics, confocal imaging, genome sequence analysis and proteomics were performed in Huh-7, MRC5 cells and/or human monocyte derived macrophages. Potassium uptake assay was performed in a Saccharo myces cerevisiae strain, which lacks the potassium transporters trk1 and trk2. Ion conductivity experiments were performed in Xenopus laevis oocytes using Two Electrode Voltage Clamp (TEVC) method. Result(s): Serial passaging demonstrated the acquisition of several frameshift mutations in ORF4 resulting in C-terminally truncated protein versions (ap4 and ap4a) and indicate a strong selection pressure against retaining a complete ORF4 in vitro. Growth kinetics in primary cells illustrated a reduction of viral titers when the full-length ap4 was expressed compared to the C-terminally truncated protein ap4a. Confocal imaging showed that ap4 and ap4a are not exclusively located in a single cellular compartment. Potassium uptake assay in yeast and TEVC analyses in Xenopus oocytes showed that ap4 and ap4a act as a weak K+ selective ion channel. In addition, accessory proteins of other virus variants also elicited microampere range of currents. Conclusion(s): Our study provides the first evidence that ap4 and other accessory proteins of coronavirus variants act as viroporins. Future studies are aimed at demonstrating the role of ap4 during the viral life cycle by modulating ion homeostasis of host cell in vivo (interacting proteins obtained from proteomic studies) and thereby serve as a tool for potential drug target.

2.
Drug Delivery Letters ; 13(2):83-91, 2023.
Article in English | EMBASE | ID: covidwho-20236526

ABSTRACT

Coronavirus disease (COVID-19) is an infectious disease caused by coronavirus. Devel-oping specific drugs for inhibiting replication and viral entry is crucial. Several clinical trial studies are underway to evaluate the efficacy of anti-viral drugs for COVID-19 patients. Nanomedicine formulations can present a novel strategy for targeting the virus life cycle. Nano-drug delivery systems can modify the pharmacodynamics and pharmacokinetics properties of anti-viral drugs and reduce their adverse effects. Moreover, nanocarriers can directly exhibit anti-viral effects. A number of nanocarriers have been studied for this purpose, including liposomes, dendrimers, exosomes and decoy nanoparticles (NPs). Among them, decoy NPs have been considered more as nanodecoys can efficiently protect host cells from the infection of SARS-CoV-2. The aim of this review article is to highlight the probable nanomedicine therapeutic strategies to develop anti-viral drug delivery systems for the treatment of COVID-19.Copyright © 2023 Bentham Science Publishers.

3.
Anales de la Facultad de Medicina ; 84(1):55-62, 2023.
Article in English | EMBASE | ID: covidwho-20235816

ABSTRACT

Introduction: Currently, isolated from SARS-CoV-2 virus exceed 600 million cases in the world. Objective(s): Isolation and characterization of the SARS-CoV-2 virus causing COVID-19 at the beginning of the pandemic in Peru. Method(s): Twenty nasal and pharyngeal swab samples were isolated from SARS-CoV-2 using two cell lines, Vero ATCC CCL-81 and Vero E-6;virus identification was performed by RT-PCR and the onset of cytopathic effect (CPE) was evaluated by indirect immunofluorescence and subsequent identification by genomic sequencing. One of the most widely circulating isolates were selected and named the prototype strain (PE/B.1.1/28549/2020). Then 10 successive passages were performed on Vero ATCC CCL-81 cells to assess mutation dynamics. Result(s): Results detected 11 virus isolates by cytopathic effect, and subsequently confirmed by RT-PCR and indirect immunofluorescence. Of these, six were sequenced and identified as the lineages B.1, B.1.1, B.1.1.1, and B.1.205 according to the Pango lineage nomenclature. The prototype strain corresponded to lineage B.1.1. The analysis of the strains from the successive passages showed mutations mainly at in the spike (S) protein of the virus without variation in the identity of the lineage. Conclusion(s): Four lineages were isolated in the Vero ATCC CCL-81 cell line. Subcultures in the same cell line showed mutations in the spike protein indicating greater adaptability to the host cell and variation in pathogenicity in vitro, a behavior that allows it to have more survival success.Copyright © 2023 Anales de la Facultad de Medicina. All rights reserved.

