COVID-19 Global Pandemic Fight by Drugs: A Mini-Review on Hope and Hype

: Coronavirus disease 2019 (Covid-19) is caused by the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) was firstly identified in the city of Wuhan of China in December 2019, which was spread and become a global issue due to its high transmission rate. To date, the outbreak of COVID-19 has resulted in infection to 150,356,672 people and the death of 3,167,010 patients. It paralyzed the economy of all the countries worldwide. Unfortunately, no specific FDA-approved antiviral treatment or vaccine is available to curb the outbreak. Considering the possible mutations of SARS-CoV-2, the current medical emergency required a longer time for drug design and vaccine development. Drug repurposing is a promising option for potent therapeutic against the pandemic. The present review encompasses various drugs or appropriate combinations of already FDA-approved antimalarial, antiviral, anticancer, anti-inflammatory, and antibiotic therapeutic candidates for use in the clinical trials as a ray of hope against COVID-19. It is expected to deliver better clinical and laboratory outcomes of drugs as a prevention strategy for the eradication of the disease.

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Coronavirus Disease 2019 (COVID-19): Origin, Impact, and Drug Development

10.5772/intechopen.98358 ◽

2021 ◽

Author(s):

Amaresh Mishra ◽

Nisha Nair ◽

Amit K. Yadav ◽

Pratima Solanki ◽

Jaseela Majeed ◽

...

Keyword(s):

Vaccine Development ◽

Therapeutic Option ◽

Treatment Strategies ◽

Drug Repurposing ◽

Cost Effective ◽

High Sequence Identity ◽

Drug Candidates ◽

Global Pandemic ◽

The People ◽

Health Organization

At the end of December 2019, in Wuhan, China, a rapidly spreading unknown virus was reported to have caused coronavirus disease of 2019 (COVID-19). Origin linked to Wuhan’s wholesale food market where live animals are sold. This disease is caused by SARS Coronavirus-2 (SARS-CoV-2), which is closely related to the Severe Acute Respiratory Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This virus shares a high sequence identity with bat-derived SARS-like Coronavirus, which indicating its zoonotic origin. The virus spread globally, provoking widespread attention and panic. This Coronavirus is highly pathogenic and causes mild to severe respiratory disorders. Later, it was declared a global pandemic by the World Health Organization (WHO) due to its highly infectious nature and worldwide mortality rate. This virus is a single-stranded, positive-sense RNA genome, and its genome length about 26 to 32 kb that infects a broad range of vertebrates. The researchers worldwide focus on establishing treatment strategies on drug and vaccine development to prevent this COVID-19 pandemic. A drug repurposing approach has been used to identify a rapid treatment for the people affected by COVID-19, which could be cost-effective and bypass some Food and Drug Association (FDA) regulations to move quickly in phase-3 trials. However, there is no promising therapeutic option available yet. This book chapter addresses current information about the COVID-19 disease, including its origins, impacts, and the novel potential drug candidates that can help treat the COVID-19.

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The Drug Repurposing for COVID-19 Clinical Trials Provide Very Effective Therapeutic Combinations: Lessons Learned From Major Clinical Studies

Frontiers in Pharmacology ◽

10.3389/fphar.2021.704205 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chiranjib Chakraborty ◽

Ashish Ranjan Sharma ◽

Manojit Bhattacharya ◽

Govindasamy Agoramoorthy ◽

Sang-Soo Lee

Keyword(s):

