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1.
Int J Mol Sci ; 23(7)2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1776247

ABSTRACT

In a recent paper, we proposed the folding interdiction target region (FITR) strategy for therapeutic drug design in SARS-CoV-2. This paper expands the application of the FITR strategy by proposing therapeutic drug design approaches against Ebola virus disease and influenza A. We predict target regions for folding interdicting drugs on correspondingly relevant structural proteins of both pathogenic viruses: VP40 of Ebola, and matrix protein M1 of influenza A. Identification of the protein targets employs the sequential collapse model (SCM) for protein folding. It is explained that the model predicts natural peptide candidates in each case from which to start the search for therapeutic drugs. The paper also discusses how these predictions could be tested, as well as some challenges likely to be found when designing effective therapeutic drugs from the proposed peptide candidates. The FITR strategy opens a potential new avenue for the design of therapeutic drugs that promises to be effective against infectious diseases.


Subject(s)
COVID-19 , Ebolavirus , Hemorrhagic Fever, Ebola , Influenza, Human , Drug Development , Ebolavirus/metabolism , Hemorrhagic Fever, Ebola/drug therapy , Humans , Influenza, Human/drug therapy , Protein Folding , SARS-CoV-2 , Viral Matrix Proteins/metabolism
2.
Nihon Yakurigaku Zasshi ; 157(1): 31-37, 2022.
Article in Japanese | MEDLINE | ID: covidwho-1609118

ABSTRACT

Remdesivir is a direct-acting antiviral agent that inhibits viral RNA synthesis developed by Gilead Sciences, Inc. in the United States. It has been shown to have antiviral activity against single-stranded RNA viruses, including coronaviruses, in cell culture systems and animal models, and has been developed as a therapeutic agent for Ebola virus infection since 2015. however, to date, it has not been approved in any country. A novel coronavirus infection (COVID-19) was identified in Wuhan, Hubei Province, China in Dec, 2019, and is a respiratory disease characterized by fever, cough, and dyspnea. In severe cases, it may cause serious pneumonia, multi-organ failure and death. Gilead Sciences, Inc. U.S. embarked on the development of COVID-19 as a therapeutic drug, using remdesivir, which has shown in vitro and in vivo antiviral activities against MERS-CoV and SARS-CoV, which are single-stranded RNA coronaviruses that cause Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). The in vitro antiviral activity of remdesivir against SARS-CoV-2, which causes COVID-19, was confirmed and clinical studies were initiated in February 2020. Based on the results of clinical studies conducted by the National Institute of Allergy and Infectious Diseases (NIAID) and Gilead Sciences, Inc. and experience of administration from a compassionate use, an exceptional approval system based on the "Pharmaceuticals and Medical Devices Act" was also approved in Japan as of May 7, 2020 for the indication of "infections caused by SARS-CoV-2." In this article, the background of the development and clinical results of remdesivir are described.


Subject(s)
COVID-19 , Hemorrhagic Fever, Ebola , Hepatitis C, Chronic , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Hemorrhagic Fever, Ebola/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , SARS-CoV-2
3.
Antimicrob Agents Chemother ; 65(7): e0139020, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1486475

ABSTRACT

We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The copper and copper-nickel surfaces inactivated 99.9% of Ebola and Marburg viruses after 30 min, and the copper surfaces inactivated 99% of SARS-CoV-2 in 2 h. These data reveal that Ebola virus, Marburg virus, and SARS-CoV-2 are inactivated by exposure to copper ions, validating Luminore CopperTouch as an efficacious tool for infection control.


Subject(s)
COVID-19 , Ebolavirus , Hemorrhagic Fever, Ebola , Marburgvirus , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/prevention & control , Humans , SARS-CoV-2
5.
Sci Rep ; 11(1): 19458, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1447326

ABSTRACT

Efficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Ebolavirus/drug effects , Hemorrhagic Fever, Ebola/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/pharmacology , Administration, Intravenous , Aerosols , Alanine/administration & dosage , Alanine/pharmacology , Animals , Antiviral Agents/administration & dosage , Disease Models, Animal , Female , Hemorrhagic Fever, Ebola/blood , Kaplan-Meier Estimate , Liver/drug effects , Liver/virology , Lung/pathology , Lung/virology , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymph Nodes/virology , Macaca mulatta , Male , Random Allocation , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/virology , Viral Load/drug effects , Viremia/drug therapy
6.
Front Immunol ; 12: 721328, 2021.
Article in English | MEDLINE | ID: covidwho-1435991