4.
Comput Methods Programs Biomed ; 238: 107622, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2327992

ABSTRACT

BACKGROUND AND OBJECTIVE: Respiratory diseases caused by viruses are a major human health problem. To better control the infection and understand the pathogenesis of these diseases, this paper studied SARS-CoV-2, a novel coronavirus outbreak, as an example. METHODS: Based on coupled computational fluid and particle dynamics (CFPD) and host-cell dynamics (HCD) analyses, we studied the viral dynamics in the mucus layer of the human nasal cavity-nasopharynx. To reproduce the effect of mucociliary movement on the diffusive and convective transport of viruses in the mucus layer, a 3D-shell model was constructed using CT data of the upper respiratory tract (URT) of volunteers. Considering the mucus environment, the HCD model was established by coupling the target cell-limited model with the convection-diffusion term. Parameter optimization of the HCD model is the key problem in the simulation. Therefore, this study focused on the parameter optimization of the viral dynamics model, divided the geometric model into multiple compartments, and used Monolix to perform the nonlinear mixed effects (NLME) of pharmacometrics to discuss the influence of factors such as the number of mucus layers, number of compartments, diffusion rate, and mucus flow velocity on the prediction results. RESULTS: The findings showed that sufficient experimental data can be used to estimate the corresponding parameters of the HCD model. The optimized convection-diffusion case with a two-layer multi-compartment low-velocity model could accurately predict the viral dynamics. CONCLUSIONS: Its visualization process could explain the symptoms of the disease in the nose and contribute to the prevention and targeted treatment of respiratory diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Nasal Cavity/diagnostic imaging , Nasopharynx , Mucus
5.
Journal of Biological Chemistry ; 299(3 Supplement):S449, 2023.
Article in English | EMBASE | ID: covidwho-2319531

ABSTRACT

Lipid enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Lipid-enveloped viruses include dangerous pathogens such as coronaviruses (SARSCoV-2, etc.), filoviruses (Ebola virus and Marburg virus) and paramyxoviruses (Nipah virus, Hendra virus, etc.). Despite understanding some of the basics of how these viruses cause disease and enter host cells, not much is known on how these dangerous pathogens interact with host cell lipids to achieve new virion formation. The viral matrix or membrane protein regulates assembly and budding from the host cell membrane, connecting the viral lipid envelope to the viral nucleocapsid. Depending on the virus family, this assembly and budding may occur at the plasma membrane or the ER-Golgi intermediate compartment. This presentation will detail the biophysical and biochemical basis of how these emerging pathogens hijack host lipid membrane and metabolic networks to form new virus particles that undergo release from the host cell. These studies were funded in part by the National Institute of Allergy and Infectious Diseases (R01AI081077, AI158220, AI169896).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

6.
Journal of Biological Chemistry ; 299(3 Supplement):S608, 2023.
Article in English | EMBASE | ID: covidwho-2316061

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) targets mainly the respiratory tract. In addition to respiratory symptoms, many extrapulmonary manifestations were observed in the gastrointestinal tract and reported by SARS-CoV-2 patients, including abdominal pain, nausea, and diarrhea. SARS-CoV-2 binds initially to angiotensin-converting enzyme 2 (ACE2) on the host cell surface via its spike (S) protein before it undergoes endocytosis and fusion with the lysosomal membrane. The spike protein of SARS-CoV-2 is a heavily N- and O-glycosylated trimer. Glycosylation is an essential posttranslational modification in the life cycle of membrane and secretory proteins that affects their structural and functional characteristics as well as their trafficking and sorting patterns. This study aimed at elucidating the impact of glycosylation modulation on the trafficking of both S1 subunit and ACE2 as well as their interaction at the cell surface of intestinal epithelial cells. For this purpose, the S1 protein was expressed in COS-1 cells and its glycosylation modified using N-butyldeoxynojirimycin (NB-DNJ), an inhibitor of ER-located alpha-glucosidases I and II, and or 1-deoxymannojirimycin (dMM), an inhibitor of the Golgi-located alpha-mannosidase I. The intracellular and secreted S1 proteins were analyzed by endoglycosidase H treatment. Similarly, ACE2 trafficking to the brush border membrane of intestinal Caco-2 cells was also assessed in the presence or absence of the inhibitors. Finally, the interaction between the S1 protein and ACE2 was investigated at the surface of Caco-2 cells by co-immunoprecipitation. Our data show that NB-DNJ significantly reduced the secretion of S1 proteins in COS-1 cells, while dMM affected S1 secretion to a lesser extent. Moreover, NB-DNJ and dMM differentially affected ACE2 trafficking and sorting to the brush border membrane of intestinal Caco-2 cells. Strikingly, the interaction between S1 and ACE2 was significantly reduced when both proteins were processed by the glycosylation inhibitors, rendering glycosylation and its inhibitors potential candidates for SARS-CoV-2 treatment. This work has been supported by a grant from the German Research Foundation (DFG) grant NA331/15-1 to HYN. M.K. was supported by a scholarship from the Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine (HGNI) and by the DFG grant NA331/15-1.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

