scholarly journals Understanding the clinical utility of favipiravir (T-705) in coronavirus disease of 2019: a review

2021 ◽  
Vol 8 ◽  
pp. 204993612110630
Author(s):  
Kritika Srinivasan ◽  
Mana Rao
Keyword(s):  
Clinical Trials ◽  
Clinical Utility ◽  
Viral Infections ◽  
Vaccine Development ◽  
Rna Replication ◽  
Therapeutic Agents ◽  
Viral Rna ◽  
Widespread Application ◽  
Global Pandemic

The coronavirus disease of 2019 (COVID-19) has caused significant morbidity and mortality among infected individuals across the world. High transmissibility rate of the causative virus – Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) – has led to immense strain and bottlenecking of the health care system. While noteworthy advances in vaccine development have been made amid the current global pandemic, most therapeutic agents are repurposed from use in other viral infections and are being evaluated for efficacy in COVID-19. Favipiravir, an orally administered drug originally developed in Japan against emerging influenza viral strains, has been shown to have widespread application and safety across multiple ribonucleic acid (RNA) viral infections. With a strong affinity toward the viral RNA-dependent RNA polymerase (RdRp), favipiravir could be a promising therapy against SARS-CoV-2, by targeting downstream viral RNA replication. Initial trials for usage in COVID-19 have suggested that favipiravir administration during initial infection stages, in individuals with mild to moderate infection, has a strong potential to improve clinical outcomes. However, additional well-designed clinical trials are required to closely examine ideal timing of drug administration, dosage, and duration, to assess the role of favipiravir in COVID-19 therapy. This review provides evidence-based insights and throws light on the current clinical trials examining the efficacy of favipiravir in tackling COVID-19, including its mechanism, pharmacodynamics, and pharmacokinetics.

scholarly journals COVID-19: Role of Nutrition and Supplementation

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 976
Author(s):  
Fiorenzo Moscatelli ◽  
Francesco Sessa ◽  
Anna Valenzano ◽  
Rita Polito ◽  
Vincenzo Monda ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Viral Infections ◽  
Overweight And Obesity ◽  
Shortness Of Breath ◽  
Nutritional Interventions ◽  
The World ◽  
Diet Regimen ◽  
Specific Diet

At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2–3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.

Oral probiotics in women's health: experimental evidence and results from clinical trials

2021 ◽  
Vol 20 (2) ◽  
pp. 102-109
Author(s):  
E.V. Shikh ◽  
◽  
A.A. Makhova ◽  
S.S. Sharonova ◽  
◽  
...  
Keyword(s):  
Clinical Trials ◽  
Gestational Diabetes ◽  
Polycystic Ovary Syndrome ◽  
Viral Infections ◽  
Polycystic Ovary ◽  
Gynecological Cancer ◽  
Ovary Syndrome ◽  
Treatment Regimens ◽  
Probiotic Lactobacilli

The review presents data from experimental research of the anti-inflammatory activity of Lactobacillus paracasei, L. plantarum, L. rhamnosus, the antitumor activity of L. rhamnosus GG and GR-1, L. gasseri, L. crispatus. The prospect of using probiotics in cancer treatment regimens with the aim to increase the tolerability of treatment was considered. The data confirming the ability of probiotic lactobacilli (L. reuteri and L. rhamnosus) to enhance barrier functions of endometrial epithelial cells in response to human papillomavirus-1 were presented. The perspectives of using microbiota modulation to prevent and/or protect the reproductive system against infection were discussed. The data of clinical trials using multi-strain probiotics containing Lactobacillus and Bifidobacterium in women with gestational diabetes were analyzed. A hypothesis on the role of microbiota in the pathogenesis of polycystic ovary syndrome (PCOS) was presented. Research results suggest that the use of probiotics can increase fertility in PCOS. Key words: viral infections, gestational diabetes mellitus, gynecological cancer, oral probiotics, polycystic ovary syndrome, Lactobacillus spp.

