scholarly journals The LIFE CYCLE OF COVID-19 STAGES AND TREATMENT

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Ripu Daman M. Singh ◽  
Nida Malim ◽  
Aves Raza Khan ◽  
Huda Khan ◽  
Nauman Khatib ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Life Cycle ◽  
Severe Acute Respiratory Syndrome ◽  
Late Phase ◽  
Antiviral Drug ◽  
Cytokine Storm ◽  
Clinical Recovery ◽  
The World ◽  
Autoimmune Conditions ◽  
Viral Outbreak

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)bat viruses, therefore bats could be the possible primary reservoir , which emerged in Wuhan, China and spread around the world. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. We also discuss the approaches for  therapeutic combinations to cope with this viral outbreak. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients.

scholarly journals Structure, transmission, diagnostic symptoms, host and entry mechanism of covid-19: A review

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Prashant Swapnil ◽  
Mukesh Meena ◽  
Tansukh Barupal ◽  
Yashwant Sompura ◽  
Deepa Hada
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Antiviral Drug ◽  
Genomic Analysis ◽  
Clinical Recovery ◽  
Human Contact ◽  
The World ◽  
Diagnostic Symptoms ◽  
Viral Outbreak ◽  
Entry Mechanism

Abstract:: In Wuhan, China, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported and caused coronavirus disease 19 (COVID-19). The infection of coronavirus is pathogenic and highly transmittable which spread quickly around the world by human to human contact. Through genomic analysis it has been revealed that primary reservoir of SARSCoV-2 are bats due to having severe acute respiratory syndrome-like (SARS-like) viruses phylogenetically. The viral infection rapidly transmitted by human to human contact but the intermediate source of their origin and transfer is not known. Till date, any clinically approved vaccine or antiviral drug is not prepared against COVID-19. However, researchers and scientist have been evaluated some broad-spectrum of antiviral drugs against COVID-19 through clinical trials and found satisfactory clinical recovery. This review summarise the comparative analysis of the emergence and pathogenicity of COVID-19, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). This review also focused to development of effective vaccines or antidrug and also focused on an approach to practice therapeutic combinations to fight with this viral outbreak.

scholarly journals Montelukast and Coronavirus Disease 2019: A Scoping Review

2021 ◽  
Author(s):  
Niusha Sharifinejad ◽  
Samin Sharafian ◽  
Sana Salekmoghadam ◽  
Marzieh Tavakol ◽  
Mostafa Qorbani
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Scoping Review ◽  
Therapeutic Approach ◽  
Systematic Approach ◽  
Web Of Science ◽  
Antiviral Drug ◽  
Prophylactic Agent ◽  
Prophylactic Drug ◽  
The World

Coronavirus disease 2019 (COVID-19) is an emerging worldwide issue, that has affected a large number of people around the world. So far, many studies have aimed to develop a therapeutic approach against COVID-19. Montelukast (MK) is a safe asthma controller drug, which is considered as a potential antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review has a systematic approach to investigate the reports on the use of MK as a part of treatment or a prophylactic agent in COVID-19. The search was conducted in PubMed, Web of Science, and Scopus databases and yielded 35 studies containing the influence of MK on SARS-CoV-2. Ultimately, MK appears to be worth being used as an adjuvant therapeutic and prophylactic drug against SARS-CoV-2. Nevertheless, more clinical trials are required to accurately investigate its effectiveness.

COVID-19: Are Experimental Drugs Cure or Ill?

2021 ◽  
Vol 16 ◽  
Author(s):  
Bensu Karahalil ◽  
Aylin Elkama
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Adverse Effects ◽  
Antiviral Treatment ◽  
Herd Immunity ◽  
Mortality Rates ◽  
Death Rates ◽  
Experimental Drugs ◽  
Combined Use ◽  
The World

Background: Coronavirus disease 2019 (COVID-19) is a new strain of coronavirus. It is characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has quickly influenced all over the world since it spreads easily. Common symptoms are fever, cough, difficulty in breathing and muscle aches. Despite the urgent need to find an effective antiviral treatment, already available agents are being used alone or in combination all over the world. At the beginning of the pandemic, death rates of infection caused by COVID-19 are high but "is COVID-19 responsible for all deaths?", or “are there any contributions of the frequently used drugs in this period to these deaths?” Surely herd immunity plays a major role and has the contribution in the decline in mortality rates. Meanwhile, it is kept in mind that due to safety concerns, changes have also been made to the dosage and combined use of frequently used drugs. Objective: In this review, answers to two questions above and the safety of treatments, toxicities of agents involving chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopiravir/ritonavir, sarilumab, tocilizumab, siltuximab, corticosteroids and bromhexine which are the most frequently used in both Turkey and all over the world will be summarized. Conclusion: Among these drugs favipiravir seems the most promising drug due to more tolerable adverse effects. More clinical trials with large sample sizes are needed to find the most effective and safe drug for COVID-19 treatment.

