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1.
Front Cell Infect Microbiol ; 12: 1003608, 2022.
Article in English | MEDLINE | ID: covidwho-2109735

ABSTRACT

As new pathogens emerge, new challenges must be faced. This is no different in infectious disease research, where identifying the best tools available in laboratories to conduct an investigation can, at least initially, be particularly complicated. However, in the context of an emerging virus, such as SARS-CoV-2, which was recently detected in China and has become a global threat to healthcare systems, developing models of infection and pathogenesis is urgently required. Cell-based approaches are crucial to understanding coronavirus infection biology, growth kinetics, and tropism. Usually, laboratory cell lines are the first line in experimental models to study viral pathogenicity and perform assays aimed at screening antiviral compounds which are efficient at blocking the replication of emerging viruses, saving time and resources, reducing the use of experimental animals. However, determining the ideal cell type can be challenging, especially when several researchers have to adapt their studies to specific requirements. This review strives to guide scientists who are venturing into studying SARS-CoV-2 and help them choose the right cellular models. It revisits basic concepts of virology and presents the currently available in vitro models, their advantages and disadvantages, and the known consequences of each choice.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cell Line , China
2.
Materials Today Physics ; 28, 2022.
Article in English | Web of Science | ID: covidwho-2105625

ABSTRACT

The deadly viruses, which are spreading worldwide at an alarming rate, are a major challenge for the life sci-ences. More efficient and cost-effective methods with fewer side effects can provide a good alternative to traditional drug-based methods. Currently, physical phenomena such as light in the form of photodynamic action are increasingly being used to inactivate viruses. Photodynamic inactivation (PDI) uses a photosensitizer (PS), light, and oxygen to generate reactive oxygen species (ROS) to inactivate microorganisms. This article reviews the use of existing PSs, as one of the essential anti-viral agents, and introduces new materials and strategies combined with PDI. Physiochemical properties of PSs and their role in interaction with virus components are discussed. Furthermore, the effectiveness of optical sensitizers with radiation methods to inactivate viruses is highlighted.

3.
Phytother Res ; 2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2103698

ABSTRACT

The worldwide spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to health, economic, environmental, and social aspects of human lives. Currently, there are no approved treatments that can effectively block the virus although several existing antimalarial and antiviral agents have been repurposed and allowed use during the pandemic under the emergency use authorization (EUA) status. This review gives an updated overview of the antiviral effects of phytochemicals including alkaloids, flavonoids, and terpenoids against the COVID-19 virus and their mechanisms of action. Search for natural lead molecules against SARS-CoV-2 has been focusing on virtual screening and in vitro studies on phytochemicals that have shown great promise against other coronaviruses such as SARS-CoV. Until now, there is limited data on in vivo investigations to examine the antiviral activity of plants in SARS-CoV-2-infected animal models and the studies were performed using crude extracts. Further experimental and preclinical investigations on the in vivo effects of phytochemicals have to be performed to provide sufficient efficacy and safety data before clinical studies can be performed to develop them into COVID-19 drugs. Phytochemicals are potential sources of new chemical leads for the development of safe and potent anti-SARS-CoV-2 agents.

4.
Microbiol Spectr ; : e0349022, 2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2097941

ABSTRACT

We newly generated two human induced pluripotent stem cell (hiPSC)-derived spheroid lines, termed Spheroids_4MACE2-TMPRSS2 and Spheroids_15M63ACE2-TMPRSS2, both of which express angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are critical for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both spheroids were highly susceptible to SARS-CoV-2 infection, and two representative anti-SARS-CoV-2 agents, remdesivir and 5h (an inhibitor of SARS-CoV-2's main protease), inhibited the infectivity and replication of SARS-CoV-2 in a dose-dependent manner, suggesting that these human-derived induced spheroids should serve as valuable target cells for the evaluation of anti-SARS-CoV-2 activity. IMPORTANCE The hiPSC-derived spheroids we generated are more expensive to obtain than the human cell lines currently available for anti-SARS-CoV-2 drug evaluation, such as Calu-3 cells; however, the spheroids have better infection susceptibility than the existing human cell lines. Although we are cognizant that there are human lung (and colonic) organoid models for the study of SARS-CoV-2, the production of those organoids is greatly more costly and time consuming than the generation of human iPSC-derived spheroid cells. Thus, the addition of human iPSC-derived spheroids for anti-SARS-CoV-2 drug evaluation studies could provide the opportunity for more comprehensive interpretation of the antiviral activity of compounds against SARS-CoV-2.