Role of Cellular Structures in Viral RNA Replication

2014 ◽  
pp. 247-253 ◽  
Author(s):  
Denise Egger ◽  
Rainer Gosert ◽  
Kurt Bienz
Keyword(s):  
Rna Replication ◽  
Viral Rna ◽  
Cellular Structures

Cross-neutralization antibodies against SARS-CoV-2 and RBD mutations from convalescent patient antibody libraries

2020 ◽  
Author(s):  
Yan Lou ◽  
Wenxiang Zhao ◽  
Haitao Wei ◽  
Min Chu ◽  
Ruihua Chao ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Receptor Binding Domain ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Antibodies ◽  
Global Pandemic ◽  
Antibody Libraries ◽  
Cross Neutralization

AbstractThe emergence of coronavirus disease 2019 (COVID-19) pandemic led to an urgent need to develop therapeutic interventions. Among them, neutralizing antibodies play crucial roles for preventing viral infections and contribute to resolution of infection. Here, we describe the generation of antibody libraries from 17 different COVID-19 recovered patients and screening of neutralizing antibodies to SARS-CoV-2. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Then the positive clones were sequenced and reconstituted into whole human IgG for epitope binning assays. After that, all 19 IgG were classified into 6 different epitope groups or Bins. Although all these antibodies were shown to have ability to bind RBD, the antibodies in Bin2 have more superiority to inhibit the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 can also strongly bind with mutant RBDs (W463R, R408I, N354D, V367F and N354D/D364Y) derived from SARS-CoV-2 strain with increased infectivity, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, these neutralizing antibodies strongly restrict the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, these antibodies can even block the entry of live SARS-CoV-2 into cells at only 12.5 nM. These results suggest that these neutralizing human antibodies from the patient-derived antibody libraries have the potential to become therapeutic agents against SARS-CoV-2 and its mutants in this global pandemic.

scholarly journals The Role of Animal Models in Evaluating Reasonable Safety and Efficacy for Human Trials of Cell-Based Interventions for Neurologic Conditions

2008 ◽  
Vol 29 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Alan Regenberg ◽  
Debra JH Mathews ◽  
David M Blass ◽  
Hilary Bok ◽  
Joseph T Coyle ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Regenerative Medicine ◽  
Therapeutic Agents ◽  
Preclinical Studies ◽  
Safety And Efficacy ◽  
Proper Role ◽  
New Treatments ◽  
Gathering Data

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

scholarly journals Role of high dose IV vitamin C and zinc in coronavirus

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Arooj Fatima ◽  
Muhammad Usman Ali Khan ◽  
Mehkaar Najeeb ◽  
Muhammad Yasoob Ali Khan ◽  
Faiz Ul Haq
Keyword(s):  
Vitamin C ◽  
Viral Infections ◽  
Physiological Activity ◽  
Symptomatic Treatment ◽  
Primary Treatment ◽  
High Dose ◽  
Global Pandemic ◽  
The Common ◽  
Taste And Smell

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome- related coronavirus 2 (SARS-CoV- 2), is now considered as an ongoing global pandemic. Common symptoms include pyrexia, cough, dyspnea, fatigue, sore throat, and loss of sense of taste and smell. Complications that can result from more severe insult on lung tissue is pneumonia and acute respiratory distress syndrome (ARDS), which can further lead to septic shock. It is also not uncommon to find neurological symptoms in patients suffering from COVID-19. The primary treatment for COVID-19 is symptomatic treatment and supportive care. As there is no known vaccination and antiviral therapy for this disease, there is a desperate need to find an alternative to control and stop the spread of disease. Maintaining adequate micronutrient balance might enhance the immunity and protect from viral infections as well. Vitamin C and zinc helps in improving symptoms and shortening the duration of the common cold. Vitamin C (L-ascorbic acid) possesses pleiotropic physiological activity. High dose Vitamin C has shown to be effective against the common flu, rhinovirus, avian virus, chikungunya, Zika, ARDS, and influenza, and there is evidence that supports the protective effect of high dose IV vitamin C during sepsis-induced ARDS due to COVID-19. Zinc has a profound impact on the replication of viruses. Increasing intracellular zinc concentration along with pyrithione (zinc ionophore) has been shown to impair the replication of several RNA viruses efficiently, including poliovirus, influenza virus and several picornaviruses. A combination of zinc and can also inhibit the replication of SARS-coronavirus in cell culture.

scholarly journals Current Clinical Trials and Vaccine Development Strategies for Corona Virus Disease (COVID-19)

2020 ◽  
Vol 14 (suppl 1) ◽  
pp. 979-988
Author(s):  
Abhi Bhadra ◽  
Shweta Singh ◽  
Shaswat Chandrakar ◽  
Vanshika Kumar ◽  
Sakshi Sankhla ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Therapy ◽  
Mesenchymal Stromal Cell ◽  
Vaccine Development ◽  
Virus Disease ◽  
Therapeutic Agents ◽  
Diagnostic Methods ◽  
Global Epidemic ◽  
Pharmaceutical Industries ◽  
Pharmaceutical Interventions