Clinical Trials ◽

Single Molecule ◽

Vaccine Development ◽

Drug Repurposing ◽

Lessons Learned ◽

Successful Outcome ◽

Plasma Therapy ◽

Therapeutic Outcomes ◽

Therapeutic Molecules ◽

In The Beginning

SARS-CoV-2 has spread across the globe in no time. In the beginning, people suffered due to the absence of efficacious drugs required to treat severely ill patients. Nevertheless, still, there are no established therapeutic molecules against the SARS-CoV-2. Therefore, repurposing of the drugs started against SARS-CoV-2, due to which several drugs were approved for the treatment of COVID-19 patients. This paper reviewed the treatment regime for COVID-19 through drug repurposing from December 8, 2019 (the day when WHO recognized COVID-19 as a pandemic) until today. We have reviewed all the clinical trials from RECOVERY trials, ACTT-1 and ACTT-2 study group, and other major clinical trial platforms published in highly reputed journals such as NEJM, Lancet, etc. In addition to single-molecule therapy, several combination therapies were also evaluated to understand the treatment of COVID-19 from these significant clinical trials. To date, several lessons have been learned on the therapeutic outcomes for COVID-19. The paper also outlines the experiences gained during the repurposing of therapeutic molecules (hydroxychloroquine, ritonavir/ lopinavir, favipiravir, remdesivir, ivermectin, dexamethasone, camostatmesylate, and heparin), immunotherapeutic molecules (tocilizumab, mavrilimumab, baricitinib, and interferons), combination therapy, and convalescent plasma therapy to treat COVID-19 patients. We summarized that anti-viral therapeutic (remdesivir) and immunotherapeutic (tocilizumab, dexamethasone, and baricitinib) therapy showed some beneficial outcomes. Until March 2021, 4952 clinical trials have been registered in ClinicalTrials.gov toward the drug and vaccine development for COVID-19. More than 100 countries have participated in contributing to these clinical trials. Other than the registered clinical trials (medium to large-size), several small-size clinical trials have also been conducted from time to time to evaluate the treatment of COVID-19. Four molecules showed beneficial therapeutic to treat COVID-19 patients. The short-term repurposing of the existing drug may provide a successful outcome for COVID-19 patients. Therefore, more clinical trials can be initiated using potential anti-viral molecules by evaluating in different phases of clinical trials.

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Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines

Vaccines ◽

10.3390/vaccines9090992 ◽

2021 ◽

Vol 9 (9) ◽

pp. 992

Author(s):

Puna Maya Maharjan ◽

Sunghwa Choe

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Vaccine Development ◽

Production Systems ◽

Transmission Rate ◽

Neutralizing Antibody ◽

Current Status ◽

Economic Losses ◽

Phase 2 Clinical Trial ◽

Clinical Trial Results

The prevalence of the coronavirus disease 2019 (COVID-19) pandemic in its second year has led to massive global human and economic losses. The high transmission rate and the emergence of diverse SARS-CoV-2 variants demand rapid and effective approaches to preventing the spread, diagnosing on time, and treating affected people. Several COVID-19 vaccines are being developed using different production systems, including plants, which promises the production of cheap, safe, stable, and effective vaccines. The potential of a plant-based system for rapid production at a commercial scale and for a quick response to an infectious disease outbreak has been demonstrated by the marketing of carrot-cell-produced taliglucerase alfa (Elelyso) for Gaucher disease and tobacco-produced monoclonal antibodies (ZMapp) for the 2014 Ebola outbreak. Currently, two plant-based COVID-19 vaccine candidates, coronavirus virus-like particle (CoVLP) and Kentucky Bioprocessing (KBP)-201, are in clinical trials, and many more are in the preclinical stage. Interim phase 2 clinical trial results have revealed the high safety and efficacy of the CoVLP vaccine, with 10 times more neutralizing antibody responses compared to those present in a convalescent patient’s plasma. The clinical trial of the CoVLP vaccine could be concluded by the end of 2021, and the vaccine could be available for public immunization thereafter. This review encapsulates the efforts made in plant-based COVID-19 vaccine development, the strategies and technologies implemented, and the progress accomplished in clinical trials and preclinical studies so far.

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A review on the SARS-CoV-2 mediated global pandemic: proximal origin, pathogenicity and therapeutic approaches

10.31219/osf.io/fpqsw ◽

2020 ◽

Author(s):

Soumi Chatterjee ◽

Bikram Dhara ◽

Dattatreya Mukherjee ◽

Arup Kumar Mitra

Keyword(s):

Vaccine Development ◽

Geographical Area ◽

Antiviral Drug ◽

Drug Repurposing ◽

The Novel ◽

Therapeutic Approaches ◽

Health Crisis ◽

Public Health Crisis ◽

Global Pandemic ◽

Viral Outbreak

The world is amidst a public health crisis as the pandemic has shook us to the core. The COVID-19 caused by the novel SARS-CoV-2 is of zoonotic origin and this tries to explain what could have been the possible proximal origins for the disease in humans. Our review aims at addressing the question like what structural or genomic vicissitude enabled the viral outbreak across genera and so efficiently infect the human populace across the globe. We also try to discuss the prospect of drug repurposing and scope for vaccine development considering the rapid genome modification of the virus. Another finding lies into the action of pre-existing drugs when they are applied in combination and probably that shades some light on the therapeutic approaches. Several investigation have been performed but we are still in search of a novel antiviral drug. With that vision, our focus shifted on the evaluation of existing drugs with positive response against the novel corona virus. We also try discussing certain trends including increased immunity to the disease in the population from a particular geographical area.

