Remdesivir: A Review of Its Discovery and Development Leading to Human Clinical Trials for Treatment of COVID-19

Rt, Eastman; Js, Roth; Kr, Brimacombe; Simeonov, Anton; Shen, Mingwang; Patnaik, Sibabratta; Hall, '

doi:10.20944/preprints202004.0299.v1

Cited by 17 publications

(19 citation statements)

References 57 publications

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“…Remdesivir suppresses viral replication and it was initially tested in clinical trials to prevent the 2014 Ebola outbreak. Later investigations indicated Remdesivir's ability to inhibit replication of coronavirus, including SARS-CoV-2 as well [32]. In another cohort study, medical progress was observed in 68% of patients taken to the hospital with severe COVID-19 treated with Remdesivir [33].…”

Section: Rna-dependent Rna Polymerase Inhibitorsmentioning

confidence: 99%

Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking

Alizadehmohajer

Sadeghi

Najafgholian

et al. 2020

Preprint

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Background: 2019-nCoV (COVID-19) is a pandemic disease with a high infectivity and mortality. The prevention and treatment of COVID-19 have become urgent matters for consideration. It often takes several years to develop new drugs, or vaccines, based on the usual clinical trial process. This dwell-time can be shortened by repurposing previously approved drugs.Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase We aimed to assess several available small-molecule; Abl kinase inhibitors, Janus kinase inhibitor, Dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papin-like Protease inhibitors, using binding simulation with proteins that might prove to be effective in inhibiting COVID-19 infection. The efficiency of inhibitors was evaluated based on docking scores using auto dock vina software.Results: Strong ligand-protein interactions were predicted among some of these drugs, such as Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control (directly and indirectly) or in viral proteins attenuation. It is worth to highlight the powerful immunomodulatory role of Abivertinib that inhibits pro-inflammatory cytokine production that are associated with cytokine release syndrome (CRS) or cytokine storm and progression of COVID-19 infection.Conclusions: COVID-19 is similar to SARS-CoV, the potential role of Abl kinase inhibitors such as Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS) may indicate that these drugs may be useful for COVID-19. Moreover, Remdesivir, and Telaprevir have the most efficiency with their docked proteins in-silico as well although clinical trials are needed to confirm the effect of these drugs.

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Section: Rna-dependent Rna Polymerase Inhibitorsmentioning

confidence: 99%

Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking

Alizadehmohajer

Sadeghi

Najafgholian

et al. 2020

Preprint

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“…Currently, there are several clinically approved antiviral drugs under consideration to find effective treatments targeting viral entry and replications. These include an oral drug called EIDD-2801, anti-malarial drug hydroxychloroquine, remdesivir -a failed Ebola drug, and kaletra which is a combination of HIV drug lopinavir and ritonavir [22][23][24][25]. Not just anti-viral drugs, but immunosuppressants like sarilumab and tocilizumab are also being tested for the patients, where not only the virus but the patient's immune overreaction worsens the situation ultimately killing them [26].…”

Section: Potential Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19

Pinky

Gupta

Krishnakumar

et al. 2020

Stem Cell Rev and Rep

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The recent pandemic situation transpired due to coronavirus novel strain SARS-CoV-2 has become a global concern. This human coronavirus (HCov-19) has put the world on high alert as the numbers of confirmed cases are continuously increasing. The world is now fighting against this deadly virus and is leaving no stone unturned to find effective treatments through testing of various available drugs, including those effective against flu, malaria, etc. With an urgent need for the development of potential strategies, two recent studies from China using Mesenchymal Stem Cells (MSCs) to treat COVID-19 pneumonia have shed some light on a potential cure for the COVID-19 infected patients. However, MSCs, despite being used in various other clinical trials have always been questioned for their tendency to aggregate or form clumps in the injured or disease microenvironment. It has also been reported in various studies that exosomes secreted by these MSCs, contribute towards the cell's biological and therapeutic efficacy. There have been reports evaluating the safety and feasibility of these exosomes in various lung diseases, thereby proposing them as a cell-free therapeutic agent. Also, attractive features like cell targeting, low-immunogenicity, safety, and high biocompatibility distinguish these exosomes from other synthetic nano-vesicles and thus potentiate their role as a drug delivery nano-platform. Building upon these observations, herein, efforts are made to give an overview of stem cell-derived exosomes as an appealing therapeutic agent and drug delivery nano-carrier. In this review, we briefly recapitulate the recent evidence and developments in understanding exosomes as a promising candidate for novel nano-intervention in the current pandemic scenario. Furthermore, this review will highlight and discuss mechanistic role of exosomes to combat severe lung pathological conditions. We have also attempted to dwell into the nano-formulation of exosomes for its better applicability, storage, and stability thereby conferring them as off the shelf therapeutic.

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“…Potential drug candidates for COVID-19 therapy are continuously substituted and changed, similar to basketball players in the last minutes of the final game to save the championship. Remdesivir, the most awaited and most promising candidate, has been fervently supported by doctors and politicians as a potential cure for COVID-19 [129] but appears to be inefficient according to the first randomized trial (158 patients) in China on patients with severe COVID-19 symptoms [130]. In addition, it was found that a high dosage of remdesivir may induce testicular toxicity and result in deterioration of sperm parameters in mice [131].…”

Section: Post Datummentioning

confidence: 99%

COVID-19 treatment: Much research and testing, but far, few magic bullets against SARS-CoV-2 coronavirus

Kouznetsov

2020

European Journal of Medicinal Chemistry

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The new virus of the of b-Coronaviruses genus, SARS-CoV-2, is the causative agent of coronavirus disease-2019 (COVID-19) and is winning a proverbial chess match against all players simultaneous, including physicians, clinicians, pathologists, doctors, scientists, economists, athletes and politicians. The COVID-19 outbreak has seriously threatened public health, killing the most vulnerable persons and causing general panic. To stop this disease, effective remedies (i.e., drugs, vaccines, personal protection elements, etc.) are urgently required. Unfortunately, no registered specific therapies (including antiviral therapies, immune-modulating agents and vaccines) are currently available to treat coronavirus infections, highlighting an urgent need for therapeutics targeting SARS-CoV-2. In this work, fourteen existing small molecule drugs or/and experimental drugs selected by experts and examined from the point of view of bioavailability via the Lipinski-Veber rules and assessment of their physicochemical descriptors. The aim of this study is to discover selected pattern similarities and peculiar characteristics that could be useful for antiviral drug optimization, drug combination or new antiviral agent design.

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Remdesivir: A Review of Its Discovery and Development Leading to Human Clinical Trials for Treatment of COVID-19

Cited by 17 publications

References 57 publications

Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking

Screening of Potential Inhibitors of Covid-19 with Repurposing Approach Via Molecular Docking

Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19

COVID-19 treatment: Much research and testing, but far, few magic bullets against SARS-CoV-2 coronavirus

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