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached global epidemic status claiming more than 319K lives and affecting more than 4.81M people and counting worldwide. Considering the severity of the situation and low recovery rate many research institutions and pharmaceutical industries are rushing to learn more about this new virus and the morbid physiology of this disease with effective diagnostic methods, therapeutic agents and vaccines. Various approaches are highlighted for comparing the possible treatment methods available for COVID-19 some of which are BCG vaccination on COVID-19 and Non-pharmaceutical interventions, drug based clinical trials of Hydroxychloroquine-Azithromycin, chloroquine, lopinavir/ritonavir, ChAdOx1 nCoV-19, Remdesivir, Stem Cell therapy and mesenchymal stromal cell therapy, etc.

scholarly journals Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments

2021 ◽  
Vol 12 ◽  
Author(s):  
Sangiliyandi Gurunathan ◽  
Min Hee Kang ◽  
Jin-Hoi Kim
Keyword(s):  
Vaccine Development ◽  
Antiviral Drug ◽  
Treatment Strategies ◽  
Antiviral Drugs ◽  
Therapeutic Benefits ◽  
Global Pandemic ◽  
Lung Injuries ◽  
Infected Cells ◽  
Intercellular Spread

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized, lipid bilayer-enclosed structures, share structural similarities with viruses secreted from all types of cells, including those lining the respiratory tract. Importantly, the interplay between exosomes and viruses could be potentially exploited for antiviral drug and vaccine development. Exosomes are produced by virus-infected cells and play crucial roles in mediating communication between infected and uninfected cells. SARS-CoV-2 modulates the production and composition of exosomes, and can exploit exosome formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Exosomes have been exploited for therapeutic benefits in patients afflicted with various diseases including COVID-19. Furthermore, the administration of exosomes loaded with immunomodulatory cargo in combination with antiviral drugs represents a novel intervention for the treatment of diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents. Mesenchymal stem cell derived exosomes reduces the cytokine storm and reverse the inhibition of host anti-viral defenses associated with COVID-19 and also enhances mitochondrial function repair lung injuries. We discuss the role of exosomes in relation to transmission, infection, diagnosis, treatment, therapeutics, drug delivery, and vaccines, and present some future perspectives regarding their use for combating COVID-19.

scholarly journals Poliovirus cre(2C)-Dependent Synthesis of VPgpUpU Is Required for Positive- but Not Negative-Strand RNA Synthesis

2003 ◽  
Vol 77 (9) ◽  
pp. 5136-5144 ◽  
Author(s):  
B. Joan Morasco ◽  
Nidhi Sharma ◽  
Jessica Parilla ◽  
James B. Flanegan
Keyword(s):  
Rna Synthesis ◽  
Rna Replication ◽  
Viral Rna ◽  
Positive Strand ◽  
Negative Strand ◽  
Replication Model ◽  
Covalently Linked

ABSTRACT The cre(2C) hairpin is a cis-acting replication element in poliovirus RNA and serves as a template for the synthesis of VPgpUpU. We investigated the role of the cre(2C) hairpin on VPgpUpU synthesis and viral RNA replication in preinitiation RNA replication complexes isolated from HeLa S10 translation-RNA replication reactions. cre(2C) hairpin mutations that block VPgpUpU synthesis in reconstituted assays with purified VPg and poliovirus polymerase were also found to completely inhibit VPgpUpU synthesis in preinitiation replication complexes. Surprisingly, blocking VPgpUpU synthesis by mutating the cre(2C) hairpin had no significant effect on negative-strand synthesis but completely inhibited positive-strand synthesis. Negative-strand RNA synthesized in these reactions immunoprecipitated with anti-VPg antibody and demonstrated that it was covalently linked to VPg. This indicated that VPg was used to initiate negative-strand RNA synthesis, although the cre(2C)-dependent synthesis of VPgpUpU was inhibited. Based on these results, we concluded that the cre(2C)-dependent synthesis of VPgpUpU was required for positive- but not negative-strand RNA synthesis. These findings suggest a replication model in which negative-strand synthesis initiates with VPg uridylylated in the 3′ poly(A) tail in virion RNA and positive-strand synthesis initiates with VPgpUpU synthesized on the cre(2C) hairpin. The pool of excess VPgpUpU synthesized on the cre(2C) hairpin should support high levels of positive-strand synthesis and thereby promote the asymmetric replication of poliovirus RNA.

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