7.
Nano Biomedicine and Engineering ; 14(4):343-348, 2022.
Article in English | EMBASE | ID: covidwho-2290867

ABSTRACT

SARS-CoV-2 is a highly pathogenic novel ongoing-pandemic virus. It causes COVID-19. Little is known about SARS-CoV-2 biology, countermeasure, and its origin. SARS-CoV-2 is characterized by high infectiousness and sever pathogenesis. COVID-19 crosses the bounders of all continents in a high spreading manner. Here, several aspects regarding the origin and the molecular structure of this novel virus as well as the production of effective vaccines have been addressed. This article illustrated that SARS-CoV-2 was not being recombined inside laboratory and it has a complicated genome that led to sophisticated pathogenesis. Additionally, an important structural protein known as spike S was demonstrated by researchers as an important protein used by the virus for host cell entry as well as for vaccine development. However, the efforts for viral diagnosis and genomic demonstration as well as vaccine production are promising to tackle COVID-19. These perspectives will help in COVID-19 control. However, further investigations are urgently needed to figure out which controlling tactic is more efficient not only in the case of SARS-CoV-2 but also for future pandemics.Copyright © Mohammed Hamzah Abdulkadhim Al-Saadi and Wisam Hindawi Hoidy.

8.
Chinese Journal of Clinical Infectious Diseases ; 14(2):91-96, 2021.
Article in Chinese | EMBASE | ID: covidwho-2306155

ABSTRACT

During the treatment of critically ill COVID-19 patients it has been revealed that the neutralizing monoclonal antibodies against 2019-nCoV have the advantages of high specificity, high purity, and can be prepared in a large scale, which are expected to be a effective preparation for clinical use. This article introduces the way of 2019-nCoV invasion into the host cells, the major variants of novel coronavirus, and the mechanism of action of anti-2019-nCoV monoclonal antibodies, as well as the progress of research and development of their preparation in major pharmaceutical companies, to provide reference for scientific research and clinical application.Copyright © Chinese Journal of Clinical Infectious Diseases.All rights reserved.

9.
Journal of the Liaquat University of Medical and Health Sciences ; 22(1):3-8, 2023.
Article in English | Scopus | ID: covidwho-2300656

ABSTRACT

The increase in human monkeypox virus (hMPXV) cases amidst the COVID-19 pandemic has raised fear among the general public. The monkeypox virus and the now-extinct smallpox virus belong to the orthopox family of viruses. Although first discovered in 1958, Monkeypox was only well recognized outside the sub-Saharan African countries until the world experienced a monkeypox pandemic in May 2022. The virus is common in some areas of Africa and is often spread through close contact with an infected person or animal. However, recent international trade, travel, and tourism developments have caused viral outbreaks outside Africa. The most recent pandemic in 2022 has been strange because epidemiologists have not found a link between cases and the virus's ability to spread through sexual contact. The structural and pathogenic activities of the virus that attack host cells need to be better understood. Because of this, it is important to know how viruses and the immune system work together to develop effective ways to treat and prevent diseases. To summarize existing research on Monkeypox, we conducted a narrative review using the MEDLINE, EMBASE, PUBMED, and Scopus databases to look at simultaneous zoonotic pandemics caused by the SARS-CoV-2 or COVID-19 coronavirus and presented the most to date information on the symptoms, epidemiology, diagnosis, prevention, and treatment of Monkeypox. However, more research on epidemiological details, ecology, and virus biology in endemic areas is required to understand the virus better and prevent further human infection. This short review discusses the research results that have already been published about how the monkeypox virus affects humans. © 2023, Liaquat University of Medical and Health Sciences. All rights reserved.

