Virology: Current Research

ISSN: 2736-657X

Open Access

Current Issue

Volume 6, Issue 2 (2022)

    Mini Review Pages: 1 - 2

    Immune Response to Human Rhinovirus C in Highly Differentiated Human Airway Epithelial Cells

    Yu Jin* and Xin-hui Yuan

    DOI: 10.37421/2736-657X.2022.6.146

    Rhinovirus C (HRV-C) cannot be propagated in immortalized cells, and there is relatively little information on host cell responses to HRV-C infection. Human Bronchial Epithelial (HBE) cells are cultured at the Air-liquid Interface (ALI), which can form tight junctions, produce mucin, and differentiate to form cilia, representing an almost native cell system study HRV-C infections in vitro. In the present study, four strains of HRV-C from infectious clones and clinical specimens were infected with HBE-ALI cells. We found that they induced very similar immune responses, showing that the comparison basis was homogeneous.

    Volume 6, Issue 4 (2022)

      Review Pages: 1 - 1

      A Viable Method for Tracking Down HIV/AIDS Diseases

      Baolan Hu*

      DOI: 10.37421/2736-657X.2022.6.160

      To portray epidemiological examples and spatial transports of HIV/Helps among more prepared adults (developed ≥50) in Sichuan Territory, China during 2008-19, and give sensible reference to HIV/Helps contravention, intercession and treatment. HIV, the causative microorganism of Helps, was first uncovered in 1981 and has been seen as one of the most dangerous powerful diseases overall for a seriously prolonged stretch of time, with a serious impact on broad prosperity [1].

      Mini Review Pages: 1 - 1

      HIV Patients on Antiretroviral Therapy in Care

      Baolan Hu*

      DOI: 10.37421/2736-657X.2022.6.157

      Digestive ailment and Helps (Helps), both achieved by the human immunodeficiency disease (HIV), are two of the world's most serious clinical issues today. Wilderness fever is an infection spread by mosquitos. Mosquitoes are carriers of the contamination resulting to stinging a stomachic human. Wilderness fever centers around the liver and spreads through the course, impacting all organs and in the end killing the individual.

      Volume 6, Issue 6 (2022)

        Mini Review Pages: 1 - 1

        A Mini Review on Viral Pathogens in Gastric Cancer

        Narayana Seth*

        DOI: 10.37421/2736-657X.2022.6.166

        It is assessed that somewhere in the range of 15% and 20% of all human malignant growths overall are brought about by irresistible specialists. Seven infections [Epstein- Barr infection (EBV), hepatitis B infection, human papillomavirus (HPV), Lymphocyte lymphotropic infection, hepatitis C infection, Kaposi's sarcoma infection (KHSV)/human herpesvirus 8 (HHV-8), and Merkel cell polyomavirus] cause 12% of these tumors. Infections are involved at different phases of the carcinogenesis pathway relying upon the viral microorganism and logical require co-factors [e.g., smoking, contraceptives, sustenance, co-disease with herpesvirus and Chlamydia, human immunodeficiency infection (HIV) in cervical danger, liquor, and aflatoxin in hepatocellular carcinoma] to set off neoplasia. This incorporates growth inception by coordination of the viral DNA into the host genome causing upregulation of cell oncogene articulation, viral advancement of DNA harm, chromosomal flimsiness, and dysregulation of cell processes (multiplication, apoptosis, and replicative everlasting status) by viral proteins. Some infections e.g., HBV and HCV, cause hepatocellular carcinoma by roundabout means i.e., ongoing aggravation over many years enhanced by co-variables of aflatoxin and liquor. Another instrument that is key to viral carcinogenesis is the collaboration with the resistant framework with the subsequent evolvement of safe avoidance procedures.