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Systematic Search for SARS-CoV-2 Main Protease Inhibitors for Drug Repurposing: Ethacrynic Acid as a Potential Drug

Viruses ◽

10.3390/v13010106 ◽

2021 ◽

Vol 13 (1) ◽

pp. 106

Author(s):

Camilla Isgrò ◽

Anna Maria Sardanelli ◽

Luigi Leonardo Palese

Keyword(s):

Therapeutic Strategy ◽

Ethacrynic Acid ◽

Vaccine Development ◽

Antiviral Drug ◽

Drug Repurposing ◽

High Morbidity ◽

Global Pandemic ◽

Main Protease ◽

Starting Point ◽

Effective Therapeutic Strategy

In 2019 an outbreak occurred which resulted in a global pandemic. The causative agent has been identified in a virus belonging to the Coronaviridae family, similar to the agent of SARS, referred to as SARS-CoV-2. This epidemic spread rapidly globally with high morbidity and mortality. Although vaccine development is at a very advanced stage, there are currently no truly effective antiviral drugs to treat SARS-CoV-2 infection. In this study we present systematic and integrative antiviral drug repurposing effort aimed at identifying, among the drugs already authorized for clinical use, some active inhibitors of the SARS-CoV-2 main protease. The most important result of this analysis is the demonstration that ethacrynic acid, a powerful diuretic, is revealed to be an effective inhibitor of SARS-CoV-2 main protease. Even with all the necessary cautions, given the particular nature of this drug, these data can be the starting point for the development of an effective therapeutic strategy against SARS-CoV-2.

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Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS-S and MERS-S pseudotyped particles

10.1101/2020.07.10.197988 ◽

2020 ◽

Cited By ~ 3

Author(s):

Catherine Z. Chen ◽

Miao Xu ◽

Manisha Pradhan ◽

Kirill Gorshkov ◽

Jennifer Petersen ◽

...

Keyword(s):

High Throughput ◽

Broad Spectrum ◽

Vaccine Development ◽

Drug Repurposing ◽

Cell Entry ◽

Entry Inhibitors ◽

Small Molecule Drugs ◽

Global Pandemic ◽

Initial Stage ◽

Approved Drugs

AbstractWhile vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry. This work should contribute to the development of effective treatments against the initial stage of viral infection, thus reducing viral burden in COVID-19 patients.Abstract Figure

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Elucidating the drug repurposing spectra of COVID-19 with its analogues SARS and MERS

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210225114733 ◽

2021 ◽

Vol 21 ◽

Author(s):

Jayanti Mishra ◽

Chakrawarti Prasun ◽

P.K. Sahoo ◽

Maya S Nair

Keyword(s):

Clinical Trials ◽

Vaccine Development ◽

Virus Disease ◽

Cathepsin L ◽

Drug Repurposing ◽

Disease Treatment ◽

Acceptable Alternative ◽

Drug Molecules ◽

The World ◽

Novel Drug

: COVID-19 disease, caused by the SARS CoV-2 virus, has been announced as Pandemic by the WHO. To date it has affected almost every part of the world, more than 39.8 million people were infected and up to 1.11 million have lost their lives. Currently, there has been no success to develop measures to cure the disease. Additionally, the vaccine development may take several months, and many novel drug molecules attempted have been fallen short of achieving success yet. Hence, an effective alternative solution is a need for these darkest hours. Repurposing of drugs has already proved efficacy in diseases, like, and it significantly provides the most acceptable alternative. There are hundreds of drug molecules approved for clinical trials by the FDA. SARS COV 2 virus has shown resemblance with enzyme targets such as 3CLpro/Mpro, RdRp, Cathepsin L, and TMPRSS2 with SARS CoV and MERS CoV that gives an option to use drugs that have shown efficacy in these viruses for COVID-19 (Corona Virus Disease) treatment. This review focuses on why repurposing could provide a better alternative in COVID-19 treatment and the similarity in the structural and progression of infection of these viruses gives a direction and validation to evaluate the drugs approved for SARS and MERS against COVID-19. It has been indicated that multiple therapeutic options that demonstrate efficacy against SARS CoV 2 are available to mitigate the potential emergence of COVID-19 infection.