10.
Viruses ; 15(4)2023 03 24.
Article in English | MEDLINE | ID: covidwho-2305206

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes cellular trafficking pathways to process its structural proteins and move them to the site of assembly. Nevertheless, the exact process of assembly and subcellular trafficking of SARS-CoV-2 proteins remains largely unknown. Here, we have identified and characterized Rab1B as an important host factor for the trafficking and maturation of the spike protein (S) after synthesis at the endoplasmic reticulum (ER). Using confocal microscopy, we showed that S and Rab1B substantially colocalized in compartments of the early secretory pathway. Co-expression of dominant-negative (DN) Rab1B N121I leads to an aberrant distribution of S into perinuclear spots after ectopic expression and in SARS-CoV-2-infected cells caused by either structural rearrangement of the ERGIC or Golgi or missing interaction between Rab1B and S. Western blot analyses revealed a complete loss of the mature, cleaved S2 subunit in cell lysates and culture supernatants upon co-expression of DN Rab1B N121I. In sum, our studies indicate that Rab1B is an important regulator of trafficking and maturation of SARS-CoV-2 S, which not only improves our understanding of the coronavirus replication cycle but also may have implications for the development of antiviral strategies.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/metabolism , SARS-CoV-2/metabolism , Golgi Apparatus/metabolism , rab1 GTP-Binding Proteins/genetics , rab1 GTP-Binding Proteins/analysis , rab1 GTP-Binding Proteins/metabolism
11.
Coronaviruses ; 2(10) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2277624

ABSTRACT

Coronaviruses are enveloped positive-stranded RNA viruses that cause mild to acute respiratory illness. Coronaviruses can merge envelope proteins with the host cell membranes and de-liver their genetic material. Coronavirus disease 2019 (COVID-19) is the seventh coronavirus clos-est to the severe acute respiratory syndrome (SARS) in bats that infects humans. COVID-19 at-tacks the respiratory system and stimulates the host inflammatory responses, promotes the recruit-ment of immune cells, and enhances angiotensin-converting enzyme 2 (ACE2) activities. Patients with confirmed COVID-19 have experienced fever, dry cough, headache, dyspnea, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID-19-associated mortality. Inflammation is a common and important factor in the pathogenesis of COVID-19. In recent years, stem cell-based therapies represent a promising therapeutic option against various diseases. Mesenchymal stem cells (MSCs) are multipotent stem cells that can self-renew and differentiate into various tissues of mesodermal ori-gin. MSCs can be derived from bone marrow, adipose tissue, and umbilical cord blood. MSCs, with their unique immunomodulatory properties, represent a promising therapeutic alternative against diseases associated with inflammation. Several previous studies have shown that MSCs with a strong safety profile can improve the treatment of patients with COVID-19. The information in this review provides a summary of the prevention and diagnosis of COVID-19. Also, we focus on the current clinical application of MSCs for treatments of patients with COVID-19.Copyright © 2021 Bentham Science Publishers.

12.
Coronaviruses ; 3(5):14-32, 2022.
Article in English | EMBASE | ID: covidwho-2273408

ABSTRACT

COVID-19 is a respiratory infection caused by a newer strain of coronavirus known as SARS-CoV-2. The major problem of COVID-19 infections is the ARDS, followed by respiratory failure, organ failure, and even death with multiple organ dysfunction, including cardiovascular collapse. Moreover, it affects the old age population with co-morbid conditions. The deficiency of diet, micronutrients, and vitamins also plays a key role in diminishing the immune power, and increases the rate of viral infectivity. The possible reasons and management methods are discussed in this review. The management methods enhance the host immune system via multi-functional and multi-targeted actions. The global rate of COVID-19 outbreak necessitates the need to develop newer medicines. The drug discovery process is based on the exposure of viral proteins, genome sequence, replication mechanisms, pathophysiological mechanisms, and host cell components (as a target) reactions. This article highlights the overview of coronavirus components, the replications process, and possible targets for the management of coronavirus infections. It may lead to the rapid development of newer medicines for the treatment of coronavirus in-fections.Copyright © 2022 Bentham Science Publishers.