ABSTRACT

The unprecedented 2013-2016 West Africa Ebola outbreak accelerated several medical countermeasures (MCMs) against Ebola virus disease (EVD). Several investigational products (IPs) were used throughout the outbreak but were not conclusive for efficacy results. Only the Randomized Controlled Trial (RCT) on ZMapp was promising but inconclusive. More recently, during the second-largest Ebola outbreak in North Kivu and Ituri provinces, Democratic Republic of the Congo (DRC), four IPs, including one small molecule (Remdesivir), two monoclonal antibody (mAb) cocktails (ZMapp and REGN-EB3) and a single mAb (mAb114), were evaluated in an RCT, the Pamoja Tulinde Maisha (PALM) study. Two products (REGN-EB3 and mAb114) demonstrated efficacy as compared to the control arm, ZMapp. There were remarkably few side effects recorded in the trial. The FDA approved both medications in this scientifically sound study, marking a watershed moment in the field of EVD therapy. These products can be produced relatively inexpensively and can be stockpiled. The administration of mAbs in EVD patients appears to be safe and effective, while several critical knowledge gaps remain; the impact of early administration of Ebola-specific mAbs on developing a robust immune response for future Ebola virus exposure is unknown. The viral mutation escape, leading to resistance, presents a potential limitation for single mAb therapy; further improvements need to be explored. Understanding the contribution of Fc-mediated antibody functions such as antibody-dependent cellular cytotoxicity (ADCC) of those approved mAbs is still critical. The potential merit of combination therapy and post-exposure prophylaxis (PEP) need to be demonstrated. Furthermore, the PALM trial has accounted for 30% of mortality despite the administration of specific treatments. The putative role of EBOV soluble Glycoprotein (sGP) as a decoy to the immune system, the virus persistence, and relapses might be investigated for treatment failure. The development of pan-filovirus or pan-species mAbs remains essential for protection. The interaction between FDA-approved mAbs and vaccines remains unclear and needs to be investigated. In this review, we summarize the efficacy and safety results of the PALM study and review current research questions for the further development of mAbs in pre-exposure or emergency post-exposure use.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , Ebolavirus/drug effects , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/virology , Animals , Antibodies, Monoclonal/pharmacology , Antigens, Viral/immunology , Antiviral Agents/pharmacology , Clinical Studies as Topic , Drug Approval , Drug Evaluation, Preclinical , Ebola Vaccines , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/prevention & control , Humans , Prognosis , Treatment Failure , Treatment Outcome , United States , United States Food and Drug Administration , Vaccination
7.
Antimicrob Agents Chemother ; 65(10): e0111721, 2021 09 17.
Article in English | MEDLINE | ID: covidwho-1416578

ABSTRACT

Remdesivir is a nucleoside monophosphoramidate prodrug that has been FDA approved for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of remdesivir for COVID-19 remains contentious, as several trials have not found statistically significant differences in either time to clinical improvement or mortality between remdesivir-treated and control groups. Similarly, the inability of remdesivir to provide a clinically significant benefit above other investigational agents in patients with Ebola contrasts with strong, curative preclinical data generated in rhesus macaque models. For both COVID-19 and Ebola, significant discordance between the robust preclinical data and remdesivir's lackluster clinical performance have left many puzzled. Here, we critically evaluate the assumptions of the models underlying remdesivir's promising preclinical data and show that such assumptions overpredict efficacy and minimize toxicity of remdesivir in humans. Had the limitations of in vitro drug efficacy testing and species differences in drug metabolism been considered, the underwhelming clinical performance of remdesivir for both COVID-19 and Ebola would have been fully anticipated.


Subject(s)
COVID-19 , Hemorrhagic Fever, Ebola , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Hemorrhagic Fever, Ebola/drug therapy , Humans , Macaca mulatta , SARS-CoV-2 , Treatment Outcome
8.
Immunol Res ; 69(5): 457-460, 2021 10.
Article in English | MEDLINE | ID: covidwho-1345195

ABSTRACT

In this manuscript, COVID-19, Ebola virus disease, Nipah virus infection, SARS, and MERS are suggested to be considered for a novel immunological reclassification as acute onset immune dysrhythmia syndrome (n-AIDS) due to altered monocytic, Th1/Th2, as well as cytokines and chemokines balances. n-AIDs is postulated to be the cause of the acute respiratory distress and multi-inflammatory syndromes which are described with fatal COVID-19, and immunomodulators are suggested to effectively manage the mentioned diseases as well as for other disorders caused by Th1/Th2 imbalance. Meanwhile, para COVID syndrome is suggested to describe various immune-related complications, whether before or after recovery, and to embrace a potential of a latent infection, that might be discovered later, as occurred with Ebola virus disease. Finally, our hypothesis has evolved out of our real-life practice that uses immunomodulatory drugs to manage COVID-19 safely and effectively.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Hemorrhagic Fever, Ebola/immunology , Henipavirus Infections/immunology , Acquired Immunodeficiency Syndrome/immunology , COVID-19/drug therapy , Chemokines/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Hemorrhagic Fever, Ebola/drug therapy , Henipavirus Infections/drug therapy , Humans , Immunologic Factors/therapeutic use , Lymphocytes/immunology , SARS-CoV-2/physiology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/immunology
9.
Genes (Basel) ; 12(7)2021 06 29.
Article in English | MEDLINE | ID: covidwho-1288843

