scholarly journals Anti-HCV antiviral therapies as an alternative for the treatment of Covid-19

2020 ◽  
Vol 9 (10) ◽  
pp. e9489109406
Author(s):  
Giuliene Rocha de Medeiros ◽  
Isabela Cristina Cordeiro Farias ◽  
João Victor Cordeiro Farias ◽  
Penelopy Rodrigues de Macedo
Keyword(s):  
Clinical Trials ◽  
Hepatitis C ◽  
Clinical Results ◽  
Antiviral Therapies ◽  
The World ◽  
Qualitative Nature ◽  
Catalytic Mechanisms ◽  
Type Studies ◽  
The Moment ◽  
Potential Inhibitors

The current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread alarmingly around the world at a significantly faster speed than previous coronaviral outbreaks. Due to the lack of a vaccine at the moment, an early antiviral intervention can prevent the spread of the disease worldwide and improve the clinical results of infected patients. The SARS-CoV-2 virus and the Hepatitis C virus (HCV) have a similar structure, replication, and catalytic mechanisms, therefore, several studies have considered the potential for antiviral activity of anti-HCV drugs such as remdesivir, simeprevir, sofosbuvir, and daclatasvir against SARS-CoV-2. Therefore, the present study aims to evaluate and discuss the antivirals already available against HCV, which have also been shown to be potential inhibitors of SARS-CoV-2 replication. The study was based on a literature review, of a qualitative nature and an exploratory type. Studies with anti-HCV drugs are promising and are already considered to start clinical trials in patients infected with the new coronavirus, having been observed as inhibitors of SARS-CoV-2 viral replication. Thus, the present study brings a pharmaco-clinical review on antivirals remdesivir, simeprevir, sofosbuvir, and daclatasvir, considering the main studies carried out to date in the treatment for Covid-19.

scholarly journals Safety and efficacy of RNA vaccines: State of the art

2021 ◽  
Vol 23 (5) ◽  
pp. 1017-1030
Author(s):  
A. V. Blagov ◽  
A. A. Bukaeva ◽  
V. V. Makarov ◽  
Z. V. Bochkaeva
Keyword(s):  
Clinical Trials ◽  
Ebola Virus ◽  
Viral Infections ◽  
Phase Iii ◽  
Protective Properties ◽  
Market Launch ◽  
The World ◽  
Mass Immunization ◽  
First Results ◽  
The Moment

This review describes principles of action and the method of delivery of mRNA molecules into cells, as well as some of developed RNA vaccines and the results obtained in their study, though they have not been authorized for use yet. In addition, the review discusses efficacy and safety proved for RNA vaccines registered for COVID-19 prevention at the time of writing. The development, clinical trials and market launch of RNA vaccines for mass immunization in a few months can be considered one of the major breakthroughs in pharmacology over the past year. Despite of all seemingly indisputable advantages, none of RNA vaccines had reached Phase III of clinical trials since the moment of its discovery in 1993 until last year. The first experience of the successful use of mRNA vaccines was back in the 90s of the last century, when vaccination of mice with liposomes encoding an antigen-encoding mRNA was found to initiate specific immune response in mice. However, in these years, the method did not find application, due to the toxicity of lipids used. Subsequently, a large number of attempts have been made to develop vaccines against other viral infections, including Zika virus, Dengue virus, Ebola virus, cytomegalovirus, influenza virus and others. Despite the importance for preventing the spread of these diseases, the development of a vaccine preparation is a rather lengthy process, and final success is not guaranteed. However, the COVID-19 pandemic has become speeded the development of mRNA vaccines up.At the time of writing the review, two mRNA-based vaccines have been registered only in the world, both, BNT162b2 and mRNA-1273, were against COVID-19. Their effectiveness and safety are still actively studied. Moreover, it took less than a year for new strains of SARS-CoV-2 to appear, and the efficiency of vaccines against them was found to be lower than against the reference pathogen variant. Considering that the three new strains of SARS-CoV-2, “British”, “African” and “Brazilian”, are rapidly spreading in the world, the first results of efficiency evaluation of vaccines against them have already been published. One may expect that, considering mutations in these strains, the BNT162b2 and mRNA-1273 vaccines will remain effective against the “British” strain, but their protective properties are greatly weakened against the “African” variant.

scholarly journals Vaccine Development against COVID-19: Study from Pre-Clinical Phases to Clinical Trials and Global Use

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 836
Author(s):  
Sagheer Ahmed ◽  
Saeed Khan ◽  
Imran Imran ◽  
Fadwa Al Mughairbi ◽  
Fahad Sultan Sheikh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Clinical Investigation ◽  
World Health ◽  
Phase 3 ◽  
Global Demand ◽  
The World ◽  
Advanced Stages ◽  
The Moment ◽  
Health Organization