        Volume 5, Issue 1 (2021)

          Research Pages: 1 - 6

          Direct ACE2- Spike RBD Binding Disruption With Small Molecules: A Strategy For COVID-19 Treatment

          Bartlomiej P. Przychodzen*, Sandra P. Smieszek, Christos M. Polymeropoulos, Vasilios M. Polymeropoulos and Mihael H. Polymeropoulos

          ACE2 is a key receptor for SARS-CoV-2 cell entry. Binding of SARS-Cov-2 to ACE2 involves the viral Spike protein. The molecular interaction between ACE2 and Spike has been resolved. Interfering with this interaction might be used in treating patients with COVID-19. Inhibition of this interaction can be attained via multiple routes: here we focus on identifying small molecules that would prevent the interaction. Specifically we focus on small molecules and peptides that have the capacity to effectively bind the ACE2: RBD contact domain to prevent and reduce SARS-CoV-2 entry into the cell. We aim to identify molecules that prevent the docking of viral spike protein (mediated by RBD) onto cells expressing ACE2, without inhibiting the activity of ACE2. We utilize the most recent ACE2-RBD crystallography resolved model (PDB-ID: 6LZG). Based on animal susceptibility data we narrowed down our interest to the location of amino acid 34 (Histidine) located on ACE2. We performed an in silico screen of a chemical library of compounds with several thousand small molecules including FDA approved compounds. All compounds were tested for binding to the proximal binding site located close to histidine 34 on ACE2. We report a list of four potential small molecules that potentially have the capacity to bind target residue: AY-NH2, a selective PAR4 receptor agonist peptide (CAS number: 352017-71-1), NAD+ (CAS number: 53- 84-9), Reproterol, a short-acting β2 adrenoreceptor agonist used in the treatment of asthma (CAS number: 54063-54-6), and Thymopentin, a synthetic immune- stimulant which enhances production of thymic T cells (CAS number: 69558-55-0). The focus is on a High Throughput Screen Assay (HTSA), or in silico screen, delineating small molecules that are selectively binding/masking the crucial interface residue on ACE2 at His34. Consequently, inhibiting SARS-CoV-2 binding to host ACE2 and viral entry is a potent strategy to reduce cellular entry of the virus. We suggest that this anti-viral nature of this interaction is a viable strategy for COVID19 whereas the small molecules including peptides warrant further in vitro screens.

          Research Article Pages: 1 - 6

          In silico Docking for Inhibition Neuropilin-1 (Sars-Cov-2 Receptor) by Some Natural Compound and Approved Drugs

          Mohamed Gomaa Seadawy*, Mohamed Shamel Eldesoky, Aya Ahmed and Abdel Rahman Nabwi Zekri

          Background: Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. Beside its role in cancer, NRP-1 is a reported entrance for several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19).

          Methods: We made Insilco docking between the spike protein and Neuropilin-1 using Cluspro 2.0 software. Therefore, Neuropilin-1 becomes host factor for SARSCoV- 2 infection. Then by using molecular docking, we test nine compounds against Neuropilin-1 for its inhibition.

          Results and Conclusion: Our study revealed that some drugs and natural compounds success in inhibition of binding between the virus and its new receptor with Insilco docking data.

          Mini Review Pages: 1 - 3

          Establishing PCR Testing in Nepal for COVID-19: Challenges and Opportunities

          Ram Bahadur Khadka

          Polymerase Chain Reaction (PCR) invented by Kary Mullis (1983), has become the centrepiece of molecular detection of various infectious diseases including coronavirus disease 2019 (COVID-19). Many developing countries like Nepal faces various challenges and grab many future opportunities during and after establishment of molecular PCR laboratories throughout the country. This viewpoint describes the involvement of laboratory employees, development and adoption of new protocols or framework, deliberate partnership with national and international community is very efficient for the establishment of PCR laboratories. Beside this, continued alliance and nation leadership is crucial to generate a unified and sustainable PCR laboratory network in the country like Nepal. In future the established PCR laboratories can be utilized for the diagnosis of others pandemic diseases and can be used for multipurpose like in verification of infectious diseases; Oncology; Blood test; Genetic testing.