ABSTRACT

This study builds a coronavirus knowledge graph (KG) by merging two information sources. The first source is Analytical Graph (AG), which integrates more than 20 different public datasets related to drug discovery. The second source is CORD-19, a collection of published scientific articles related to COVID-19. We combined both chemo genomic entities in AG with entities extracted from CORD-19 to expand knowledge in the COVID-19 domain. Before populating KG with those entities, we perform entity disambiguation on CORD-19 collections using Wikidata. Our newly built KG contains at least 21,700 genes, 2500 diseases, 94,000 phenotypes, and other biological entities (e.g., compound, species, and cell lines). We define 27 relationship types and use them to label each edge in our KG. This research presents two cases to evaluate the KG's usability: analyzing a subgraph (ego-centered network) from the angiotensin-converting enzyme (ACE) and revealing paths between biological entities (hydroxychloroquine and IL-6 receptor; chloroquine and STAT1). The ego-centered network captured information related to COVID-19. We also found significant COVID-19-related information in top-ranked paths with a depth of three based on our path evaluation.


Subject(s)
COVID-19 , Knowledge Bases , COVID-19/epidemiology , COVID-19/etiology , Chloroquine/pharmacology , Computer Graphics , Databases, Factual , Hemorrhagic Fever, Ebola/drug therapy , Humans , Hydroxychloroquine/pharmacology , Pattern Recognition, Automated , Peptidyl-Dipeptidase A/genetics , PubMed , Receptors, Interleukin-6/blood , SARS-CoV-2 , STAT1 Transcription Factor
10.
Antimicrob Agents Chemother ; 65(7): e0139020, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1276882

ABSTRACT

We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The copper and copper-nickel surfaces inactivated 99.9% of Ebola and Marburg viruses after 30 min, and the copper surfaces inactivated 99% of SARS-CoV-2 in 2 h. These data reveal that Ebola virus, Marburg virus, and SARS-CoV-2 are inactivated by exposure to copper ions, validating Luminore CopperTouch as an efficacious tool for infection control.


Subject(s)
COVID-19 , Ebolavirus , Hemorrhagic Fever, Ebola , Marburgvirus , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/prevention & control , Humans , SARS-CoV-2
11.
Nucleic Acids Res ; 49(W1): W174-W184, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1249328

ABSTRACT

Combinatorial therapies that target multiple pathways have shown great promises for treating complex diseases. DrugComb (https://drugcomb.org/) is a web-based portal for the deposition and analysis of drug combination screening datasets. Since its first release, DrugComb has received continuous updates on the coverage of data resources, as well as on the functionality of the web server to improve the analysis, visualization and interpretation of drug combination screens. Here, we report significant updates of DrugComb, including: (i) manual curation and harmonization of more comprehensive drug combination and monotherapy screening data, not only for cancers but also for other diseases such as malaria and COVID-19; (ii) enhanced algorithms for assessing the sensitivity and synergy of drug combinations; (iii) network modelling tools to visualize the mechanisms of action of drugs or drug combinations for a given cancer sample and (iv) state-of-the-art machine learning models to predict drug combination sensitivity and synergy. These improvements have been provided with more user-friendly graphical interface and faster database infrastructure, which make DrugComb the most comprehensive web-based resources for the study of drug sensitivities for multiple diseases.


Subject(s)
Algorithms , Databases, Factual , Drug Evaluation, Preclinical , Drug Therapy, Combination , Internet , COVID-19/drug therapy , Data Visualization , Datasets as Topic , Drug Synergism , Hemorrhagic Fever, Ebola/drug therapy , Humans , Machine Learning , Malaria/drug therapy , Neoplasms/drug therapy
12.
Antimicrob Agents Chemother ; 65(7): e0139020, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1203932

ABSTRACT

We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The copper and copper-nickel surfaces inactivated 99.9% of Ebola and Marburg viruses after 30 min, and the copper surfaces inactivated 99% of SARS-CoV-2 in 2 h. These data reveal that Ebola virus, Marburg virus, and SARS-CoV-2 are inactivated by exposure to copper ions, validating Luminore CopperTouch as an efficacious tool for infection control.


Subject(s)
COVID-19 , Ebolavirus , Hemorrhagic Fever, Ebola , Marburgvirus , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/prevention & control , Humans , SARS-CoV-2
13.
Viruses ; 13(4)2021 04 13.
Article in English | MEDLINE | ID: covidwho-1187060

ABSTRACT

The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.