As per the World Health Organization (WHO), more than 288 vaccines against COVID-19 are being developed, with an estimated 184 being presently investigated in the pre-clinical phases, while 104 of these vaccine candidates are at various stages of clinical trials. Twelve of these are in the advanced stages of clinical investigation, and promising results in the phase 3 trials have already paved the way for their regulatory approval and subsequent dissemination for global use. Preliminary and interim results of some of these candidate vaccines are being analyzed for public dissemination. Some of these vaccines have already been rolled out to immunize not only the highest risk individuals but also the general population in several countries. Once their safety and efficacy are established, the next limiting step would be their mass manufacturing by the pharmaceutical companies to fulfill the global demand. The challenge of manufacturing billions of doses of high-quality vaccines is under-appreciated at the moment. A massive vaccination drive would be needed to protect people of all ages. The timely and coordinated execution of the vaccination effort would require unprecedented coordination at the national and international levels for generating funds to purchase the required doses of vaccines, fair distribution of doses and managing the mechanics of delivering vaccines throughout the world.

scholarly journals Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease

2021 ◽  
Vol 12 ◽  
Author(s):  
Luca Pinzi ◽  
Annachiara Tinivella ◽  
Fabiana Caporuscio ◽  
Giulio Rastelli
Keyword(s):  
Clinical Trials ◽  
Antiviral Activity ◽  
Inhibitory Activity ◽  
Therapeutic Indication ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Main Protease ◽  
The World ◽  
Potential Inhibitors ◽  
Late Stages

The outbreak of a new coronavirus (SARS-CoV-2), which is responsible for the COVID-19 disease and is spreading rapidly around the world, urgently requires effective therapeutic treatments. In this context, drug repurposing represents a valuable strategy, as it enables accelerating the identification of drug candidates with already known safety profiles, possibly aiding in the late stages of clinical evaluation. Moreover, therapeutic treatments based on drugs with beneficial multi-target activities (polypharmacology) may show an increased antiviral activity or help to counteract severe complications concurrently affecting COVID-19 patients. In this study, we present the results of a computational drug repurposing campaign that aimed at identifying potential inhibitors of the main protease (Mpro) of the SARS-CoV-2. The performedin silicoscreening allowed the identification of 22 candidates with putative SARS-CoV-2 Mproinhibitory activity. Interestingly, some of the identified compounds have recently entered clinical trials for COVID-19 treatment, albeit not being assayed for their SARS-CoV-2 antiviral activity. Some candidates present a polypharmacology profile that may be beneficial for COVID-19 treatment and, to the best of our knowledge, have never been considered in clinical trials. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

Natural Potential Inhibitors for Covid 19 – An Insilico Approach

2021 ◽  
pp. 4913-4919
Author(s):  
A. Anto Arockia Raj ◽  
Vinnarasi J.
Keyword(s):  
Molecular Docking ◽  
Hepatitis C ◽  
Antiviral Effect ◽  
Antiviral Drugs ◽  
Food Additive ◽  
Potential Drug ◽  
Highly Pathogenic ◽  
The World ◽  
Human Coronaviruses ◽  
Potential Inhibitors

In 2019 severe acute respiratory syndrome (SARS) - associated with coronavirus is a new highly pathogenic human coronaviruses that emerged in china and has quickly spread all over the world. The mortality rate is about 26% globally. This has resulted in an urgent need to identify antiviral drugs that are active against SARS-Covid -19. Several compounds extracted from natural product and herbs exhibit antiviral activity. In the present study, eight compounds from natural products and five antiviral drugs have selected and docked against SARS-CoV-2. Curcuminoid are chief constituent of turmeric, has been used as a food additive and herbal increment due to its potential medicinal behavior. Curcumin has shown better antiviral effect against dengue, hepatitis C, zika and chikungunya viruses earlier. The molecular docking for exploring the binding abilities between naturally obtained known compounds comparable with Oseltamivir, Remdesivir, hydroxychloroquine, Zanamivir and Ribavirin against SARS-CoV-2, whose results may be used to design potential drug to meet out the need of the hour. The results showed that bismethoxycurcumin, demethoxycurcumin and gedunin have comparable high binding pose energies against SARS-CoV-2. We anticipate that these molecules may lead to the design or discovery of new effective actions for SARS-CoV-2.

scholarly journals Drug repurposing and polypharmacology to fight SARS-CoV-2 through the inhibition of the main protease