scholarly journals In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

2020 ◽  
Vol 71 (15) ◽  
pp. 732-739 ◽  
Author(s):  
Xueting Yao ◽  
Fei Ye ◽  
Miao Zhang ◽  
Cheng Cui ◽  
Baoying Huang ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Safety Profile ◽  
Late Phase ◽  
Vero Cells ◽  
Lung Fluid ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Autoimmune Conditions ◽  
Dosing Regimens

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug’s safety profile. Results Hydroxychloroquine (EC50 = 0.72 μM) was found to be more potent than chloroquine (EC50 = 5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Conclusions Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

scholarly journals Natural Bioactive Molecules as Potential Agents Against SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Chen ◽  
Zhihao Wang ◽  
Yawen Wang ◽  
Yiping Li
Keyword(s):  
Life Cycle ◽  
Antiviral Drug ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Biological Information ◽  
Economic Damage ◽  
Host Proteins ◽  
The Past ◽  
Invasion Mechanisms ◽  
The World

In the past two decades, pandemics of several fatal coronaviruses have posed enormous challenges for public health, including SARS-CoV (2003), MERS-CoV (2012), and SARS-CoV-2 (2019). Among these, SARS-CoV-2 continues to ravage the world today and has lead to millions of deaths and incalculable economic damage. Till now, there is no clinically proven antiviral drug available for SARS-CoV-2. However, the bioactive molecules of natural origin, especially medicinal plants, have been proven to be potential resources in the treatment of SARS-CoV-2, acting at different stages of the viral life cycle and targeting different viral or host proteins, such as PLpro, 3CLpro, RdRp, helicase, spike, ACE2, and TMPRSS2. They provide a viable strategy to develop therapeutic agents. This review presents fundamental biological information on SARS-CoV-2, including the viral biological characteristics and invasion mechanisms. It also summarizes the reported natural bioactive molecules with anti-coronavirus properties, arranged by their different targets in the life cycle of viral infection of human cells, and discusses the prospects of these bioactive molecules for the treatment of COVID-19.

scholarly journals Understanding the Molecular Mechanism(s) of SARS-CoV2 Infection and Propagation in Human to Discover Potential Preventive and Therapeutic Approach

2020 ◽  
Author(s):  
Dhruv Kumar
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Molecular Mechanism ◽  
Therapeutic Approach ◽  
Hubei Province ◽  
Human Cells ◽  
Huge Number ◽  
The World ◽  
Novel Coronavirus

In December 2019, outbreak of novel coronavirus (COVID-19) occurred in Wuhan, Hubei Province, China and exported across the world leading to thousands of deaths and millions of suspected cases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection into the host undergoes a huge number of complex replicative machineries which still remains unclear. Understanding the mechanism (s) of replication and mode of infection of SARS-CoV2 to human cells will help us in the development of novel vaccines or drugs for the eradication and prevention of the disease. This review compiles the knowledge of SARS-CoV2 replicative machinery, mode of infection to the human cells and the development of drugs and vaccines which are currently under clinical trials.

scholarly journals A comparative analysis of SARS-CoV-2 antivirals characterizes 3CLpro inhibitor PF-00835231 as a potential new treatment for COVID-19

2021 ◽  
Author(s):  
Maren de Vries ◽  
Adil S. Mohamed ◽  
Rachel A. Prescott ◽  
Ana M. Valero-Jimenez ◽  
Ludovic Desvignes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Life Cycle ◽  
Comparative Analysis ◽  
Airway Epithelium ◽  
Antiviral Drug ◽  
Viral Polymerase ◽  
Direct Acting Antiviral ◽  
Polymerase Inhibitor ◽  
Direct Acting