5.
Middle East Fertil Soc J ; 25(1): 31, 2020.
Article in English | MEDLINE | ID: covidwho-2098487

ABSTRACT

BACKGROUND: The potential of COVID-19 severe pandemic necessitates the development of an organized and well-reasoned plan for the management of embryology/andrology laboratories while safeguarding the wellbeing of patients and IVF staff. MAIN BODY: A COVID-19 pandemic response plan was proposed for embryology and andrology laboratories for pre-pandemic preparedness and pandemic management in anticipation of a possible second coronavirus wave. Preparation involves many plans and logistics before a pandemic risk rises. Many operational changes can be considered during the pandemic. This plan includes logistical arrangements, reducing labor needs, conserving supplies, and protective measures for embryologists and gametes/embryos. CONCLUSION: The unpredictable emergence of the COVID-19 pandemic dictates the need for a preparedness plan for embryology/andrology laboratories, which includes an action-oriented plan to secure the safety of all stakeholders.

6.
Journal of Drug Delivery Science and Technology ; : 103930, 2022.
Article in English | ScienceDirect | ID: covidwho-2095604

ABSTRACT

Organ-on-a-chip is a three-dimensional microfluidic system that simulates the cellular structure and biological milieu of an organ, that seemed to be constructed and studied substantially in the last decade. Microchips can be configured to suit disease states in a variety of organs, including the lung. When contrasted to traditional in vitro models like monolayer cell lineages, lung-on-a-chip models lays out a pragmatic portrayal of disease pathophysiology and pharmaceuticals’ mode of action, and this is especially more prevailing in connection with the COVID-19 pandemic. Animal models have typically been used in pharmaceutical drug screening to assess pharmacological and toxicological reactions to a new entity. These adaptations, on the other hand, do not precisely represent biological reactions in humans. Present and prospective uses of the lung-on-a-chip model in the pulmonary system are highlighted in this overview. In addition, the constraints of existing in vitro systems for respiratory disease simulation and therapeutic discovery would be emphasized. Attributes of lung-on-a-chip transformative features in biomedical applications will be addressed to illustrate the relevance of this lung-on-chip model for medical science.

7.
Curr Stem Cell Rep ; 8(4): 151-163, 2022.
Article in English | MEDLINE | ID: covidwho-2085779

ABSTRACT

Purpose of Review: Organoids are an emerging technology utilizing three-dimensional (3D), multi-cellular in vitro models to represent the function and physiological responses of tissues and organs. By using physiologically relevant models, more accurate tissue responses to viral infection can be observed, and effective treatments and preventive strategies can be identified. Animals and two-dimensional (2D) cell culture models occasionally result in inaccurate disease modeling outcomes. Organoids have been developed to better represent human organ and tissue systems, and accurately model tissue function and disease responses. By using organoids to study SARS-Cov-2 infection, researchers have now evaluated the viral effects on different organs and evaluate efficacy of potential treatments. The purpose of this review is to highlight organoid technologies and their ability to model SARS-Cov-2 infection and tissue responses. Recent Findings: Lung, cardiac, kidney, and small intestine organoids have been examined as potential models of SARS-CoV-2 infection. Lung organoid research has highlighted that SARS-CoV-2 shows preferential infection of club cells and have shown value for the rapid screening and evaluations of multiple anti-viral drugs. Kidney organoid research suggests human recombinant soluble ACE2 as a preventative measure during early-stage infection. Using small intestine organoids, fecal to oral transmission has been evaluated as a transmission route for the virus. Lastly in cardiac organoids drug evaluation studies have found that drugs such as bromodomain, external family inhibitors, BETi, and apabetalone may be effective treatments for SARs-CoV-2 cardiac injury. Summary: Organoids are an effective tool to study the effects of viral infections and for drug screening and evaluation studies. By using organoids, more accurate disease modeling can be performed, and physiological effects of infection and treatment can be better understood.

