Coronavirus puts drug repurposing on the fast track

Harrison, Charlotte

doi:10.1038/d41587-020-00003-1

Cited by 416 publications

(365 citation statements)

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“…A randomized control trial of lopinavir-ritonavir, a combination protease inhibitor designed for HIV treatment, in 199 patients with at least moderate COVID-19 did not significantly alter clinical improvement or viral clearance (131). While the results of this trial were met with disappointment, this negative study should not forestall trials and drug development of protease inhibitors as a therapeutic class, given that this drug was not specifically designed for SARS-CoV2 (128).…”

Section: Protease Inhibitors -Inhibitors Of Nonstructural Protein Genmentioning

confidence: 91%

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COVID-19 for the Cardiologist

Atri

Siddiqi

Lang

et al. 2020

JACC: Basic to Translational Science

252

121

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Highlights-Severe acute respiratory virus-2 (SARS-CoV2), the infection responsible for coronavirus disease-2019 (COVID-19), has spread globally leading to a devastating loss of life. In a few short months, the clinical and scientific communities have rallied to rapidly evolve our understanding of the mechanism(s) of disease and potential therapeutics. -This review discusses the current understanding of the basis virology of SARS-CoV2 and the epidemiology, clinical manifestations, including cardiovascular, and mortality of COVID-19. A detailed review of the viral life cycle and putative mechanism(s) of injury frames the discussion of possible preventative and therapeutic strategies. -The ongoing, unprecedented collective effort will, without a doubt, advance our ability to prevent the spread and optimally care for patients suffering from COVID-19. SummaryThe coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has reached pandemic status. As it spreads across the world, it has overwhelmed healthcare systems, strangled the global economy and led to a devastating loss of life. Widespread efforts from regulators, clinicians and scientists are driving a rapid expansion of knowledge of the SARS-CoV2 virus and the COVID-19 disease.We review the most current data with a focus on our basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. We discuss the basic virology, epidemiology, clinical manifestation, multi-organ consequences, and outcomes. With a focus on cardiovascular complications, we propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.

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Section: Protease Inhibitors -Inhibitors Of Nonstructural Protein Genmentioning

confidence: 91%

“…Another nucleotide analog for the disruption of RdRp-dependent viral replication is favipiravir, which has investigational approval in several countries (128,129). Additional agents that are under study include emtricitabine/tenofovir and ribavirin (128,130).…”

Section: Nucleotide Analogs -Inhibitors Of Viral Genome Replicationmentioning

confidence: 99%

COVID-19 for the Cardiologist

Atri

Siddiqi

Lang

et al. 2020

JACC: Basic to Translational Science

252

121

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“…However, chloroquine is currently among the best available candidates to impact the severity of SARS-CoV-2 infections in humans. Currently, at least ten clinical trials are testing chloroquine as an anti-COVID-19 therapy [55].…”

Section: Cov-2 Coronavirus That Causes Covid-19 Chloroquine Repurposmentioning

confidence: 99%

New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?

Devaux

Rolain

Colson

et al. 2020

International Journal of Antimicrobial Agents

952

936

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Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.

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“…Polymerase (RdRP) inhibitor remdesivir [9][10][11] , and recent data suggests a new nucleotide analog may be effective against SARS-CoV-2 infection in laboratory animals 12 . Clinical trials on several vaccine candidates are also underway 13 , as well as trials of repurposed host-directed compounds inhibiting the human protease TMPRSS2 14 .…”

mentioning

confidence: 99%

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

Gordon¹,

Jang²,

Bouhaddou³

et al. 2020

Preprint

421

584

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ABSTRACTAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

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Coronavirus puts drug repurposing on the fast track

Cited by 416 publications

References 0 publications

COVID-19 for the Cardiologist

COVID-19 for the Cardiologist

New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

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