{"title":"siRNA-Inhibition of TIGAR Hypersensitizes Human Papillomavirus-Transformed Cells to Apoptosis Induced by Chemotherapy Drugs that Cause Oxidative Stress","authors":"Laçin Yapindi, B. Hernandez, R. Harrod","doi":"10.35248/1948-5964.21.13.223","DOIUrl":"https://doi.org/10.35248/1948-5964.21.13.223","url":null,"abstract":"The high-risk subtype Human Papillomaviruses (hrHPVs), including HPV16, HPV18, HPV31, HPV33, and HPV45, infect and oncogenically transform epithelial cells and cause squamous cell carcinomas and adenocarcinomas associated with the development of cervical cancer and subsets of vulvar, vaginal, penile, and anogenital cancers, as well as head-and-neck oropharyngeal carcinomas which often have poor clinical prognoses. Many cancers have been shown to contain elevated levels of the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR)-a glycolytic enzyme and antioxidant effector which frequently correlates with an aggressive tumor phenotype and serves as a determinant of therapy-resistance. We therefore tested whether siRNA-inhibition of TIGAR protein expression could sensitize HPV18-transformed HeLa cells to genotoxic chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and 4-hydroxycyclophosphamide) that induce oxidative stress and DNA-damage. Here we demonstrate that the siRNA-knockdown of TIGAR hypersensitized HeLa cells to low, otherwise sub-inhibitory concentrations of these drugs and markedly induced cellular apoptosis, as compared to a scrambled RNA (scrRNA) oligonucleotide negative control or a non-transformed immortalized human fibroblast cell-line, HFL1. Importantly, these findings suggest that therapeutically inhibiting TIGAR could hypersensitize hrHPV+ cervical tumor cells to low-dosage concentrations of chemotherapy drugs that induce oxidative DNA-damage, which could potentially lead to more favorable clinical outcomes by reducing the adverse side-effects of these anticancer medications and making them more tolerable for patients. Our studies have further shown that siRNA-inhibition of TIGAR sensitizes HPV18+ HeLa cells to apoptosis induced by 4-hydroxycyclophosphamide-a DNA-alkylating agent these cells were reported to have resistance to, alluding to another possible benefit of targeting TIGAR in combinatorial treatment strategies against virus-induced cancers.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86184010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coroless, effective ingredient isolated from traditional Chinese medicine for the prevention and treatment of Covid-19","authors":"Nie Leng, Liang Youdong, Yang Xinwei","doi":"10.37421/1948-5964.21.13.217","DOIUrl":"https://doi.org/10.37421/1948-5964.21.13.217","url":null,"abstract":"We believe that a good medicine for the prevention and treatment of Covid-19 requires three points: 1. Effectively inhibit the cells from being infected by Covid-19; 2. Quickly repair lung damage; 3. Non-toxic and harmless. Fortunately, from the treasure depot of Chinese traditional medicine, we found Kyllinga brevifolia Rottb, which is sufficient for three points and can be used for prevention, treatment and rehabilitation. Not only that, we have isolated the active ingredient of the Kyllinga brevifolia Rottb, named it Coroless, and verified that Coroless inhibits the Covid-19 from infecting cells through in vitro cell experiments.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88242891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Exploratory Study on COVID-19 and the Rights of Children Based on Keyword Network Analysis","authors":"Seoyeon Lee","doi":"10.21203/RS.3.RS-156498/V1","DOIUrl":"https://doi.org/10.21203/RS.3.RS-156498/V1","url":null,"abstract":"\u0000 COVID-19 has become a worldwide health crisis. Around March 2020, the entire country was shut down, including schools. This resulted in significant changes in the lives of children. In this study, the researcher conducted a keyword network analysis utilizing Ucinet ver 6.716 and NetDraw ver 2.173, after gathering the data using Textom in order to examine the current status of the rights of children in a COVID-19 pandemic. The findings of this study were that the degree centrality was higher with poverty, educational institutions, parents, teachers, income support, child care, child-rearing, caring, online classes, and child welfare, etc. Therefore, it can be said that there is an urgent need for the implementation of the respect of the rights of children all over the world in this COVID-19 pandemic.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83814623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sujan Rudra, Shuva Das, Md. Ehsanul Hoque, A. Kalam, Mohammad Arifur Rahman, Swagata Nandy Shizuka, T. Rahman