8.
Chinese Journal of Virology ; 37(6):1376-1384, 2021.
Article in Chinese | GIM | ID: covidwho-2081014

ABSTRACT

Infectious Bronchitis Virus (1BV) belongs to the y coronavirus, however, the function of IBV encoded endoribonuclease (non - structural protein 15, nsp15) has not been determined yet. To explore the function of nsp15 in the process of IBV replication, we mutated the IBV nsp15 endonuclease core residue His238 to Ala, constructed the nsp15-defective recombinant virus rIBV-nsp15-H238A, via in vitro ligation and recombination technology. Plaque assay and TCID50 were performed to measure virus titer, virus plaque size and growth curve. The IBV Beaudette-R genome was cloned as 5 fragments in vectors, BsaI or BsmBI restriction sites were added to the end of each fragment. After plasmid amplification, the cDNA fragments were obtained by enzymatic digestion, followed with in vitro ligation and transcription. Full - length genomic RNA was electroporated into Vero cells, together with N transcript, to rescue the recombinant viruses rIBV and rIBV - nsp15- H238A. Plaque assay was performed to detect and compare the viral titer and plaque size of these two recombinant viruses. Results showed that the virus titer of rIBV -nsp15 -H238A was 2.71x106PFU/mL, 3 times lower than that of rIBV (9.4x106PFU/mL). The plaque size of rIBV-nsp15-H238A was much smaller than that of rIBV, indicating that rIBV-nsp15-11238A replicates and spreads slower than rIBV. The growth curve of rIBV-nsp15-H238A was slower than that of rIBV. Our study demonstrates that nsp15 I-1238 is the key amino acid and plays an important role in the replication and spread of IBV. The construction of nsp15 defective recombinant virus provides a powerful tool for the study of the function of nsp15.

9.
Zeitschrift fur Arznei & Gewurzpflanzen ; 25(4):153-156, 2020.
Article in German | CAB Abstracts | ID: covidwho-2073887

ABSTRACT

This paper presents the results of studies con ducted to determine the biologically active compounds of some Mexican desert plants (Florensia cernua, Larrea tridentata and Lippia graveolens) against the protease Mpro and the replicase RdRp of SARS coronavirus-2 using in silico molecular docking method. Results showed that against Mpro, luteolin-7-O-glucoside (L. graveolens) has the highest binding energy, followed by kaempferol and quercetin (L. tridentata). The values determined were higher than those detected in the antiviral chemical compounds lopinavir and ribavirin. Also, the binding energy of luteolin-7-O-glucoside against RdRp was higher than that in remdesivir, lopinavir and ribavirin. The compounds nordihydroguajaretic acid and kaempferol from L. tridentata and 3,8,8'-trimethoxy-3'-(1-iperidinyl)-2,2'-binaphthalene-1,1',4,4'-tetrone from F. cernua also showed a higher affinity potential against RdRp than the antiviral drugs. based on the results, the compounds present in the semi-desert plants acted as potential inhibitors against the Mpro and RdRp proteins of the SARS coronavirus 2 (SARS-CoV-2).

10.
Int J Mol Sci ; 23(20)2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2071505

ABSTRACT

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 Mpro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC50). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC50 value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC50 values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 Mpro enzyme was investigated by utilizing the SARS-CoV-2 Mpro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 Mpro inhibitory potential was attained for fondaparinux sodium with an IC50 value of 2.36 µM, surpassing the reference tipranavir (IC50 = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 Mpro inhibitory potential was attained for dabigatran with an IC50 value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/drug therapy , Molecular Docking Simulation , Coronavirus 3C Proteases , Molecular Dynamics Simulation , Fondaparinux , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Dabigatran , Ticagrelor , Eptifibatide , Gentian Violet , Protease Inhibitors/chemistry , Viral Nonstructural Proteins/metabolism , Heparin/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry
11.
Annals of Phytomedicine-an International Journal ; 10:29-40, 2021.
Article in English | Web of Science | ID: covidwho-2072558

