Optimizing COVID‐19 Candidate Therapeutics: Thinking Without Borders

Rayner, Craig R.; Smith, Patrick F.; Hershberger, Kevin; Wesche, David

doi:10.1111/cts.12790

Cited by 14 publications

(20 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is a human anti-interleukin-6 receptor antibody, which helps prevent lung damage and elevated levels of IL-6 during the disease. Early tests have shown that this treatment rapidly depletes circulating levels of IL-6 in the blood [79]. ChAdOx1 nCoV-19 is a vaccine currently being investigated for prophylaxis against SARS-CoV-2.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status

El-Aziz

Stockand

2020

Infection, Genetics and Evolution

316

300

View full text Add to dashboard Cite

show abstract

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status

El-Aziz

Stockand

2020

Infection, Genetics and Evolution

316

300

View full text Add to dashboard Cite

show abstract

“…At present, there are more than 200 registered clinical trials involving COVID‐19 patients 1 . Conventional drug development paradigms and trial designs do not fit well with the urgency and limited window of opportunity at the individual patient level and scale of the crisis 2 . The clinical pharmacology remit to get the right drug and indeed “the right dose in every patient” 3 has never been clearer, 4 but in the context of the COVID‐19 pandemic we need to add “as soon as possible.” Patients in greatest need may not have the time to benefit from an overly cautious approach, whereas they may also be at highest risk of experiencing exaggerated and previously unknown adverse events.…”

Section: Figurementioning

confidence: 99%

“…However, clinical pharmacologists have a wealth of knowledge about approved drugs, many of which are currently in clinical trials for repurposing. This knowledge can be harnessed and translated immediately to optimize dosing and treatment regimens: Absorption, distribution, metabolism, and pharmacokinetics; Pharmacokinetics in special populations and the role of factors such as age (including pediatrics 5 and geriatrics), gender, ethnicity, morphometry, disease, and organ function; Drug–drug interactions (DDIs): infectious diseases are often best treated with more than one drug, and several potential combination therapies have already been proposed for COVID‐19 2 . In addition, age is associated with concomitant medications, which may cause DDIs with COVID‐19 drugs, especially those commonly used in older people; Pharmacogenomics and precision medicine; Relationship between pharmacokinetics and pharmacodynamics (biomarker) response; Relationship between exposure and adverse events 6,7 …”

Section: Figurementioning

confidence: 99%

COVID‐19: A Defining Moment for Clinical Pharmacology?

Graaf

Giacomini

2020

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

“…A number of RCTs are underway to evaluate the efficacy of tocilizumab, alone or in combination, in severely ill patients with COVID-19 (10). Other anti-IL-6 receptor antibodies studied for the treatment of COVID-19 include the humanized monoclonal antibody TZLS-501, sarilumab, and the recombinant human-mouse chimeric monoclonal antibody siltuximab (75). TZLS-501 has been shown to significantly reduce circulating levels of IL-6 in the blood (75).…”

Section: Discovery Of Potential Therapeutic Agents Based On Host Immumentioning

confidence: 99%

An overview of potential therapeutic agents to treat COVID-19

Dong¹,

Tian

Shen

et al. 2020

BST

View full text Add to dashboard Cite

Since China first reported an unusual type of pneumonia on December 31, 2019, the number of people identified with this pneumonia has been increasing at an alarming rate, leading to a worldwide public health emergency. This new infectious disease, officially named coronavirus disease (COVID-19) on February 11, 2020 by the World Health Organization (WHO), is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On March 11, 2020, the COVID-19 outbreak was officially declared a pandemic by the WHO. The disease is characterized by flu-like symptoms, such as cough, fever, myalgia, and fatigue. Although some infections are asymptomatic, many patients develop pneumonia, and some patients even develop severe and fatal respiratory diseases. As noted by the WHO, a total of 32,029,704 confirmed cases and 979,212 deaths worldwide were caused by COVID-19 as of September 25, 2020 (1). Nevertheless, there are no approved vaccines or specific drugs available for the prevention and treatment of COVID-19 at this moment. Given the threat of the pandemic and urgent need for effective vaccines and antivirals, vigorous efforts are being made globally to stop the COVID-19 epidemic. Compared to de novo drug development, drug repurposing offers advantages in taking less time and involving less cost, so it may be an ideal strategy for finding and identifying effective and safe potential therapeutic agents for the disease (2). A better understanding of SARS-CoV-2 virology, the underlying mechanisms by which it attacks host cells, and the host response to the infection is crucial to drug discovery and repurposing. Like severe acute respiratory syndrome coronavirus (SARS-CoV) that emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) that was identified in 2012, SARS-CoV-2 is a lipid-enveloped, single-stranded, positive sense RNA virus that is a zoonotic β-coronavirus (3). The SARS-CoV-2 genome, first published on January 24, 2020 (4), shares a nucleotide identity of 82% with SARS-CoV (5). Studies have confirmed that SARS-CoV-2 and SARS-CoV bind to the same host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), via their structural spike glycoprotein (S protein) (6). Host transmembrane serine protease 2 (TMPRSS2), along with ACE2 and virus S protein, is responsible for virus fusion and entry, and the three have been studied as potential targets for screening therapeutic compounds and repurposing drugs (7,8). In addition, many agents have been studied and identified based on virus-specific nucleic acids or proteins such as RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease 3Clpro (also termed Mpro), and papain-like proteases (PLpro), which play an important role in virus replication

show abstract

Optimizing COVID‐19 Candidate Therapeutics: Thinking Without Borders

Cited by 14 publications

References 6 publications

Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status

Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status

COVID‐19: A Defining Moment for Clinical Pharmacology?

An overview of potential therapeutic agents to treat COVID-19

Contact Info

Product

Resources

About