scholarly journals A Review of SARS-CoV-2 and the Ongoing Clinical Trials

2020 ◽  
Vol 21 (7) ◽  
pp. 2657 ◽  
Author(s):  
Yung-Fang Tu ◽  
Chian-Shiu Chien ◽  
Aliaksandr A. Yarmishyn ◽  
Yi-Ying Lin ◽  
Yung-Hung Luo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Global Economy ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Molecular Characteristics ◽  
Human Society ◽  
Virus Infections ◽  
Novel Coronavirus

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.

scholarly journals An evidence-based systematic review on emerging therapeutic and preventive strategies to treat novel coronavirus (SARS-CoV-2) during an outbreak scenario

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anupama M. Gudadappanavar ◽  
Jyoti Benni
Keyword(s):  
Antiviral Drug ◽  
Drug Repurposing ◽  
Respiratory Illness ◽  
World Health ◽  
Recombinant Vaccines ◽  
Subunit Vaccines ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Full Length Genome

AbstractA novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.

scholarly journals Safety and Effectiveness of Favipiravir for Novel Coronavirus (COVID-19): A Rapid Review of Available Evidence

2021 ◽  
Author(s):  
Mohammadreza Mobinizadeh ◽  
Morteza Arab-Zozani
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Therapeutic Potential ◽  
Data Extraction ◽  
Rapid Review ◽  
Eligibility Criteria ◽  
Clinical Trial Registration ◽  
Registration System ◽  
Novel Coronavirus ◽  
First Time

Context: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared for the first time in December 2019 in Wuhan, China. Due to the lack of unified and integrated evidence for Favipiravir, this study was conducted to rapidly review the existing evidence to help evidence-based decision-making on the therapeutic potential of this drug in the treatment of COVID-19 patients. Evidence Acquisition: This study is a rapid Health Technology Assessment (HTA). By searching pertinent databases, the research team collected relevant articles and tried to create a policy guide through a thematic approach. This rapid review was done in four steps: (1) Searching for evidence through databases; (2) screening the evidence considering eligibility criteria; (3) data extraction; and (4) analyzing the data through thematic analysis. Results: After applying the inclusion criteria, four studies were finally found, including three review studies and a clinical trial that was temporarily removed by its publisher from the journal’s website. After searching the sources mentioned in the articles, two ongoing clinical trials were found in China. Also, by searching the clinical trial website, www.clinicaltrials.gov, five clinical trials were found in the search. The result of the search in the clinical trial registration system in Iran showed a study that is in the process of patient recruitment. A limited number of other articles were found, mostly in the form of reflections from physicians or researchers and letters to editors who have predicted the drug’s performance on SARS-CoV-2, which needs further clinical study to be approved. Conclusions: With the available evidence, it is not possible to make a definite conclusion about the safety and efficacy of Favipiravir in the treatment of patients with COVID-19.

scholarly journals The Anatomy of the SARS-CoV-2 Biomedical Literature: Introducing the CovidX Network Algorithm for Drug Repurposing Recommendation

10.2196/21169 ◽  
2020 ◽  
Vol 22 (8) ◽  
pp. e21169
Author(s):  
Lyndsey Elaine Gates ◽  
Ahmed Abdeen Hamed
Keyword(s):  
Clinical Trials ◽  
Language Processing ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Biomedical Literature ◽  
Drug Candidates ◽  
Fast Development ◽  
Drug Knowledge ◽  
Biomedical Publications ◽  
Multiple Drugs

Background Driven by the COVID-19 pandemic and the dire need to discover an antiviral drug, we explored the landscape of the SARS-CoV-2 biomedical publications to identify potential treatments. Objective The aims of this study are to identify off-label drugs that may have benefits for the coronavirus disease pandemic, present a novel ranking algorithm called CovidX to recommend existing drugs for potential repurposing, and validate the literature-based outcome with drug knowledge available in clinical trials. Methods To achieve such objectives, we applied natural language processing techniques to identify drugs and linked entities (eg, disease, gene, protein, chemical compounds). When such entities are linked, they form a map that can be further explored using network science tools. The CovidX algorithm was based upon a notion that we called “diversity.” A diversity score for a given drug was calculated by measuring how “diverse” a drug is calculated using various biological entities (regardless of the cardinality of actual instances in each category). The algorithm validates the ranking and awards those drugs that are currently being investigated in open clinical trials. The rationale behind the open clinical trial is to provide a validating mechanism of the PubMed results. This ensures providing up to date evidence of the fast development of this disease. Results From the analyzed biomedical literature, the algorithm identified 30 possible drug candidates for repurposing, ranked them accordingly, and validated the ranking outcomes against evidence from clinical trials. The top 10 candidates according to our algorithm are hydroxychloroquine, azithromycin, chloroquine, ritonavir, losartan, remdesivir, favipiravir, methylprednisolone, rapamycin, and tilorone dihydrochloride. Conclusions The ranking shows both consistency and promise in identifying drugs that can be repurposed. We believe, however, the full treatment to be a multifaceted, adjuvant approach where multiple drugs may need to be taken at the same time.