ABSTRACT

The exploration for various effective antiviral agents is pressing issue regarding the histrionic circumstances of the global COVID pandemic, a blowout of SARS-CoV-2 virus disease. Actual antiviral remedies are not existing at present and the agreed remedy available for COVID somewhat has not been well recognized yet. In these circumstances, there is a need of more consideration which should be given to the exploration for all possible antiviral agents existing in nature. Though, the algae (marine/fresh water) are one of the richest reservoirs of bioactive complexes yet they are sporadically been studied as antiviral agents. In past, the bioactive compounds of algal origin have demonstrated remarkable in vitro antiviral activity against the HIV and HCV. The present article recapitulates the antiviral possessions of algae or their extracts that have been studied in several in vitro/in vivo animal system-based studies, with the aim that the vast algal diversity should get the due attentions related to the deterrence of SARS-CoV-2.

12.
Annals of Phytomedicine-an International Journal ; 10:12-28, 2021.
Article in English | Web of Science | ID: covidwho-2072557

ABSTRACT

Viral infections are contagious and deadly. Many viral attacks in the past decades including COVID-19 have turned into pandemics and cost millions of lives. Treatment to virus is difficult as they transform themselves into many variants. Thus, an intelligent way of keeping oneself out of the trouble is through better nutrition that enhance immune responses. Foods that provide high quantities of nutrients are vegetables, fruits and nuts. They are rich in fibres, fats, protein, vitamins, minerals and plant bioactive compounds like phytosterols, polyphenolics, flavonoids, etc. Many studies and randomised control trials have proven their therapeutic effects and health promoting capacities. These compounds interfere with the pathways of metabolic mechanisms in the human body and work by either providing a protective scope or by destroying any harmful incomings into the body;that would disrupt the homeostasis. In this article, nuts and their nutritive components that administer healthy benefits are discussed. Almonds, cashew nuts, pistachios, peanuts, chestnuts and Brazil nuts are examined and reviewed here. The nutritional composition of these nuts and their mechanism to offer medicinal properties are explained in detail. Apart from nutritional values, these nuts are rich source of antioxidants that confer anti-inflammatory and immunomodulatory features. These activities enhance the immune responses by activating the defense mechanisms. Apart from the intake of highly nutritious diet, practising social distancing, isolation and better sanitation procedures are highly beneficial to avoid the severity of the viral attacks.

13.
Viruses ; 14(10)2022 09 27.
Article in English | MEDLINE | ID: covidwho-2066543

ABSTRACT

Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light at 445 nm in a photodynamic therapy approach. Curcumin at a concentration of 10 µM, delivered to the virus prior to inoculation on cell culture, inhibited SARS-CoV-2 replication (reduction >99%) in Vero E6 cells, possibly due to disruption of the virion structure, as observed using the RNase protection assay. However, curcumin was not effective as a prophylactic treatment on already-infected Vero E6 cells. Notably, when curcumin was employed as a photosensitizer and blue laser light at 445 nm was delivered to a mix of curcumin/virus prior to the inoculation on the cells, virus inactivation was observed (>99%) using doses of curcumin that were not antiviral by themselves. Photodynamic therapy employing crude curcumin can be suggested as an antiviral option against SARS-CoV-2 infection.


Subject(s)
COVID-19 , Curcumin , Chlorocebus aethiops , Animals , Humans , SARS-CoV-2 , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Curcumin/pharmacology , COVID-19/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Vero Cells , Anti-Inflammatory Agents/pharmacology , Ribonucleases/pharmacology , Virus Replication
14.
Journal of Clinical and Diagnostic Research ; 16(9):DC12-DC17, 2022.
Article in English | EMBASE | ID: covidwho-2067199