          Research Article Pages: 1 - 6

          Exploring Indian Spices as Promising Antimicrobial Agents

          Kirti Garg and Astha Giri

          Infectious diseases caused by pathogens, and food contamination caused by microorganisms, are compromising human health. The efficacies of antimicrobial agents and antibiotics, which are currently being used, have been weakened by microbial resistance, while antibiotic toxicity is a known challenge. This arises the need of natural antimicrobial agents. Spices and herbs have been long used for centuries, to enhance flavour and aroma of food, and for their antimicrobial and antioxidant activities. In this study, antimicrobial activity of aqueous and ethanolic extracts of five Indian spices i.e., Black pepper, Carom, Cinnamon, Clove and Cumin, was explored against Escherichia coli and Staphylococcus aureus, by agar dilution method and disk diffusion method. For agar dilution, aqueous and ethanolic extracts, with concentrations ranging from 0.5 mg/ml-8 mg/ml, were used. Whereas for disc diffusion method, varying concentrations of the ethanolic extracts (50%, 75% and 100%) were used. The results indicated an inhibitory effect on the growth of the microbes when using higher concentration of the extract. Clove’s bud showed the best antimicrobial effect amongst all the tested spices, having Minimum Inhibitory Concentration (MIC) less than 0.5 mg/ml for aqueous extract and 6 mg/ml for ethanolic extract against both bacteria. Amongst the tested spice extracts, Clove also had the biggest zone of inhibition i.e., 21 mm, against E. coli when using 50% ethanolic extract, while Black pepper had a zone of inhibition of 20 mm against S. aureus when using 100% ethanolic extract. It was also noted that the spice extracts, in general, were more effective against S. aureus than E. coli. Therefore, spices and particularly Clove and Black pepper extracts have great potential to be further tested and developed as novel safe antimicrobial agents

          Volume 5, Issue 2 (2021)

            Research Article Pages: 1 - 5

            Molecular Docking Study of Novel COVID-19 Protease with Low-Risk Terpenoids Compounds of Plants

            Neda Shaghaghi

            Background: Due to the reported high ability of virulence of COVID-19 in recent months, several studies have been conducted to discover and introduce COVID-19 antiviral drugs. The results of numerous studies have shown that protease inhibitors and compounds, which make up the major part of plant derivatives, especially terpenoids, can therefore be very effective in controlling virus-induced infection. The aim of this research is the bioinformatical study of COVID-19 inhibition by terpenoids of plant origin.

            Materials and methods: This is a descriptive-analytic study. In the present study, the structure of Terpene compounds were received from the databases such as PubChem and COVID-19 proteases were received Protein Data Bank (PDB). After that, molecular docking was performed by MVD (molegro virtual docker) software.

             Results: The results are identified to have inhibitory activities against novel COVID-19 protease. Of these compounds, Ginkgolide A has a stronger bond and high affinity with protease. The amount of connecting energy from high to less in order Ginkgolide A> DiThymoquinone>Noscapine>Salvinorin A>Forscolin>Bilobalide>Citral>Beta Selinene>Menthol. All of these compounds were linked to the intermediate flap that the software had predicted, and all of them were binded to 8 residues, and a total of 19 residues were binded.

            Conclusion: Finally, with due attention to the high effectiveness function of terpenoids, we can conclude that these compounds may be considered as effective COVID-19 antiprotease drugs. Also, due to the formation of blood clots in coronavirus infection, a number of these compounds, in addition to antiviral activity, have an effect on inhibiting coagulation.

            Research Article Pages: 1 - 6

            Investigation of Cepharanthine Binding with Viral Proteins Reveal its Potential Targets against Coronavirus

            Donghui Huo, Wenlin An, Huan Xu, Aixia Yan and Yigang Tong

            The outbreak of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 is becoming a worldwide problem. We previously reported that cepharanthine (CEP) demonstrated strong anti-coronavirus effects, however, the mechanism underlying CEP’s anti-coronavirus effects remains unknown. We herein performed Surface Plasmon Resonance (SPR) to investigate the biological influence of CEP on different proteins of SARS-CoV-2. Meanwhile, molecular docking study was used to screen the potential binding sites of CEP on the virus. The binding of CEP to the nsp13 helicase with a Kd of 3.806*10-6 M shows that helicase is a relatively strong possible target of CEP. Besides, CEP could bind to the viral main proteinase (3CLpro) that contributes to the intervention of polypeptide cleavage. We also compared the potential binding pockets and binding affinity on viral spike proteins (S1 and S2 subunits) at both open and closed states. Our study revealed that CEP exerts its anti-coronavirus effects at viral genomic RNA replication, transcription, translation and viral invasion levels, providing a theoretical basis for the development of CEP as a promising anti-coronavirus drug.