Subject(s)
Antiviral Agents/pharmacology , Nucleosides/analogs & derivatives , Nucleosides/pharmacology , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amides , Animals , Antiviral Agents/chemistry , COVID-19/drug therapy , Hemorrhagic Fever, Ebola/drug therapy , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Mutagenesis , Pyrazines , Ribavirin , SARS-CoV-2 , Virus Replication/drug effects , Zika Virus/drug effects , Zika Virus Infection/drug therapy
14.
Biochem Biophys Res Commun ; 538: 145-150, 2021 01 29.
Article in English | MEDLINE | ID: covidwho-1125103

ABSTRACT

Human coronaviruses (HCoV) were discovered in the 1960s and were originally thought to cause only mild upper respiratory tract diseases in immunocompetent hosts. This view changed since the beginning of this century, with the 2002 SARS (severe acute respiratory syndrome) epidemic and the 2012 MERS (Middle East respiratory syndrome) outbreak, two zoonotic infections that resulted in mortality rates of approximately 10% and 35%, respectively. Despite the importance of these pathogens, no approved antiviral drugs for the treatment of human coronavirus infections became available. However, remdesivir, a nucleotide analogue prodrug originally developed for the treatment of Ebola virus, was found to inhibit the replication of a wide range of human and animal coronaviruses in vitro and in preclinical studies. It is therefore not surprising that when the highly pathogenic SARS-CoV-2 coronavirus emerged in late 2019 in China, causing global health concern due to the virus strong human-to-human transmission ability, remdesivir was one of the first clinical candidates that received attention. After in vitro studies had shown its antiviral activity against SARS-CoV-2, and a first patient was successfully treated with the drug in the USA, a number of trials on remdesivir were initiated. Several had encouraging results, particularly the ACTT-1 double blind, randomized, and placebo controlled trial that has shown shortening of the time to recovery in hospitalized patients treated with remdesivir. The results of other trials were instead negative. Here, we provide an overview of remdesivir discovery, molecular mechanism of action, and initial and current clinical studies on its efficacy.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents , COVID-19/drug therapy , Drug Discovery , Hemorrhagic Fever, Ebola/drug therapy , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/isolation & purification , Adenosine Monophosphate/therapeutic use , Alanine/chemistry , Alanine/isolation & purification , Alanine/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Antiviral Agents/therapeutic use , Humans
16.
Clin Microbiol Rev ; 34(1)2020 12 16.
Article in English | MEDLINE | ID: covidwho-962931

ABSTRACT

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Hemorrhagic Fever, Ebola/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Adenosine Monophosphate/pharmacokinetics , Adenosine Monophosphate/pharmacology , Alanine/pharmacokinetics , Alanine/pharmacology , Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Betacoronavirus/pathogenicity , COVID-19 , Clinical Trials as Topic , Compassionate Use Trials/methods , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Administration Schedule , Ebolavirus/drug effects , Ebolavirus/growth & development , Ebolavirus/pathogenicity , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/pathology , Hemorrhagic Fever, Ebola/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/growth & development , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Patient Safety , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/growth & development , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Survival Analysis , Treatment Outcome
19.
Rev Med Virol ; 30(6): 1-13, 2020 11.
Article in English | MEDLINE | ID: covidwho-688978

ABSTRACT

Since the emergence of coronavirus disease 2019 (Covid-19), many studies have been performed to characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and find the optimum way to combat this virus. After suggestions and assessments of several therapeutic options, remdesivir (GS-5734), a direct-acting antiviral drug previously tested against Ebola virus disease, was found to be moderately effective and probably safe for inhibiting SARS-CoV-2 replication. Finally, on 1 May 2020, remdesivir (GS-5734) was granted emergency use authorization as an investigational drug for the treatment of Covid-19 by the Food and Drug Administration. However, without a doubt, there are challenging days ahead. Here, we provide a review of the latest findings (based on preprints, post-prints, and news releases in scientific websites) related to remdesivir efficacy and safety for the treatment of Covid-19, along with covering remdesivir history from bench-to-bedside, as well as an overview of its mechanism of action. In addition, active clinical trials, as well as challenging issues related to the future of remdesivir in Covid-19, are covered. Up to the date of writing this review (19 May 2020), there is one finished randomized clinical trial and two completed non-randomized studies, in addition to some ongoing studies, including three observational studies, two expanded access studies, and seven active clinical trials registered on the clinicaltrials.gov and isrctn.com websites. Based on these studies, it seems that remdesivir could be an effective and probably safe treatment option for Covid-19. However, more randomized controlled studies are required.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/virology , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/pharmacology , Alanine/therapeutic use , Clinical Trials as Topic , Ebolavirus/drug effects , Ebolavirus/physiology , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Treatment Outcome , Virus Replication/drug effects
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