ABSTRACT

Introduction: Bharat Biotech International Ltd in partnership with National Institute of Virology (NIV), has developed an indigenous whole virion inactivated Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) viral vaccine BBV-152 (Covaxin), formulated with Toll Like Receptors 7/8 agonist Imidazoquinoline (IMDG) molecule adsorbed to alum (Algel). Variety of factors other than environmental ones can affect vaccines efficiency outside the strict setting of clinical trials, like how the vaccine is stored or transported, and even how patients are vaccinated. In addition, the intrinsic capacity of the recipient to respond to a vaccine which is determined by sex, genetic factors, age, psychological stress, nutrition and other diseases are also likely to have an impact. Aim(s): To determine the safety, reactogenicity and immunogenicity of the inactivated whole virus vaccine (Covaxin) amongst hospital-based population groups. Material(s) and Method(s): The prospective analytical study was conducted in the Department of Microbiology, Sawai Man Singh Medical College, Jaipur, Rajasthan, India, from January 2021 to March 2021.The study primarily included Healthcare Workers (HCWs) employed at SMS Medical college and attached hospitals. In-vitro quantitative IgG antibodies against SARS-CoV-2 spike Receptor Binding Domain (RBD) were measured using Chemiluminescence Immunoassay (CLIA) based Advia centaur SARS-CoV-2 IgG, manufactured by Siemens Pvt Ltd, Munich, Germany, as per manufacture's instructions. Result(s): Out of total 223 individuals, 61.88 % (138/223) showed neutralising antibody titre of >1 index value by CLIA, rest 38.12% (85/223) were non reactive i.e., titre <1 index value, after four weeks of receiving first dose of Covaxin. After 2 to 4 weeks of receiving second dose 84.30% (188/223) showed neutralising antibody titre of >1 index value by CLIA, rest 15.70% (35/223) were non reactive i.e., titre <1 index value. After receiving first dose, 100% (223/223) of the participants developed localised pain and bodyache 33.63% (75/223). None of the participants showed any anaphylactic reaction or any emergency condition just after vaccination. Conclusion(s): Covaxin is a well-tolerated vaccine, and induces good humoral response against SARS-CoV-2 with a significant rise in the neutralising antibody titres. Copyright © 2022 Journal of Clinical and Diagnostic Research. All rights reserved.

15.
Vet Res ; 53(1): 70, 2022 Sep 06.
Article in English | MEDLINE | ID: covidwho-2064844

ABSTRACT

Bovine respiratory disease (BRD) is one of the most important diseases impacting the global cattle industry, resulting in significant economic loss. Commonly referred to as shipping fever, BRD is especially concerning for young calves during transport when they are most susceptible to developing disease. Despite years of extensive study, managing BRD remains challenging as its aetiology involves complex interactions between pathogens, environmental and host factors. While at the beginning of the twentieth century, scientists believed that BRD was only caused by bacterial infections ("bovine pasteurellosis"), we now know that viruses play a key role in BRD induction. Mixtures of pathogenic bacteria and viruses are frequently isolated from respiratory secretions of animals with respiratory illness. The increased diagnostic screening data has changed our understanding of pathogens contributing to BRD development. In this review, we aim to comprehensively examine experimental evidence from all existing studies performed to understand coinfections between respiratory pathogens in cattle. Despite the fact that pneumonia has not always been successfully reproduced by in vivo calf modelling, several studies attempted to investigate the clinical significance of interactions between different pathogens. The most studied model of pneumonia induction has been reproduced by a primary viral infection followed by a secondary bacterial superinfection, with strong evidence suggesting this could potentially be one of the most common scenarios during BRD onset. Different in vitro studies indicated that viral priming may increase bacterial adherence and colonization of the respiratory tract, suggesting a possible mechanism underpinning bronchopneumonia onset in cattle. In addition, a few in vivo studies on viral coinfections and bacterial coinfections demonstrated that a primary viral infection could also increase the pathogenicity of a secondary viral infection and, similarly, dual infections with two bacterial pathogens could increase the severity of BRD lesions. Therefore, different scenarios of pathogen dynamics could be hypothesized for BRD onset which are not limited to a primary viral infection followed by a secondary bacterial superinfection.