            Editorial Pages: 1 - 1

            WHO Renews Backing for Astrazeneca COVID

            George Sourvinos

            The World Health Organization gave sturdy backing to the AstraZeneca COVID-19 jab on Friday, urging countries to take care of the roll-out once reviewing reports of blood clots. Many European countries resumed AstraZeneca vaccinations on Friday once the European Medical Agency (EMA) likewise gave their inexperienced lightweight. "We perceive that individuals could have had considerations regarding the security of the Oxford-AstraZeneca immunogen. The question with any pharmaceutical or immunogen is whether or not the chance of taking it's bigger or but the chance of the malady it's meant to stop or treat. There's no question: COVID-19 could be a deadly malady and therefore the Oxford-AstraZeneca immunogen will forestall it. The obtainable information don't recommend any overall increase in natural action conditions following administration of the Oxford-AstraZeneca COVID-19 immunogen. We tend to urge countries to continue victimization this necessary immunogen. 'Tremendous potential' The WHO's world consultatory Committee on immunogen Safety (GACVS) met nearly associated It reviewed obtainable info and information on thromboembolic events (blood clots) and thrombopenia (low platelets) once vaccination with an AstraZeneca COVID-19 shot.

            Research Article Pages: 1 - 5

            Potential Docking Affinity of Three Approved Drugs Against SARS-CoV-2 for COVID-19 Treatment

            Venkata Sambasiva Rao Rachakulla and Hemanjali Devi Rachakulla

            Objectives: As the COVID-19 is rapidly spreading entire world and even though vaccines are distributing on emergency basis. There are enormous delays in supply chain due to huge gap between demand and production and also time factor for different phases of vaccination in the entire world. There is urgent need of alternate effective drug candidates from among the drugs already approved by FDA.

            Methods: We have studied the virtual interaction of crystal data structures of protein downloaded from protein data bank (PDB ID 7BRP) docked with corticosteroid drug candidates approved by FDA for other medical purposes which have less side effects. The results are analyzed in contrast some drugs candidates currently using for the treatment of COVID-19.

            Results: The binding energies in kilocalories/mole obtained from the docking of 7BRP protease with ligands under investigation Betamethasone Phosphate (-6.9), Fluticasone (-6.1) and Dexamethasone (-5.9) and also with currently using drug candidates Remdesivir (-6.5), Lopinavir (-6.0), Baceprivir (-5.7), Rabavirin (-6), Ritinovir (-5.3), Hydroxyquinoline (-5.0), Chloroquine (-4.7), Oseltamivir (-4.6), Favipiravir (-3.9).

            Discussion: The docking results suggest a higher binding affinity of the drug molecules under investigation against SARS-CoV-2 in contrast with other drug candidates currently being used for the treatment of COVID-19. We have analyzed bond interactions of protein-ligand from images in 10 modes of investigated drugs in contrast with Remdesivir and discussed the advantages of inhalation methods of drug fluticasone.

            Conclusion: From this study, it can be suggested that these carticosteroid drugs are promising candidates for antiviral treatment with high potential to fight against SARS-CoV-2 strain which needs further clinical studies. Especially, fluticasone an inhaler drug promising candidate which targets the infected lungs by COVID-1

            Research Article Pages: 1 - 7

            COVID-19 Pandemic and Bangladesh: A Review

            Mohammed Kamruzzaman

            Bangladesh, a developing country in the world. Like the other countries in the world it also hit by COVID-19 pandemic. This review article particularly analyzed some issues (e.g. Government measures, Economy, Mental health, Social issues and Vaccine) of Bangladesh related to COVID-19. Based on the published articles, news from print and electronic media, websites of different government and non-government organizations, available public data and some personal discussions are used to write this review paper. As the pandemic still on at the time of data been collected and no one knows when it’s going to stop, there can be addition of this paper in the future with updated data. It was a big challenge for Bangladesh to cope-up with the situation as a lower-middle-income economy with one of the world's densest populations. As winter is knocking the door here in Bangladesh, experts are assuming that the second wave will start very soon and the damage can be worst then the first wave. This paper may help the concerns to re-think what was there mistakes and how more organized way they can control the second wave and minimize the damage.

