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

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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Remdesivir: Critical Clinical Appraisal for COVID 19 Treatment

Drug Research ◽

10.1055/a-1288-4078 ◽

2020 ◽

Author(s):

Saptarshi Chatterjee

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Clinical Studies ◽

Promising Result ◽

Drug Repurposing ◽

In Vitro Studies ◽

Therapeutic Molecules ◽

Regulatory Aspect ◽

Plausible Mechanism

AbstractRemdesivir is presently been considered as ‘molecule of hope’ to curb the menace of COVID19. Non-availability of any USFDA approved drug has led to several attempt of drug-repurposing and development of new therapeutic molecules. However, Remdesivir has been found to be effective against a broad range of virus including SARS, MERS and COVID 19 through in-vitro studies. Several clinical research attempt are presently being conducted showing promising result yet not conclusive. This review summarized all such clinical trials to critically appraise the usage of Remdesivir against COVID 19 along with the publications related to the results of the clinical studies. The present regulatory aspect i. e. Emergency Use Authorization (EYA) and information of molecule and plausible mechanism is also dealt.

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An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?

Frontiers in Pharmacology ◽

10.3389/fphar.2021.632677 ◽

2021 ◽

Vol 12 ◽

Cited By ~ 1

Author(s):

Omkar Indari ◽

Shweta Jakhmola ◽

Elangovan Manivannan ◽

Hem Chandra Jha

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Drug Repurposing ◽

Clinical Findings ◽

Open Label ◽

Plasma Therapy ◽

Clinical Safety ◽

Treatment Research ◽

Repurposed Drugs ◽

Approved Drugs

COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.

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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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Services Marketing of COVID-19 Vaccines in the Present Scenario

International Journal for Modern Trends in Science and Technology - RTT2020 ◽

10.46501/ijmtst061127 ◽

2020 ◽

Vol 6 (11) ◽

pp. 143-146

Author(s):

Dr. Rachana Nagar Dr. Naveen Sharma and Garima Sharma

Keyword(s):

Clinical Trials ◽

Infectious Diseases ◽

Vaccine Development ◽

Forecast Period ◽

Phase 3 ◽

Plasma Therapy ◽

Vaccine Candidates ◽

Market Growth ◽

University Of Oxford ◽

Prevention Trials

The global COVID-19 vaccines market is projected to reach USD 1,401 million by 2025 from USD 2,273 million in 2022, at a CAGR of -14.9% during the forecast period. The growth of the COVID vaccines market is attributed majorly to the rising number of people infected with COVID-19 and increasing funding for vaccine development. On the other hand, the global COVID-19 drugs market is projected to reach USD 2 million by 2025 from USD 165 million in 2020, at a CAGR of -57.8% during the forecast period. The growth of the COVID drugs market is primarily attributed to use of repurposed drugs for compassionate use, and the emergence of alternative therapies such as convalescent plasma therapy which were earlier used for treating epidemic diseases such as SARS, MERS, and H1N1. Moreover, collaborations between global organizations and governments of various nations to promote the supply of essential drugs and medical supplies are fueling the market growth. Researchers worldwide are working around the clock to find a vaccine against SARS-CoV-2, the virus causing the COVID-19 pandemic. The Herculean effort means that a fast-tracked vaccine could come to market anywhere from the end of 2020 to the middle of 2021. To date, just two coronavirus vaccine has been approved. Sputnik V – formerly known as Gam-COVID-Vac and developed by the Gamaleya Research Institute in Moscow – was approved by the Ministry of Health of the Russian Federation on 11 August. Experts have raised considerable concern about the vaccine’s safety and efficacy given it has not yet entered Phase 3 clinical trials. A second vaccine in Russia, EpiVacCorona, has also been granted regulatory approval, also without entering Phase 3 clinical trials. Operation Warp Speed (OWS) is a collaboration of several US federal government departments including Health and Human Services and its subagencies, Agriculture, Energy and Veterans Affairs and the private sector. OWS has selected three vaccine candidates to fund for Phase 3 trials: Moderna’s mRNA-1273, University of Oxford and AstraZeneca’s AZD1222, and Pfizer and BioNTech's BNT162. Within OWS, the US National Institutes of Health (NIH) has partnered with more than 18 biopharmaceutical companies to accelerate development of drug and vaccine candidates for COVID-19 (ACTIV). The COVID-19 Prevention Trials Network (COVPN) has also been established, which combines clinical trial networks funded by the National Institute of Allergy and Infectious Diseases (NIAID): the HIV Vaccine Trials Network (HVTN), HIV Prevention Trials Network (HPTN), Infectious Diseases Clinical Research Consortium (IDCRC), and the AIDS Clinical Trials Group.

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

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x18666210629103117 ◽

2021 ◽

Vol 18 ◽

Author(s):

Sunil Tekale ◽

Vishnu Gore ◽

Pravin Kendrekar ◽

Shivaji Thore ◽

László Kótai ◽

...