Subject(s)
Bovine Respiratory Disease Complex , Cattle Diseases , Coinfection , Pasteurella Infections , Respiratory Tract Diseases , Superinfection , Virus Diseases , Animals , Bacteria , Cattle , Cattle Diseases/microbiology , Coinfection/veterinary , Pasteurella Infections/veterinary , Respiratory System , Respiratory Tract Diseases/veterinary , Superinfection/veterinary , Virus Diseases/veterinary
16.
American Journal of Transplantation ; 22(Supplement 3):908, 2022.
Article in English | EMBASE | ID: covidwho-2063434

ABSTRACT

Purpose: To determine if IgM has a direct effect in preventing SARS-CoV-2 replication in Vero E6 cells, and delaying or preventing disease in infected K18- hACE2 mice. Method(s): 1) Vero E6 cells, grown to confluence in 12 well plates, were used to test the effect of IgM in reducing the number of plaque-forming units (PFU).There were 4 groups: a) 25PFU WA-1 SARS-CoV-2 was combined with 20, 5 or 0.8mug IgM in growth medium, and incubated for 1hr in a final volume of 500ul. 100mul was added to Vero E6 cells in replicate wells and incubated for 1hr;b) 100mul of 20, 5 or 0.8mug IgM was added to Vero E6 cells and incubated. Media was aspirated and the cells were then inoculated with 25PFU WA-1 and incubated for 1hr;c) Virus control - as above, but with no IgM;d) No virus or IgM. FBS growth medium containing Avicel was overlain in the wells and incubated for 48 hours. Virus replication was stopped by incubating with 10% buffered formalin. Following removal of formalin, plates were stained with Giemsa violet, dried, and photographed. 2) A COVID -19 Spike- ACE2 binding assay kit was used to determine if IgM (2ug, 4.5ug, 20ug, 45ug IgM) inhibits the interaction between the Spike-receptor binding domain (S-RBD) and Angiotensin I ConvertingEnzyme 2 (ACE2) receptor. 3) K18-hACE2 mice were divided into 3 groups based on treatment regimen;Group 1: with IgM, No virus;2: with Saline, with virus;3: with IgM, with virus. 35ug IgM was injected intraperitoneal in a single dose, 2 days prior to infection. Mice were innoculated intranasally with 1250 pfu of HK SARS-CoV-2. Result(s): 1) Exposure of 25PFU SARS-CoV-2 to IgM (at all concentrations) prior to incubation with Vero E6 cells, inhibited its replication in Vero E6 cells. When Vero E6 cells were incubated with IgM prior to infection, no plaques were seen in wells with 20ug and 5ug IgM but were observed in wells with 0.8ug IgM. Plaques were also observed in the Virus alone group, but none were seen in the 'No IgM-No virus' group. 2) 45ug IgM/100uls inhibited the binding of S-RBD to ACE2 by ~94-100%, 20ug IgM/100uls inhibited it by ~80%, and 2 or 4.5ug/100ul by ~70-75%. Control without IgM did not inhibit the S-RBD-ACE-2 binding. 3) Pretreatment with a single low dose IgM injection delayed weight loss and mortality. Conclusion(s): IgM inhibits the replication of SARS-CoV-2 in Vero cells in vitro. It also inhibits the interaction between S-RBD that is present on the viral surface and the ACE2 receptor, by binding to S-RBD. A single low dose of IgM given prechallenge delayed disease in infected mice. The discovery that IgM interferes with the formation of the S-RBD-ACE2 complex, and that a single low dose can delay disease, indicates its translational potential as a vaccine/therapeutic to prevent or treat COVID-19.

17.
Pharmaceutical Journal ; 306(7949), 2022.
Article in English | EMBASE | ID: covidwho-2064958
18.
Pharmaceutical Journal ; 304(7938), 2022.
Article in English | EMBASE | ID: covidwho-2064892

ABSTRACT

The novel coronavirus (SARS-CoV-2) infection, more commonly referred to as COVID-19,has rapidly developed into a worldwide pandemic with a significant health burden. At the time ofpublication (23 June 2020) there are no approved pharmacological treatments or preventativetherapeutic strategies in place to combat the infection. However, globally, hundreds of clinical studiesthat aim to discover effective COVID-19 treatments are ongoing. This article summarises the rationalebehind several of these interventional trials, including evidence from in vitro studies, and early resultsto provide an insight into the global response. As patients are being enrolled in clinical trials across theUK, some of the safety and practical considerations for the investigational medicines that pharmacistsare most likely to encounter in practice are discussed as part of this review. Copyright © 2020 Pharmaceutical Press. All right reserved.