scholarly journals Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation

2021 ◽  
Vol 22 (17) ◽  
pp. 9427
Author(s):  
Simone Di Micco ◽  
Simona Musella ◽  
Marina Sala ◽  
Maria C. Scala ◽  
Graciela Andrei ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Fast Response ◽  
Main Protease ◽  
Promising Target ◽  
Peptide Derivatives ◽  
Novel Coronavirus ◽  
Derivatives Of

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (Mpro), is essential for viral replication, making it a most promising target for antiviral drug development. Recently, we adopted the drug repurposing as appropriate strategy to give fast response to global COVID-19 epidemic, by demonstrating that the zonulin octapeptide inhibitor AT1001 (Larazotide acetate) binds Mpro catalytic domain. Thus, in the present study we tried to investigate the antiviral activity of AT1001, along with five derivatives, by cell-based assays. Our results provide with the identification of AT1001 peptide molecular framework for lead optimization step to develop new generations of antiviral agents of SARS-CoV-2 with an improved biological activity, expanding the chance for success in clinical trials.

scholarly journals Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Miguel Angel Martinez
Keyword(s):  
Ebola Virus ◽  
Therapeutic Potential ◽  
High Morbidity ◽  
Virus Infections ◽  
Humanized Mouse Model ◽  
Proinflammatory Responses ◽  
Inflammatory State ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Respiratory Coronavirus

ABSTRACT Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

scholarly journals PHYTOCHEMICALS IN THE TREATMENT OF ARTHRITIS: CURRENT KNOWLEDGE

2020 ◽  
pp. 1-6
Author(s):  
SOURAV BHATTACHARYA ◽  
SUDIP KUMAR MANDAL ◽  
MD. SEMIMUL AKHTAR ◽  
DIPRA DASTIDER ◽  
SIPRA SARKAR ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chlorogenic Acid ◽  
Proinflammatory Cytokines ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Joint Inflammation ◽  
Present Review

The objective of the present review is to evaluate the therapeutic potential of phytochemicals against arthritis, which is asymptomatic disorder of chronic joint inflammation followed by swelling and pain. Here, we discussed about the anti-arthritic activity of many phytomolecules such as Norisoboldine, Berberine, Triptolide, Hesperidin Hesperidin, Madecassocide, Hydroxy napthoquinone, Ginsenoside, Cryptotanshinone, Kirenol, Thymoquinone, Chlorogenic acid, Curcumin, Bromelain, Andrographolide and Allicin. These compounds are able to control inflammatory responses, proinflammatory cytokines, osteoclast differentiation and to prevent bone erosion in the joints. In this article, we reviewed anti-arthritic activities of phytichemicals from 2011-2019, using various scientific websites like PubMed, Google Scholar, Science Direct etc. Till date clinical trials conducted with anti-arthritic phytomolecules are very less. Hence, more clinical trials are needed to bring plant molecules as safe and effective anti-arthritic drugs in the market, either alone or in combination with other anti-arthritic agents.

scholarly journals In silico Drug Repurposing for COVID-19: Targeting SARS-CoV-2 Proteins through Docking and Quantum Mechanical Scoring

2020 ◽  
Author(s):  
Claudio Cavasotto ◽  
Juan Di Filippo
Keyword(s):  
Clinical Trials ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
World Health ◽  
Quantum Mechanical ◽  
S Protein ◽  
Compound Screening ◽  
Health Organization ◽  
Approved Drugs

In December 2019, an infectious disease caused by the coronavirus SARS-CoV-2 appeared in Wuhan, China. This disease (COVID-19) spread rapidly worldwide, and on March 2020 was declared a pandemic by the World Health Organization (WHO). Today, almost 1,5 million people have been infected, with more than 85,000 casualties. Today, no vaccine nor antiviral drug is available. While the development of a vaccine might take at least a year, and for a novel drug, even longer; finding a new use to an old drug (drug repurposing) could be the most effective strategy. We present a docking-based screening using a quantum mechanical scoring of a library built from approved drugs and compounds undergoing clinical trials, against three SARS-CoV-2 target proteins: the spike or S-protein, and two proteases, the main protease and the papain-like<br>protease. The S-protein binds directly to the Angiotensin Converting Enzyme 2 receptor of the human host cell surface, while the two proteases process viral polyproteins.<br>Following the anaylysis of our structure-based compound screening, we propose several structurally diverse compounds (either FDA-approved or in clinical trials) that could display antiviral activity against SARS-CoV-2. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the disease. We hope that these findings may contribute to the rational drug design against COVID-19.

scholarly journals In silico Drug Repurposing for COVID-19: Targeting SARS-CoV-2 Proteins through Docking and Quantum Mechanical Scoring

2020 ◽  
Author(s):  
Claudio Cavasotto ◽  
Juan Di Filippo
Keyword(s):  
Clinical Trials ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
World Health ◽  
Quantum Mechanical ◽  
Chemical Library ◽  
S Protein ◽  
Health Organization ◽  
Approved Drugs