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COVID-19: Socio-Economic Implications for Pakistan

Global Economics Review ◽

10.31703/ger.2020(v-iii).12 ◽

2020 ◽

Vol V (III) ◽

pp. 131-142

Author(s):

Ijaz Khalid ◽

Aneela Akbar ◽

Hina Malik

Keyword(s):

Developing Countries ◽

Limited Resources ◽

Economic Implications ◽

The Public ◽

Chinese City ◽

Global Pandemic ◽

The People ◽

Global Issue ◽

The World ◽

The City

The paper analyzes the global pandemic of COVID-19, its evolution, development and its implications on the world and specifically Pakistan. Sparkly, it emerged in the Chinese city of Wuhan, was restricted to the city for less than a month, but currently, the virus has engrossed the whole world. This part of the study investigates both developed and developing countries responses to deal with the dominant global issue. The study focused on Pakistan's response to COVID-19 being damaged by War on Terror and political instability. The paper concluded that Pakistan very smartly responded to the pandemic by applying smart lockdown within its limited resources to contain the virus and maintained a balance between saving lives and saving livelihoods. This piece of paper also finds that, like in other developing countries, the pandemic also has severe Socio-economic implications as the economically of the business went down, investment came to its lowest level that heavily marked Pakistan economically unsound. Socially speaking, the virus created fear and totally break down the public gathering that made the people psychologically unhealthy.

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

Therapeutic Advances in Infectious Disease ◽

10.1177/20499361211063016 ◽

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.

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Covid19db – An online database of trials of medicinal products to prevent or treat COVID-19, with a specific focus on drug repurposing

10.1101/2020.05.27.20114371 ◽

2020 ◽

Cited By ~ 2

Author(s):

Pan Pantziarka ◽

Liese Vandeborne ◽

Lydie Meheus ◽

Gauthier Bouche

Keyword(s):

Clinical Trials ◽

Open Access ◽

Drug Repurposing ◽

Online Database ◽

Medicinal Products ◽

Global Pandemic ◽

Repurposed Drugs ◽

Single Data ◽

Clinical Trials Registry ◽

User Friendly

AbstractBackgroundThe global pandemic caused by SARS-CoV-2 virus has prompted an unprecedented international effort to seek medicines for prevention and treatment of infection. Drug repurposing has played a key part in this response. The rapid increase in trial activity has raised questions about efficiency and lack of coordination. Our objective was to develop a user-friendly, open access, online database of interventional trials of medicinal products to monitor and rapidly identify trials of medicinal products.Methods and FindingsUsing the US clinicaltrials.gov (NCT) registry, the EU Clinical Trials Register (EUCTR) and the WHO International Clinical Trials Registry Platform (WHO ICTRP), we identified all COVID-19 trials of medicinal products and combined data from the 3 sources into a single data table. Trials that were out of scope and duplicates were excluded. A manual encoding was performed to ascertain key information (e.g. trial aim, type of intervention etc). The database, Covid19db, was published online at: http://www.redo-project.org/covid19db/. Descriptive statistics of the database from April 4th 2020 through to May 19th show an increase from 186 to 955 trials, or an average of 17 new trials registered per day. Over this period, the proportion of trials including a repurposing arm decreased slightly over time (from a maximum of 75% to 68% at the end of the covered period) as did the proportion of trials aiming to prevent infection (from a maximum of 16% to 12% at the end of the covered period). The most popular intervention is hydroxychloroquine (180 trials), followed by azithromycin (57 trials), chloroquine, tocilizumab and lopinavir/ritonavir (36 trials). Total planned enrolment is 468,559 participants as of 19th May 2020.Conclusionswe have developed an open access, online and regularly updated tool to monitor clinical trials of medicinal products to prevent or treat infection by SARS-CoV-2 globally. Our analysis shows a high number of ‘me-too’ trials, in particular for some repurposed drugs, such as hydroxychloroquine, azithromycin and tocilizumab, substantiating calls for better coordination and better use of trial resources.

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