19.
Tissue Engineering - Part A ; 28:391, 2022.
Article in English | EMBASE | ID: covidwho-2062830

ABSTRACT

Purpose/Objectives: Acute and chronic respiratory diseases constitute a substantial socioeconomic burden on a global scale, as made abundantly clear in the last two years with the rampant coronavirus disease 2019 (COVID-19) pandemic. Alas, the development of new therapies for pathological respiratory conditions has been hindered by the inadequacy of current preclinical models, which often fail to provide reliable predictions on drug safety and efficacy in humans. In particular, considerable anatomical and physiological differences between the respiratory systems of commonly used animal models and humans are one of the main issues leading to high drug attrition and clinical failure rates. Accordingly, the generation of physiologically relevant preclinical lung models for early drug development and pharmaceutical research is urgently needed. In this work, poly(ϵ-caprolactone) (PCL) and gelatin were used as raw materials to produce electrospun scaffolds for in vitro lung tissue engineering, in order to generate human biomimetic platforms for preclinical drug safety and efficacy testing. Methodology: PCL and gelatin were mixed at varying volume ratios: 1:0 (PP), 6:1 (PPG61), 4:1 (PPG41), and 2:1 (PPG21), so as to determine the optimal gelatin concentration for cell adhesion and growth. Poly(vinylpyrrolidone) (PVP) was added to every polymer mixture to facilitate the electrospinning process, and electrospun fibrous matrices were fabricated using a needleless electrospinning technique. Scaffold morphology, chemical composition, and wettability were characterized with scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and water contact angle analysis, respectively. Biocompatibility testing was performed using human bronchial (16HBE) and alveolar (A549) epithelial cell lines, consisting of cell metabolic activity, proliferation, and adhesion evaluation over two weeks of in vitro culture. Results: All polymer blends resulted in the formation of electrospun scaffolds with a nanofibrous structure. The addition of gelatin in PPG61 scaffolds improved fiber morphology compared to PP formulations, but increasing proportions of this polymer in PPG41 and PPG21 mats caused a larger number of defects, such as beading and branching. FTIR analysis confirmed the presence of PCL and PVP in PP scaffolds, as well as the addition of gelatin in all PPG blends. Moreover, as expected, all scaffolds were hydrophilic, with water contact angles below 90°, being suitable for protein adsorption and cell adhesion. Regarding 16HBE and A549 cell viability, surprisingly, no major differences were found between the different formulations over the two-week culture period, showing that all polymer blends were equally capable of promoting cell adhesion and growth. While PP scaffolds significantly outperformed PPG electrospun mats in early timepoints, no such differences were identified at the end of the experimental period. Conclusion/Significance: These results suggested that PCL, PVP, and/or gelatin blend electrospun scaffolds are conducive to lung epithelial cell adhesion and proliferation. Nevertheless, further studies investigating epithelial cell differentiation and function should be conducted to fully assess the suitability of these biomaterials as platforms for in vitro lung tissue engineering.

20.
Tissue Engineering - Part A ; 28:359, 2022.
Article in English | EMBASE | ID: covidwho-2062828

ABSTRACT

Purpose/Objectives: Nature efficiently self-organizes cells and tissues into complex fractal forms. Whether fractal patterning contributes functionally to maturation, and how cells sense and interpret such shape cues, is not well understood. Methodology: Using kidney podocytes as a model system, bioinspired templating of glomerular histology was leveraged to design controlled fractal 21/2 -D surfaces for cell culture. Results: Microcurvature was associated with charge density gradients in space, found to direct extracellular matrix protein organization resulting in hierarchical assembly of cell structures and fractally-branching podocyte morphology in vitro, that was delineated clearly in vitro with a novel highresolution fluorescent assaying technique. Shape stimulation was uniquely associated with development of mature-like foot processes and organized ECM. In applications of drug testing, coronavirus infection, and a cells-as-sensors approach to patient serum diagnostics, fractally stimulated cells were more responsive than flat cultures. Conclusion/Significance: Fractal frameworks may thus provide a functional role in podocyte maturation and could serve to advance other bioengineered systems.

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