In December 2019, an infectious disease caused by the coronavirus SARS-CoV-2 appeared in Wuhan, China. This disease (COVID-19) spread rapidly worldwide, and on March 2020 was declared a pandemic by the World Health Organization (WHO). Today, more than 4.7 million people have been infected, with almost 320,000 casualties, while no vaccine nor antiviral drug is in sight. The development of a vaccine might take at least a year, and even longer for a novel drug; thus, finding a new use to an old drug (drug repurposing) could be the most effective strategy. We present a high-throughput docking approach using a novel quantum mechanical scoring for screening a chemical library of ~11,500 molecules built from FDA-approved drugs and compounds undergoing clinical trials, against three SARS-CoV-2 target proteins: the spike or S-protein, and two proteases, the main protease and the papain-like protease. The S-protein binds directly to the Angiotensin Converting Enzyme 2 receptor of the human host cell surface, while the two proteases process viral polyproteins. Following the analysis of our structure-based virtual screening, we propose several structurally diverse compounds that could display antiviral activity against SARS-CoV-2. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the disease. We hope that these findings may contribute to the rational drug design against COVID-19.

Repositioning of drugs to counter COVID-19 pandemic - An Insight

2020 ◽  
Vol 21 ◽  
Author(s):  
Sai M. Akilesh ◽  
Rajesh J ◽  
Dhanabal Palanisamy ◽  
Ashish Wadhwani
Keyword(s):  
Clinical Trials ◽  
Drug Repurposing ◽  
Review Article ◽  
The Novel ◽  
Phylogenetic Relation ◽  
Scientific Investigations ◽  
Realistic Approach ◽  
Life Threatening ◽  
Novel Coronavirus ◽  
Approved Drugs

: COVID-19 is a coronavirus pandemic, caused by the novel coronavirus 2 (SARS-CoV-2) severe acute respiratory syndrome. The devastating impact of this novel coronavirus outbreak has necessitated the need for rapid and effective anti-viral therapies against SARS-CoV-2, to contain the spread of disease and importantly, alleviate the severe life-threatening symptoms and disorders. Drug repurposing strategy offers an attractive, immediate and realistic approach to tackle this growing pandemic of COVID-19. Due to the similarities with SARS-CoV-1 virus and phylogenetic relation to MERS-CoV virus, accelerated screening of approved drugs and development of repositioning strategies have proved to be critical in the survival of many COVID-19 patients. Numerous scientific investigations from the initial years of coronavirus outbreak along with upcoming advances of immunotherapy and vaccines may prove to be beneficial. Currently, several repurposing strategies are under different phases of clinical trials and provide with definitive framework for the development of future therapies for the effective treatment of COVID-19. This review article summarizes the latest developments and trends in drug repurposing strategy for COVID-19 treatment.

Milk Oligosaccharides and Lectins as Candidates for Clinical Trials Against Covid-19

2020 ◽  
Vol 16 ◽  
Author(s):  
Mourad Errasfa
Keyword(s):  
Clinical Trials ◽  
Molecular Species ◽  
Global Economy ◽  
Therapeutic Potential ◽  
Scientific Evidence ◽  
Research Work ◽  
Camel Milk ◽  
Milk Oligosaccharides ◽  
Binding Properties ◽  
Scientific Publications

Background: Covid-19 pandemia is causing a very high death toll around the world and a serious fall in the global economy. Many clinical trials are currently underway to check the effectiveness of some known drugs. The physiopathology associated with the virus infection is currently better understood and good prophylactic drug therapies are implemented, such as antibiotics and blood thinners, though, no specific drugs against SARS-Cov-2 were developed yet. Objective: In the present research work, it is aimed to carry out a bibliographic investigation on some active molecular species that could be used against Covid-19, based on their chemical properties to bind to glycoproteins. In the case of SARS-Cov-2, the targeted glycoprotein is the surface virus spike S glycoprotein, that the virus uses to attach to and invade human cells. It is of high pharmacological value to investigate possible active natural substances endowed with a property to bind glycoproteins. In this line of research, oligosaccharides and lectins are two molecular species that have glycoprotein binding properties. Methods: A bibliographic research was carried out on oligosaccharides and lectins in various sources of scientific publications. Relevant chemical and pharmacological properties of oligosaccharides and lectins were searched and their main natural sources were identified. Results: In the present paper, I summarize some scientific evidence to support the therapeutic potential of camel milk as a source of oligosaccharides and its possible use as a functional diet in parallel to drug therapies of Covid-19. On the other hand, sugar- and glycoprotein binding properties of some lectins of plant and seaweed origin are reported, and their pharmaceutical use is underlined. Conclusion: In the present study, scientific evidence was documented that encouraged further clinical investigations on camel milk oligosaccharides and lectins of plant and seaweed origin in the management of Covid-19 physiopathology.

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