2020 ◽  
Author(s):  
Luca Pinzi ◽  
Annachiara Tinivella ◽  
Fabiana Caporuscio ◽  
Giulio Rastelli
Keyword(s):  
Clinical Trials ◽  
Antiviral Activity ◽  
Therapeutic Indication ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Selection Of

Abstract Therapeutic options are urgently needed to fight the outbreak of a novel coronavirus (SARS-CoV-2), which causes the COVID-19 disease and is spreading rapidly around the world. Drug repurposing can significantly accelerate the identification of drug candidates suitable for clinical evaluation. Moreover, polypharmacological effects may increase antiviral activity and/or counteract severe complications concurrently affecting COVID-19 patients. Herein, we present the results of a computational drug repurposing campaign in search of potential inhibitors of the main protease of SARS-CoV-2. The screening allowed the selection of 22 promising drugs. Some of them have already entered clinical trials, but the vast majority of the identified compounds are new and have never been considered before. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

Hepatitis C Virus Infection: A Brief Review

JMS SKIMS ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 3-15
Author(s):  
Saleem Kamili ◽  
Hisham Qadri
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Basic Research ◽  
World Health ◽  
Hepatitis C Virus Infection ◽  
Poor Countries ◽  
Diagnostic Assays ◽  
Antiviral Therapies ◽  
Highly Sensitive ◽  
Resource Poor

Hepatitis C, caused by hepatitis C virus (HCV) was originally described as parenterally transmitted non-A non-B hepatitis. Since its discovery in 1989, the field of HCV research has become a shining example of successful translation of basic research wherein in a short of span of just 30 years the virus was discovered, highly sensitive and specific diagnostic assays were developed, epidemiology and clinical characteristics of the disease were well defined and now with the availability of highly efficacious antiviral therapies many countries are already on their way to achieving World Health Organization’s (WHO) elimination targets of hepatitis C by 2030.  However, much work needs to be done to eliminate hepatitis C especially in resource poor countries. Most recent data show an estimated 71 million people are currently infected with HCV worldwide and approximately 400,000 people die each year from causes related to HCV. Of these estimates, more than 13 million HCV infected persons are in India and Pakistan (Figure 1). Despite the availability of a cure for hepatitis C, only 20% of those infected patients have been diagnosed (1). In order to achieve the WHO targets of hepatitis C elimination, concerted efforts will have to made to make affordable and reliable diagnostics available worldwide.

PINGVINAS IR PROTĖJAS. Įsivaizdavimas kaip kitybė manyje

2007 ◽  
Vol 4 ◽  
pp. 21-37
Author(s):  
Kristupas Sabolius
Keyword(s):  
Fight Club ◽  
The World ◽  
The Moment ◽  
Hollywood Movie

Kitybės klausimas dažniausiai kyla iš ego santykio su kitais arba su pasauliu. Šiame straipsnyje daroma prielaida, kad įsivaizdavimo funkcija ištirpdo subjektą ir jame pačiame atveria intersubjektyvią perspektyvą. Šiuo tikslu sugretinami Sartre’o, Husserlio bei Merleau-Ponty įsivaizdavimo funkcijos tyrimai, kuriuose išryškėja vaizdo kaip iš ego centro išslystančios ribos statusas, ir Holivudo filmo „Kovos klubas“ siužetas. Viename iš šios juostos epizodų pasirodantis pingvinas žymi egologinės schizmos akimirką ir tampa fantazijos apsireiškimu ir įsikūnijimu.Išgryninus žaidybinį, savarankišką ir multiformišką charakterį, galime konstantuoti, kad įsivaizdavimas, jei kalbėtume Kanto terminais, yra ne papildanti tarpinė funkcija, bet transcendentalinio subjekto genezėje atlieka paradoksalų „svetimos vidujybės“ arba „vidinės svetimybės“ vaidmenį. Vaizduotė yra katalizatoriaus, kuris, likdamas šalia, įgalina transcendentalinių formų išsikristalizavimą.Pagrindiniai žodžiai: vaizduotė, įsivaizdavimas, fantazija, ego, kitybė, sąmonė.PENGUIN AND PROTEUSImagination as Otherness in meKristupas Sabolius SummaryThe question of Otherness is usually taken into account while discussing the Ego’s relation with Others as well as with the World. This article is based on the premises that the function of phantasy melts the subjectivity, revealing the perspective of intersubjectivity within it. On this purpose Sartre’s, Husserl’s and Merleau-Ponty’s researches on the function of imagination, which elucidate the image as the boundary slipping from the centre of Ego, are compared to the story of Hollywood’ movie „Fight Club“. The penguin, which appears in one of the episodes, registers the moment of egological schism, thus becoming the revelation and incarnation of phantasy. While the playful, autonomous and multiform character of imaginary is cleared out, we can ascertain, speaking in Kantian terms, that it has not a complementary or intermediary function, but, in the genesis of transcendental subject, plays the paradoxical role of „allien innerness“ or „inner alienity“. Thought remaining always beside, imagination is a catalyzer which enables crystallization of transcendental forms.Keywords: imagination, imaginary, phantasy, ego, otherness, consciousness.