{"title":"Comorbidities of COVID-19 Patients with Low Cycle Threshold (Ct) Value of Nucleocapsid (N) Gene: An Application to Cluster-Based Logistic Model.","authors":"Sujan Rudra, Shuva Das, Md. Ehsanul Hoque, A. Kalam, Mohammad Arifur Rahman, Swagata Nandy Shizuka, T. Rahman","doi":"10.21203/RS.3.RS-147576/V2","DOIUrl":"https://doi.org/10.21203/RS.3.RS-147576/V2","url":null,"abstract":"\u0000 Background: Coronavirus disease 2019 (COVID-19) is a health crisis throughout the world. The widely used Real-time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) method is most capable of describing the patient’s condition. Comorbidities can make patients more critical.Methods: In this study, we shed light on the low cycle threshold (Ct) value of the N gene in the rRT-PCR test of the COVID-19 patients who had comorbidities, cure rate, and the needfulness of ICU (Intensive Care Unit) management. We had conducted the research in the Molecular Biology Laboratory of Chittagong Medical College between May and August 2020, then took the telephone interview with 300 positive patients who fulfilled the study criteria. We applied cluster-based logistic regression to analyze the data.Results: Low Ct value of the N gene found 1.324 times more in Type 2 DM patients and 1.871 times higher in hypertensive patients, and hospitalized patients are 2.480 times more vulnerable to shift in ICU.Conclusions: While infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) frequently causes severe diseases, suspected cases with comorbid conditions should go through the rRT-PCR as early as possible.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75769489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samir Samal, S. Mishra, E. Patra, Rajesh Kasimahanti
{"title":"A Questionnaire-Based Survey to Assess the Timing of Intubation in COVID-19 Pneumonia.","authors":"Samir Samal, S. Mishra, E. Patra, Rajesh Kasimahanti","doi":"10.21203/RS.3.RS-141346/V1","DOIUrl":"https://doi.org/10.21203/RS.3.RS-141346/V1","url":null,"abstract":"\u0000 BackgroundMany COVID19 pneumonia patients progress to Acute respiratory distress syndrome and end up in Intensive Care Units. Given that it is a novel viral infection, the progress of the disease, its management and associated outcomes are yet to be studied in detail. ARDS associated with COVID 19 is the same as before or different and the timing of intubation in such patients is a topic up for debate. This survey aimed to assess the opinion regarding management of COVID 19 ARDS and the timing of intubation in those patients.Methods292 clinicians including anesthesiologists, intensivists and others involved in managing COVID 19 ARDS patients at various centres were surveyed with web-based questionnaire cross sectionally within the time period of 10th June 2020 to 31st August 2020 after taking prior consent. Their responses were recorded and analyzed with statistical software IBM SPSS version 25.0.Results Among 292 included participants, 172 were intensivist, 84 were anesthesiologists and rest were others. Most of the intensivists (51.2%) had seen more than 100 COVID 19 severe ARDS patients. Around 82% of clinicians were agreed that COVID 19 ARDS was different from another form of ARDS. 67.1% of participants were agreed with patient induced self-inflicted injury could have happened in this disease. Likewise, around 91.8% of doctors involved in managing patients were believed that HFNC could be helpful if there were falling of saturation. 37% of participants were not agreed with early intubation, which may increase the risk of mortality and nosocomial infections.Conclusions and RelevanceThere was confusion in most doctors with intubation timing even if there was an indication for intubation. These confusions may be due to non-availability of specific recommendation regarding intubation in COVID 19 severe ARDS patients. However, most of the literature recommended for early intubation in these patients when indicated.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77581645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abundant transmission of Corona Virus Nsp2 RNA Topoisomerse I120F Mutants with Concurrence D614G Spike Protein Mutation in Australia","authors":"A. Chakraborty","doi":"10.35248/1948-5964.13.S16.001","DOIUrl":"https://doi.org/10.35248/1948-5964.13.S16.001","url":null,"abstract":"We previously predicted Nsp2 Corona virus protein as RNA topoisomerase through amino acid homology among Vibrio haemolytica DNA topoisomerase IA/IV as well as DNA primase, DNA gyrase and bi-subunit Trypanosoma brucei DNA topoisomerase IB. Many DNA topoisomerase I/III have RNA topoisomerase activity and such ubiquitous enzymes are conserved and involved in the regulation of replication and transcription. We have checked here mutational profile of Nsp2 RNA topoisomerase analyzing >10000 orf1a 4405 amino acid length Corona virus polyprotein. Mutant proteins were selected by BLAST search having 99.84% sequence similarity and 181-818aa portion Nsp2 protein (protein id. QIU82057) was