13.
Coronaviruses ; 3(4) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2272801

ABSTRACT

Coronaviruses are a leading cause of emerging life-threatening diseases, as evidenced by the ongoing coronavirus disease pandemic (COVID-19). According to complete genome sequence analysis reports, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, has a sequence identity highly similar to the earlier severe acute respiratory syndrome coronavirus (SARS-CoV). The SARS-CoV-2 has the same mode of transmission, replication, and pathogenicity as SARS-CoV. The SARS-CoV-2 spike protein's receptor-binding domain (RBD) binds to host angiotensin-converting enzyme-2 (ACE2). The ACE2 is overexpressed in various cells, most prominently epithelial cells of the lung (surface of type 1 and 2 pneumocytes), intestine, liver, kidney, and nervous system. As a result, these organs are more vulnerable to SARS-CoV-2 infection. Furthermore, renin-angiotensin system (RAS) blockers, which are used to treat cardiovascular diseases, intensify ACE2 expression, leading to an increase in the risk of COVID-19. ACE2 hydrolyzes angioten-sin-II (carboxypeptidase) to heptapeptide angiotensin (1-7) and releases a C-terminal amino acid. By blocking the interaction of spike protein with ACE2, the SARS-CoV-2 entry into the host cell and inter-nalization can be avoided. The pathogenicity of SARS-CoV-2 could be reduced by preventing the RBD from attaching to ACE2-expressing cells. Therefore, inhibition or down-regulation of ACE2 in host cells represents a therapeutic strategy to fight against COVID-19. However, ACE2 plays an essential role in the physiological pathway, protecting against hypertension, heart failure, myocardial infarction, acute respiratory lung disease, and diabetes. Given the importance of ACE's homeostatic role, targeting of ACE2 should be realized with caution. Above all, focusing on the SARS-CoV-2 spike protein and the ACE2 gene in the host cell is an excellent way to avoid viral mutation and resistance. The current review summarises the sequence analysis, structure of coronavirus, ACE2, spike protein-ACE2 complex, essential structural characteristics of the spike protein RBD, and ACE2 targeted approaches for anti-coronaviral drug design and development.Copyright © 2022 Bentham Science Publishers.

14.
Coronaviruses ; 2(3):364-368, 2021.
Article in English | EMBASE | ID: covidwho-2272543

ABSTRACT

Background: B814, now's called Coronavirus first identified by Tyrrell and Bynoe in 1965 from the respiratory tract (embryonic tracheal) of an adult and later on during working on National Institutes of Health Robert Chanock used the term "OC" for same virus strain. After several years researchers reported that coronaviruses were caused disease in rats, mice, chickens, turkeys, calves, dogs, cats, rabbits etc. after effecting the enormous variety of animal, in year 2002-2003 it caused new respiratory disease named severe acute respiratory syndrome, (SARS) in southern China. Objective(s): The main objective of this article is to compare the status of various previous pandemics (i.e., SARS, MERS) with the current COVID-19 pandemic in terms of the life cycle, diagnosis process and prevention Results: On 31st December 2019, the World Health Organization (WHO) office in China received information regarding pneumonia cases of unknown etiology from the Wuhan district in central China. Subsequently, this new disease spread to China, and from there, to the rest of the world. By the end of March 2020, more than 2 million cases were confirmed of this new disease, with over 70000 deaths worldwide. After some time, researchers have identified that this new disease is caused by a novel beta-Coronavirus (virus SARS-CoV-2) and the new disease was named COVID-19. Since then, the Ministry of Health of various countries and WHO have been fighting this health emergency, which has not only affected public health, but also affected various economic sectors. Conclusion(s): The current outbreak SARS-CoV-2 phylogenetically resembled to Bat SARS, which was previously identified in year 2002 and 2012 having low mortality rate than MERS and SARS. However, SARS-CoV-2 and MERS having high virological similarity but both use different receptors to take entry in to the host cell via ACE-2 and DPP-4 respectively. Unfortunately, currently there is no approved treatment available worldwide. Currently, we can hope that together we will recover from this public health emergency very soon.Copyright © 2021 Bentham Science Publishers.