Keyword(s):

Clinical Trials ◽

Vaccine Development ◽

Transmission Rate ◽

Antiviral Treatment ◽

Drug Repurposing ◽

Current Medical ◽

Medical Emergency ◽

Global Pandemic ◽

Global Issue ◽

The City

: 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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Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

10.31222/osf.io/78mbt ◽

2020 ◽

Author(s):

Sanaa Bardaweel

Keyword(s):

Clinical Trials ◽

Drug Discovery ◽

Antimalarial Drug ◽

Drug Repurposing ◽

Spike Protein ◽

Diabetic Patients ◽

Potential Drug ◽

Chemokine Production ◽

Drug Discovery And Development ◽

Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

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Animal and Human Vaccines against West Nile Virus

Pathogens ◽

10.3390/pathogens9121073 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1073

Author(s):

Juan-Carlos Saiz

Keyword(s):

Clinical Trials ◽

West Nile Virus ◽

Vaccine Development ◽

Phase Iii ◽

West Nile ◽

Specific Therapy ◽

Phase Iii Clinical Trials ◽

Neuroinvasive Disease ◽

The Us ◽

The Status

West Nile virus (WNV) is a widely distributed enveloped flavivirus transmitted by mosquitoes, which main hosts are birds. The virus sporadically infects equids and humans with serious economic and health consequences, as infected individuals can develop a severe neuroinvasive disease that can even lead to death. Nowadays, no WNV-specific therapy is available and vaccines are only licensed for use in horses but not for humans. While several methodologies for WNV vaccine development have been successfully applied and have contributed to significantly reducing its incidence in horses in the US, none have progressed to phase III clinical trials in humans. This review addresses the status of WNV vaccines for horses, birds, and humans, summarizing and discussing the challenges they face for their clinical advance and their introduction to the market.

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Principles and Challenges in anti-COVID-19 Vaccine Development

International Archives of Allergy and Immunology ◽

10.1159/000514225 ◽

2021 ◽

pp. 1-11

Author(s):

Zuzana Strizova ◽

Jitka Smetanova ◽

Jirina Bartunkova ◽

Tomas Milota

Keyword(s):

Clinical Trials ◽

Immune Responses ◽

Vaccine Development ◽

Viral Vector ◽

Health It ◽

Therapeutic Approaches ◽

Clinical Phase ◽

Adaptive Immune ◽

Limited Efficacy ◽

Safe Vaccine

The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients keeps rising in most of the European countries despite the pandemic precaution measures. The current antiviral and anti-inflammatory therapeutic approaches are only supportive, have limited efficacy, and the prevention in reducing the transmission of SARS-CoV-2 virus is the best hope for public health. It is presumed that an effective vaccination against SARS-CoV-2 infection could mobilize the innate and adaptive immune responses and provide a protection against severe forms of coronavirus disease 2019 (COVID-19) disease. As the race for the effective and safe vaccine has begun, different strategies were introduced. To date, viral vector-based vaccines, genetic vaccines, attenuated vaccines, and protein-based vaccines are the major vaccine types tested in the clinical trials. Over 80 clinical trials have been initiated; however, only 18 vaccines have reached the clinical phase II/III or III, and 4 vaccine candidates are under consideration or have been approved for the use so far. In addition, the protective effect of the off-target vaccines, such as <i>Bacillus</i> Calmette-Guérin and measles vaccine, is being explored in randomized prospective clinical trials with SARS-CoV-2-infected patients. In this review, we discuss the most promising anti-COVID-19 vaccine clinical trials and different vaccination strategies in order to provide more clarity into the ongoing clinical trials.

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Therapeutic clinical trials to combat COVID-19 pandemic in India: analysis from trial registry

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0208 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Angelika Batta ◽

Raj Khirasaria ◽

Vinod Kapoor ◽

Deepansh Varshney

Keyword(s):

Clinical Trials ◽

De Novo ◽

Treatment Options ◽

Drug Repurposing ◽

Trial Registry ◽

Therapeutic Treatment ◽

Clinical Trial Registry ◽

Clear Cut ◽

Therapeutic Trials ◽

Microsoft Office

AbstractObjectivesWith the emergence of Novel corona virus, hunt for finding a preventive and therapeutic treatment options has already begun at a rapid pace with faster clinical development programs. The present study was carried out to give an insight of therapeutic interventional trials registered under clinical trial registry of India (CTRI) for COVID-19 pandemic.MethodsAll trials registered under CTRI were evaluated using keyword “COVID” from its inception till 9th June 2020. Out of which, therapeutic interventional studies were chosen for further analysis. Following information was collected for each trial: type of therapeutic intervention (preventive/therapeutic), treatment given, no. of centers (single center/multicentric), type of institution (government/private), study design (randomized/single-blinded/double-blinded) and sponsors (Government/private). Microsoft Office Excel 2007 was used for tabulation and analysis.ResultsThe search yielded total of 205 trials, out of which, 127 (62%) trials were interventional trials. Out of these, 71 (56%) were AYUSH interventions, 36 (28.3%) tested drugs, 9 (7%) tested a nondrug intervention, rest were nutraceuticals and vaccines. About 66 (56%) were therapeutic trials. Majority were single-centered trials, i.e. 87 (73.7%). Trials were government funded in 57 (48.3%) studies. Majority were randomized controlled trials, i.e. 67 (56.8%). AYUSH preparations included AYUSH-64, Arsenic Album, SamshamaniVati etc.ConclusionsThe number of therapeutic interventional clinical trials was fair in India. A clear-cut need exists for an increase in both quantity and quality of clinical trials for COVID-19. Drug repurposing approach in all systems of medicine can facilitate prompt clinical decisions at lower costs than de novo drug development.

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In silico imaging clinical trials: cheaper, faster, better, safer, and more scalable

Trials ◽

10.1186/s13063-020-05002-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aldo Badano

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Medical Devices ◽

In Silico ◽

Lessons Learned ◽

Patient Access ◽

High Quality ◽

Virtual Imaging ◽

Regulatory Evaluation

AbstractImaging clinical trials can be burdensome and often delay patient access to novel, high-quality medical devices. Tools for in silico imaging trials have significantly improved in sophistication and availability. Here, I describe some of the principal advantages of in silico imaging trials and enumerate five lessons learned during the design and execution of the first all-in silico virtual imaging clinical trial for regulatory evaluation (the VICTRE study).

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