analyzed using CLUSTAL Omega software. We found 26 different mutations where most changes were selected at Isoleucine and Alanine into Valine or Leucine into Phenylanaline pinpointing conserved nature of the Corona virus RNA topoisomerase. Major nonsense very abundant mutations were found at I120F (Isoleucine to Phenylalanine). Other important mutations were R27C, I198V, T85I, L410F, I559V and P583S. The I120F mutation was abundant in Australian isolates and its spread was seen in the Bangladesh and other countries like USA. We suggest that abundant I120F mutation of Nsp2 Topoisomerase may increase transmission of Corona virus by stabilizing RNA structure for efficient virus pakaging. Interestingly, such mutations were found in association of D614G mutation of Spike protein, known to >70% increase infectivity. On the contrary, all P583S Nsp2 mutants analyzed had no concurrence D614G spike protein mutation. Many silent mutations (5-7) were detected by genome wide analysis but no N501Y Spike protein mutation. This is first report that predicts a link of greater Corona virus transmission with Nsp2 protein I120F and spike protein D614G mutations.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75955743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reda Bzikha, Bouhmou Ayoub, Bzikha Ilham, S. Bouchnafati
{"title":"Remdesivir and Lopinavir/Ritonavir as Potential Drugs to Treat Corona Virus Disease 2019","authors":"Reda Bzikha, Bouhmou Ayoub, Bzikha Ilham, S. Bouchnafati","doi":"10.35248/1948-5964.20.S6.002","DOIUrl":"https://doi.org/10.35248/1948-5964.20.S6.002","url":null,"abstract":"Drugs that are efficacious against SARS-CoV-2 have yet to be established. Remdesivir and Lopinavir/ritonavir have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Remdesivir not only in vivo but also in vitro testing shows the inhibition of human coronavirus replication, including SARS-CoV aswell as Lopinavir/ritonavir that shows promising antiviral drug against SARS-CoV-2.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79281672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Some Retroviral Diseases of Humans and Animals: A Prospectus","authors":"Eltayb Abuelzein, M. Elamin, O. Ibrahim","doi":"10.35248/1948-5964.21.S21.002","DOIUrl":"https://doi.org/10.35248/1948-5964.21.S21.002","url":null,"abstract":"This prospectus, gives an account on five, highly epidemiologically significant, virus members of the family Retroviridae and the ailments they cause. These are the human (HIV-1 and HIV-2) and three animal retroviral diseases of veterinary importance viz. the Enzootic Bovine Leucosis Virus (EBLV); the Caprine Arthritis-Encephalitis Virus (CAEV) and the Equine Infectious Anemia Virus (EIAV). This is expected to give a dimension that can aid field veterinarians, especially in developing countries, to help in differential clinical diagnosis, between diseases that may have similar clinical picture to retrovirus infections in animals. This article also gives enlightenment on the history, classification, properties, ecology and the interesting peculiarities of the family Retroviridae.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80357336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Measles Virus as a Vector for the HPV Vaccine Development","authors":"N. Penta, Gaurav K Gupta, R. Glueck","doi":"10.35248/1948-5964.21.13.211","DOIUrl":"https://doi.org/10.35248/1948-5964.21.13.211","url":null,"abstract":"The Human Papilloma Virus (HPV) vaccine prevents infection with certain species of human papillomavirus associated with the development of cervical cancer, genital warts and some less common cancers. But, the development of vaccine that prevents HPV infection represents an important opportunity to prevent cervical cancer whilst a therapeutic immunization would be valuable in treating premalignant and malignant disease. Attenuated MV strains are highly efficient and safe vaccines, typically preventing recipients from Measles for their entire life. To benefit from these extraordinary vaccination properties in the present study MV cDNA plasmids have been constructed to produce precisely initiated and terminated MV anti-genome related to the Edmonston B vaccine strains. These transgenes were expressed at different levels, according to their genomic position and were stably maintained over many viral generations. The ability to construct new recombinant and chimeric MVs opens the prospect to develop new vaccines based on MV. In an effort to generate an inexpensive candidate HPV vaccine with improved prophylactic potential, a MV vector based on Berna-commercial Measles vaccine strain (Edmonston- Zagreb) inducing against HPV was developed.","PeriodicalId":15020,"journal":{"name":"Journal of Antivirals & Antiretrovirals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90819316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}