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CLpro (Mpro). The drug candidate PF-00835231 is the active compound of the first anti-3CLpro regimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the pre-clinical 3CLpro inhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A549+ACE2 cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A549+ACE2 cells and validates PF-00835231’s early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations. Finally, we show that the efflux transporter P-glycoprotein, which was previously suggested to diminish PF-00835231’s efficacy based on experiments in monkey kidney Vero E6 cells, does not negatively impact PF-00835231 efficacy in either A549+ACE2 cells or human polarized airway epithelial cultures. Thus, our study provides in vitro evidence for the potential of PF-00835231 as an effective SARS-CoV-2 antiviral and addresses concerns that emerged based on prior studies in non-human in vitro models. Importance: The arsenal of SARS-CoV-2 specific antiviral drugs is extremely limited. Only one direct-acting antiviral drug is currently approved, the viral polymerase inhibitor remdesivir, and it has limited efficacy. Thus, there is a substantial need to develop additional antiviral compounds with minimal side effects and alternate viral targets. One such alternate target is its main protease, 3CLpro (Mpro), an essential component of the SARS-CoV-2 life cycle processing the viral polyprotein into the components of the viral polymerase complex. In this study, we characterize a novel antiviral drug, PF-00835231, which is the active component of the first-in-class 3CLpro-targeting regimen in clinical trials. Using 3D in vitro models of the human airway epithelium, we demonstrate the antiviral potential of PF-00835231 for inhibition of SARS-CoV-2.

scholarly journals Repurposing Interleukin-6 Inhibitors to Combat COVID-19

2020 ◽  
Vol 3 (2) ◽  
pp. 52-55
Author(s):  
Shumei Kato ◽  
Razelle Kurzrock
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Severe Acute Respiratory Syndrome ◽  
Interleukin 6 ◽  
Causes Of Death ◽  
Distress Syndrome ◽  
Cytokine Storm ◽  
Novel Treatment ◽  
The Us ◽  
The World ◽  
Potential Use

ABSTRACT Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a pandemic with major implications across the world. One of the most frequent causes of death from SARS-CoV-2 is fatal pneumonia from coronavirus disease 2019 (COVID-19), which is associated with the development of acute respiratory distress syndrome (ARDS). To date (as of April 2, 2020), other than supportive measures, there are no efficient therapeutic options for COVID-19–related ARDS, although the US Food and Drug Administration recently granted emergency authorization for the use of hydroxychoroquine/chloroquine for this indication (which is usually given with azithromycin). Although the pathogenesis for ARDS is under investigation, one of the major culprits is considered to be cytokine storm, especially from interleukin 6 (IL-6) release. Herein, we review potential use of IL-6 inhibitors, several of which are approved for other disease conditions, as potential novel treatment for the management of COVID-19–related ARDS.

scholarly journals Medicines for the Treatment Of COVID-19: Awaiting the Evidence

2020 ◽  
Vol 33 (7-8) ◽  
pp. 500
Author(s):  
Natalia Marto ◽  
Emília C. Monteiro
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
The Novel ◽  
Off Label Use ◽  
Promising Candidate ◽  
Off Label ◽  
Health Authorities ◽  
Investigational Drugs ◽  
The World ◽  
Repurposed Drugs

The novel severe acute respiratory syndrome coronavirus 2 is the cause of Coronavirus Disease 2019, a new illness with no effective treatment or vaccine that has reached pandemic proportions. In this document, we analyze how health authorities and agencies around the world position themselves regarding the off-label use of repurposed drugs or new investigational drugs to treat Coronavirus Disease 2019. We review the most promising candidate medicines, including available evidence, clinical recommendations and current options for access. Our concluding remarks stress the importance of administering off-label and investigational drugs in the setting of clinical trials, or at least in standardized scenarios, to generate as much scientific knowledge as achievable while engaging in the best efforts to treat patients and save lives.

Remdesivir, A Potential Drug for COVID-19 Treatment: A New Hope

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Kuldeep Singh ◽  
Dilpreet Singh ◽  
Karan Razdan
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Recovery Rate ◽  
Potential Drug ◽  
Regulatory Status ◽  
The World ◽  
Polymerase Inhibitor

Objective: Coronavirus Diease-2019 (COVID-19) is a pandemic outbreak in the world and is the leading cause of Severe Acute Respiratory Syndrome (SARS). Methods: Currently, many drugs/therapies have been tested for COVID-19 which responded sub optimally to the patients. Remdesivir is a RNA polymerase inhibitor found promising results in ongoing clinical trials and shows faster recovery rate in COVID-19 patients. Currently, USFDA approves for emergent use of this drug in severe COVID-19 patients. Results: In this review, we discussed brief overview of biopharmaceutical and pharmacological aspects of Remdesivir. Moreover, ongoing regulatory status of Remdesivir by official bodies has also been described.

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