15.
Coronaviruses ; 2(12) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2266234

ABSTRACT

The present paper elucidates the conceivable application of two key molecules in SARS-CoV-2 detection of suspected infected persons. These molecules were selected on the basis of the strong interaction between ACE-2 and S protein that allows virus attachment to its host cells;on the other hand, specific immunocompetant effectors are generated by the human immune system during the infection. Several testing procedures are already being used to diagnose SARS-CoV-2 infection, particularly the RT-PCR technique. ELISA and LFIA are possible assays for the employment of shACE-2/ hAc-anti-S (the molecules of interest) as the main agents of the test that confer dual principal functions (capture and detection). The future diagnostic kits involving shACE-2 and hAc-anti-S will possibly be highly sensitive with rapid detection in addition to their advantage of relatively easy conception. They could be largely considered as technically advanced kits in regards to the current SARS-CoV-2 diagnostic immunoassays.Copyright © 2021 Bentham Science Publishers.

16.
Coronaviruses ; 2(4):468-480, 2021.
Article in English | EMBASE | ID: covidwho-2266212

ABSTRACT

Coronavirus disease 2019 named COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been reported in Wuhan city of Hubei Province of China become a global pandemic. Genomic sequencing of SARS-CoV-2 unveils which showed multiple mutations relative to SARS-CoV. SARS-CoV-2 showed a very high receptor-binding domain (RBD) affinity towards the ACE-2 receptor in host cells, similar to SARS. Lack of immediate supervision and diagnostic measures hurdles prevention and treatment strategies against COVID-19. However, from SARS and MERS epidemics, WHO launched SOLIDARITY, a strategic and technical advisory group for infection hazards (STAG-IH) for the regular supervision and alert, which identified the estimated risk of COVID-19 and recommended the health emergence program to respond COVID-19. This article will briefly review the rationale history, structural genome with mutation, pathogenesis, preventive measure, and targeted treatment strategy to handle this pandemic COVID-19.Copyright © 2021 Bentham Science Publishers.

17.
Acta Virologica ; 66(4):332-338, 2022.
Article in English | EMBASE | ID: covidwho-2265386

ABSTRACT

This study aims to fill a knowledge gap in our understanding of Omicron variant receptor-binding domain (RBD) interactions with host cell receptor, angiotensin-converting enzyme 2 (ACE2). Protein-protein docking, scoring, and filtration were all performed using the HDOCK server. A coarse-grained prediction of the changes in binding free energy caused by point mutations in Omicron RBD was requested from the Binding Affinity Changes upon Mutation (BeAtMuSiC) tools. GROMACS was utilized to perform molecular dynamics simulations (MD). Within the 15 mutations in Omicron RBD, several mutations have been linked to increased receptor affinity, immunological evasion, and inadequate antibody response. Wild-type (wt) SARS-CoV-2 and its Omicron variant have 92.27% identity. Nonetheless, Omicron RBD mutations resulted in a slight increase in the route mean square deviations (RMSD) of the Omicron structural model during protein-protein docking, as evidenced by RMSDs of 0.47 and 0.85 A for the wt SARS-CoV-2 and Omicron RBD-ACE2 complexes, respectively. About five-point mutations had essentially an influence on binding free energy, namely G6D, S38L, N107K, E151A, and N158Y. The rest of the mutations were expected to reduce the binding affinity of Omicron RBD and ACE2. The MD simulation supports the hypothesis that Omicron RBD is more stably bound to ACE2 than wt SARS-CoV-2 RBD. Lower RMSD and greater radius of gyration (Rg) imply appropriate Omicron structure 3D folding and stability. However, the increased solvent accessible surface area (SASA) with a greater Omicron shape may have a different interaction with receptor binding and regulate virus entrance. Omicron RBD's mutations help it maintain its structural stability, compactness, ACE2 binding, and immune evasion.Copyright © 2022 AEPress, s.r.o.. All rights reserved.