            Advances in Virology (2022)

              Research Article Pages: 1 - 10

              Ozone Preconditioning in Viral Disease

              James A Thorp*, KE Thorp, Elise Thorp and Deborah D Viglione

              DOI: 10.37421/2736-657X.06.S1.001

              Introduction: The purpose of this manuscript is to provide a narrative review of the literature and the basis of ozone therapy to treat viral illnesses including COVID-19 therapy.

              Methods: We performed a narrative review of 239 relevant publications and present new data not previously published from our group.

              Result: Ozone, a tri-atomic oxygen molecule is a natural substance made by the human white blood cells and metabolized into hydrogen peroxide and many lipo-peroxidases. Ozone is one of the most important modulators of the human immune system. Many investigators purport multiple potential mechanisms by which ozone treats a variety of viral and other illnesses at the atomic and cellular levels. While these mechanisms are operative, they represent passive events resulting from the ozone’s impartation of resonant energy to the human energetics’ fields. We present data demonstrating that the basis of most all human disease results from specific organ energetic deficiencies. Ozone may be one of the most potent preconditioning agents yet discovered in the human body. We discuss ozone dynamics, the vascular/blood connection, ozone preconditioning, and ozone therapy for specific viral diseases. Our review of the literature uncovered a spate of case reports describing beneficial outcomes with ozone treatment in diverse viral syndromes including Human Immunodeficiency Virus (HIV), Human Papillomavirus (HPV), hepatitis C, herpes zoster, ebola, and SARS-CoV-2. Additionally, we found in vitro studies describing inactivation of herpes and HIV by ozone treatment. We reviewed our successful use of ozone as an adjuvant and/or primary agent for the successful treatment of COVID-19. We report two cases of very successful use of ozone therapy in the maternal-fetal dyads in the severely infected/affected fetuses with CMV; this has never been reported in the medical literature.

              Conclusion: Ozone is an effective primary or adjuvant therapy for COVID-19 and for many other viral illnesses. Most all disease processes represent an energy deficient state and we have shown that the primary mechanism of ozone is to impart and restore energy deficiencies.

              Short Communication Pages: 1 - 3

              Anti-viral and Anti-inflammatory Effects of Camostat and Nafamostat on Influenza Virus and Coronavirus Infections in Human Airway Cells and the Mouse Lungs

              Mutsuo Yamaya* and Hidekazu Nishimura

              DOI: 10.37421/2736-657X.2022.S1.005

              Influenza viruses and coronaviruses cause several human diseases, such as bronchitis, bronchiolitis, and pneumonia, and exacerbate bronchial asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. Human airway epithelial cells infected with these viruses release progeny viruses and inflammatory cytokines, such as Interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α, partly through the activation of nuclear factor kappa B. Modulation of airway damage and inflammation may modulate viral infection-induced airway and lung diseases. Human tracheal and nasal epithelial cells express proteases, including Transmembrane Protease Serine S1 Member 2 (TMPRSS2), and the proteases activate influenza viruses and coronaviruses and the subsequent replication processes of these viruses. The protease inhibitors camostat and nafamostat reduced influenza virus and coronavirus replication and the amounts of cytokines released from human airway epithelial cells. Nafamostat also reduced the release of influenza virus in the lungs of mice. The development of clinically available protease inhibitors is required to treat patients infected with influenza virus or coronavirus.

              Research Article Pages: 1 - 7

              Protection from Omicron and other VOCs by Bivalent S-Trimer? COVID-19 Vaccine

              Danmei Su, Xinglin Li, Xueqin Huang, Cui He, Cheng Zeng, Qiang Wang, Wenchang Qin, Zhongquan Mu, Donna Ambrosino, George Siber, Ralf Clemens, Joshua G. Liang, Peng Liang, Nick Jackson and Rong Xu*

              DOI: 10.37421/2736-657X.06.2022.002

              The Omicron variant of SARS-COV-2 (GISAID GRA clade (B.1.1.529, BA.1 and BA.2)) is now the single dominant Variant Of Concern (VOC). The high number of mutations in the Omicron Spike (S) protein promotes humoral immunological escape. Although a third homologous boost with S, derived from the ancestral strain, was able to increase neutralizing antibody titers and breadth including to Omicron, the magnitude of virus neutralization could benefit from further optimization. Moreover, combining SARS-COV-2 strains as additional valences may address the current antigenicity range occupied by VOCs.