Erfahrung ohne Erfahrenden

2009 ◽  
Vol 2009 (1) ◽  
pp. 61-78
Author(s):  
Petr Kouba
Keyword(s):  
Phenomenological Approach ◽  
Work Of Art ◽  
New Beginning ◽  
Individual Structure ◽  
The World ◽  
Il Y A ◽  
Individual Existence ◽  
The Moment ◽  
The Individual ◽  
Intentional Structure

This article examines the limits of Heidegger’s ontological description of emotionality from the period of Sein und Zeit and Die Grundbegriffe der Metaphysik along the lines outlined by Lévinas in his early work De l’existence à l’existant. On the basis of the Lévinassian concept of “il y a”, we attempt to map the sphere of the impersonal existence situated out of the structured context of the world. However the worldless facticity without individuality marks the limits of the phenomenological approach to human existence and its emotionality, it also opens a new view on the beginning and ending of the individual existence. The whole structure of the individual existence in its contingency and finitude appears here in a new light, which applies also to the temporal conditions of existence. Yet, this is not to say that Heidegger should be simply replaced by Lévinas. As shows an examination of the work of art, to which brings us our reading of Moravia’s literary exposition of boredom (the phenomenon closely examined in Die Grundbegriffe der Metaphysik), the view on the work of art that is entirely based on the anonymous and worldless facticity of il y a must be extended and complemented by the moment in which a new world and a new individual structure of experience are being born. To comprehend the dynamism of the work of art in its fullness, it is necessary to see it not only as an ending of the world and the correlative intentional structure of the individual existence, but also as their new beginning.

Differenzierungen im Begriff, Gegenwart‘ bei Husserl und Merleau-Ponty

2017 ◽  
Vol 2017 (1) ◽  
pp. 39-54
Author(s):  
Jörg Zimmer
Keyword(s):  
Modern Philosophy ◽  
The Body ◽  
Fundamental Concept ◽  
Phenomenological Description ◽  
Philosophy Of Time ◽  
Phenomenology Of Perception ◽  
The World ◽  
Classical Philosophy ◽  
The Moment ◽  
Empty Time

In classical philosophy of time, present time mainly has been considered in its fleetingness: it is transition, in the Platonic meaning of the sudden or in the Aristotelian sense of discreet moment and isolated intensity that escapes possible perception. Through the idea of subjective constitution of time, Husserl’s phenomenology tries to spread the moment. He transcends the idea of linear and empty time in modern philosophy. Phenomenological description of time experience analyses the filled character of the moment that can be detained in the performance of consciousness. As a consequence of the temporality of consciousness, he nevertheless remains in the temporal conception of presence. The phenomenology of Merleau-Ponty, however, is able to grasp the spacial meaning of presence. In his perspective of a phenomenology of perception, presence can be understood as a space surrounding the body, as a field of present things given in perception. Merleau-Ponty recovers the ancient sense of ‘praesentia’ as a fundamental concept of being in the world.

Anxious Breath

Screen Bodies ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 111-128
Author(s):  
Lara Bochmann ◽  
Erin Hampson
Keyword(s):  
Public Space ◽  
Self Determination ◽  
Short Film ◽  
Affective States ◽  
The World ◽  
In Trans ◽  
The Moment ◽  
Everyday Task

This article is a theoretical, audiovisual, and personal exploration of being a trans and non-binary person and the challenges this position produces at the moment of entering the outside world. Getting ready to enter public space is a seemingly mundane everyday task. However, in the context of a world that continuously fails or refuses to recognize trans and non-binary people, the literal act of stepping outside can mean to move from a figurative state of self-determination to one of imposition. We produced a short film project called Step Out to delve into issues of vulnerability and recognition that surface throughout experiences of crossing the threshold into public space. It explores the acts performed as preparation to face the world, and invokes the emotions this can conquer in trans and non-binary people. Breathing is the leading metaphor in the film, indicating existence and resistance simultaneously. The article concludes with a discussion of affective states and considers them, along with failed recognition, through the lens of Lauren Berlant’s concept of “cruel optimism.”

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