18.
Coronaviruses ; 2(10) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2261974

ABSTRACT

In December 2019, a new severe acute respiratory coronavirus (SARS-COV-2) had caused outbreaks of pneumonia in Wuhan city, China. It was known as coronavirus infected dis-ease-2019 (COVID-19). COVID-19 patients typically have a fever and respiratory syndrome, where the lung is the main target organ affected by this virus. The objective of this review is to monitor and evaluate injuries caused by the SARS-COV-2 virus on multiple organs other than the lung as the gastrointestinal tract, liver, kidney, heart, ovary, ocular, olfactory, gonad, skin, central nervous system, and sense organs. As SARS-COV-2 virus enters host cells via cell receptor an-giotensin circulating enzyme-2 (ACE2), so it is important to identify the main target cells attacked by SARS-COV-2 virus by comparing the ACE2 expression and viral upload in different organs. In conclusion, the definite role of body organs is explored in the manifestation of COVID-19 infection and crosstalk between other organs are useful tools to find any correlation between disease severity and organs dysfunction, exact prognosis, disease prevention measures, clinical care, and treatment strategies.Copyright © 2021 Bentham Science Publishers.

19.
Current Traditional Medicine ; 9(5) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-2256455

ABSTRACT

Coronavirus disease 2019 (COVID-19), named by WHO, is a real public health disaster of the third millennium. This highly contagious viral disease has infected the world population and is now a global pandemic. This acute respiratory distress syndrome (ARDS) has severe complica-tions like pneumonitis, respiratory failure, shock, multiorgan failure, and death. Well-defined FDA-approved synthetic is not yet available. Case management strategies like lockdown, use of masks and sanitizers, social distancing, and repurposing of antiviral drugs were initially undertaken to cope with this pandemic. Different broad-spectrum antiviral drugs are being repurposed as one of the treatment modalities. The global vaccination programme with the newly launched COVID-19 vac-cines, Covishield, covaxin, sputnik V, etc., is an ongoing process. Simultaneously, significant research is being carried out in search of natural antivirals and evaluating the potency of food bioac-tives to aid naturistic protection against the coronavirus. This mini-review has compiled the latest updates on the screening and evidence-based mechanistic evaluation of phytochemicals and food bioactives as non-pharmacological adjuvant aid in COVID pandemics.Copyright © 2023 Bentham Science Publishers.

20.
Coronaviruses ; 2(6) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2252665

ABSTRACT

Background: The recent serious outbreak of Covid-19 has required urgent medical treat-ments for numerous patients. No clinically active vaccines or antiviral agents are available for Covid-19. According to several studies, Chloroquine (CQ) and Hydroxychloroquine (HCQ) have shown potential as Covid-19 antivirals, especially when administered with Azithromycin (AZM). Objective(s): Here, we review the rationale behind this use. CQ/HCQ is effective against Covid-19 in--vitro and in-vivo laboratory studies. Therapy in Covid-19 infected patients with CQ/HCQ is supported by evidence of trials and field experiences from multiple sources. Method(s): The relevant works are reviewed. The presence or absence of conflict of interest is weighed against the conclusions. Result(s): CQ/HCQ has been used with success in mild cases or medium severity cases. No randomized controlled trial has, however, been conducted to support the safety and efficacy of CQ/HCQ and AZM for Covid-19. Prophylaxis with CQ/HCQ is more controversial but generally not having side effects and supported by pre-clinical studies. The mechanism of action against Covid-19 is unclear. More research is needed to understand the mechanisms of actions CQ/HCQ has against Covid-19 infection, and this requires investigations with nanoscale imaging of viral infection of host cells. Conclusion(s): Most of the published works indicate CQ/HCQ is likely effective against Covid-19 in-fection, almost 100% in prophylaxis and mild to medium severity cases, and 60% in late infection cases. The percentage of positive works is larger if works conducted under a probable conflict of interest are excluded from the list.Copyright © 2021 Bentham Science Publishers.

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