              Using Trimer-TagTM platform we have previously demonstrated phase 3 efficacy and safety of a prototypic vaccine SCB-2019 in the SPECTRA trial and have submitted applications for licensure. Here, we successfully generated a bivalent vaccine candidate including both Ancestor and Omicron variant S-proteins. Preclinical studies demonstrate this SARS-CoV-2 bivalent S-Trimer™ subunit vaccine elicits high titers of neutralizing antibodies against all VOCs, with markedly enhanced Omicron specific neutralizing antibody responses.

              Original Research Article Pages: 1 - 8

              Broadly Potent Neutralizing Bispecific Antibody against SARS-CoV-2

              Hui Zhang, Haohui Huang, Rong Li, Lu Zhang, Zhiwei Wang, Shide Liang, Jiaping Li, Junyou Chen, Huafei Su, Dandan Zheng, Ziqi Su, Li Wang, Xiong Mei, Shujun Pei, Shenghua Zhu, Chan Li, Yaochang Yuan, Haitao Yue, Yanqun Wang, Xiaobo Li, Cuihua Liu, Jinchen Yu, Hui Zhang, Shengfeng Li and Xianming Huang*

              DOI: 10.37421/2736-657X.06.2022.004

              The Omicron variant of Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) is threatening our global efforts fighting the COVID-19 pandemic. As the vast majority of current countermeasures against SARS-CoV-2 are completely or markedly losing their effectiveness, including most of the clinically approved neutralizing antibodies, better and more efficacious novel agents are urgently needed. We have developed a bispecific antibody, BAT2022, which bonds simultaneously with high affinity to two non-overlapping epitopes on the Receptor-Binding Domain (RBD), competitively blocks the binding of RBD to human Angiotensin-Converting Enzyme2 (ACE2) and potently neutralizes SARS-CoV-2 and all of the variants tested. The IC50 values in the pseudovirus assay for Omicron (BA.1) and Delta are 30 pM and 50 pM, respectively. A mouse model of SARS-CoV-2, BAT2022 showed strong prophylactic and therapeutic effects. Prophylactically, a single administration of BAT2022 completely protected mice from bodyweight loss, as compared with up to 20% loss of body weight in placebo- treated mice, reduced the lung viral titers to undetectable in all mice treated with BAT2022 either prophylactically or therapeutically, as compared with around 1 × 105 pfu/g lung tissue in placebo-treated mice. Overall, Bispecific Antibody BAT2022 showed potent binding and neutralizing activity across a variety of SARS- CoV-2 variants and could be an attractive weapon to combat the ongoing waves of the Omicron pandemic.

              Review Article Pages: 1 - 5

              Introduction of the STexS PCR Technique and the Advantages of Simultaneous Multi-target PCR Application

              Hyoung-Min Park, Jae Jong Kim, J Eugene Lee and Byoung Chul Park*

              DOI: 10.37421/2736-657X.06.S1.003

              Detecting and diagnosing small changes occurred by gene alteration via PCR is globally considered as an effective and precise method for handling various diseases. From the internal factors which change the normal body to develop disorders such as cancer to mutated external sources of infection that alters the intact human body, mainly bacteria and viruses. Among these, SARS-CoV-2 has emerged to be one of the most concerning threats to public health due to its rapid mutation. From the initial outbreak in 2019, research groups continuously identified various subtypes, some of which branched out as a novel variant of the original form that caused global health crisis among the population. While the standard PCR method of real-time quantitative reverse transcription is considered effective in detection and prevention, as more SARS-CoV-2 variants emerged, the overall process of identifying each variant one by one has deteriorated the standard procedure to be tiresome and time-consuming. To overcome the inefficiency, a novel PCR method using oligonucleotides (STexS) was introduced to significantly increase the specificity in detecting single nucleotide polymorphisms. Furthermore, the implementation of simultaneous multi-target PCR successfully isolated both Delta and Omicron variants within a single PCR trial, condensing the excessively long PCR procedure to be overall efficient and precise at the same time. The improvements will provide crucial insight in SARS-CoV-2 detection and diagnosis.

              Volume 5, Issue 5 (2021)

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