COVID‐19 drug repurposing: A review of computational screening methods, clinical trials, and protein interaction assays

Wang, Xueqing; Guan, Yuanfang

doi:10.1002/med.21728

Cited by 78 publications

(45 citation statements)

References 98 publications

(185 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…The role of Nsp7, a cofactor of Nsp12 for RNA synthesis, has been highlighted by Frediansyah et al . [2]. Gordan et al .…”

Section: Introductionmentioning

confidence: 99%

“…Though the mechanism of the virus-host interaction and the possible treatment have been the subject of several hundred studies, effective and safe treatment regime or a vaccine is yet to emerge. Drug repurposing may be a possible solution for immediate treatment, and scores of drugs have been suggested from various perspectives [1,2] The drugs that could be used for the treatment of Covid-19 can be classified into three categories: Antivirals, anti-inflammatory and supporting therapies. Antiviral action can further be broadly classified into three categories [3].…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Indomethacin in Covid -19 patients

Rajan¹,

Purna

Vijayaragavan

et al. 2020

Preprint

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Background Indomethacin, a well-known non-steroidal anti-inflammatory drug (NSAID), has in addition broad spectrum anti-viral activity in the laboratory including on SARS-Cov-2 virus. This trial is to observe the likelihood of efficacy and safety of Indomethacin in treating RT-PCR positive Covid patients Materials and Methods The study was done in two groups. In the first group of the study, where mild and moderate patients were involved, Propensity Score Matching was used as a methodology to compare Indomethacin and paracetamol based treatments in addition to the standard protocol for treating covid-19 patients.. Blood chemistry was collected before and after the treatment. The patients were monitored every day for clinical parameters. In this part, a patient developing hypoxia was the end point. In the second group, severe patients admitted with hypoxia were treated with Indomethacin in addition to Remdesivir, and the end point was the requirement of mechanical ventilation/admission to ICU. Results It was observed that patients treated with Indomethacin had a reduction in the number of days to become afebrile, reduction in cough and myalgia by half compared to the paracetamol set. Only one out of 72 patients in the Indomethacin arm of the first group required supplementary oxygen while 28 of the 72 patients required supplementary oxygen in the paracetamol arm. No one in the second group deteriorated enough to require mechanical ventilation. There wea no evidence of adverse reaction to indomethacin or deterioration of renal or liver function. Conclusion Indomethacin, along with standard care, seems to provide faster symptomatic relief and prevent progression of pneumonia in Covid-19 patients. It should be considered to replace paracetamol when there is no contraindication for its use.

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Section: Introductionmentioning

confidence: 99%

“…The role of Nsp7, a cofactor of Nsp12 for RNA synthesis, has been highlighted by Frediansyah et al . [2]. Gordan et al .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and Safety of Indomethacin in Covid -19 patients

Rajan¹,

Purna

Vijayaragavan

et al. 2020

Preprint

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“…The majority of drugs currently in clinical trials for COVID-19 treatment present either antiviral or immunomodulating properties, with the aim of targeting the viral life cycle and alleviating the lung-damaging symptoms (Babaei et al, 2020;Wang and Guan). Kinases play an important role in multiple of these biological processes, and therefore, different kinase inhibitors were proposed for COVID-19 treatment (Saha et al, 2020;Weisberg et al, 2020).…”

Section: Covid-19mentioning

confidence: 99%

Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation

Serra

Fratello

Federico

et al. 2021

Preprint

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New affordable therapeutic protocols for COVID-19 are urgently needed despite the increasing number of effective vaccines and monoclonal antibodies. To this end, there is increasing attention towards computational methods for drug repositioning and de novo drug design. Here, we systematically integrated multiple data-driven computational approaches to perform virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the set of prioritized drugs, we selected a subset of representative candidates to test in human cells. Two compounds, 7-hydroxystaurosporine and bafetinib, showed synergistic antiviral effects in our in vitro experiments, and strongly inhibited viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, we extracted and prioritized the chemical substructures of the identified drugs, providing a chemical vocabulary that may help to design new effective drugs.

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“…Several potential drug molecules have been recently proposed for re-purposing based on protein-structure based algorithms (reviewed in Wang et al. [ 21 ]). The ongoing efforts by various structural biology groups worldwide are providing valuable data through online resources, as well as insights from analyses of the protein structures.…”

Section: Introductionmentioning

confidence: 99%

The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies

Waman¹,

Sen²,

Váradi³

et al. 2020

Briefings in Bioinformatics

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SARS-CoV-2 is the causative agent of COVID-19, the ongoing global pandemic. It has posed a worldwide challenge to human health as no effective treatment is currently available to combat the disease. Its severity has led to unprecedented collaborative initiatives for therapeutic solutions against COVID-19. Studies resorting to structure-based drug design for COVID-19 are plethoric and show good promise. Structural biology provides key insights into 3D structures, critical residues/mutations in SARS-CoV-2 proteins, implicated in infectivity, molecular recognition and susceptibility to a broad range of host species. The detailed understanding of viral proteins and their complexes with host receptors and candidate epitope/lead compounds is the key to developing a structure-guided therapeutic design. Since the discovery of SARS-CoV-2, several structures of its proteins have been determined experimentally at an unprecedented speed and deposited in the Protein Data Bank. Further, specialized structural bioinformatics tools and resources have been developed for theoretical models, data on protein dynamics from computer simulations, impact of variants/mutations and molecular therapeutics. Here, we provide an overview of ongoing efforts on developing structural bioinformatics tools and resources for COVID-19 research. We also discuss the impact of these resources and structure-based studies, to understand various aspects of SARS-CoV-2 infection and therapeutic development. These include (i) understanding differences between SARS-CoV-2 and SARS-CoV, leading to increased infectivity of SARS-CoV-2, (ii) deciphering key residues in the SARS-CoV-2 involved in receptor–antibody recognition, (iii) analysis of variants in host proteins that affect host susceptibility to infection and (iv) analyses facilitating structure-based drug and vaccine design against SARS-CoV-2.

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COVID‐19 drug repurposing: A review of computational screening methods, clinical trials, and protein interaction assays

Cited by 78 publications

References 98 publications

Efficacy and Safety of Indomethacin in Covid -19 patients

Efficacy and Safety of Indomethacin in Covid -19 patients

Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation

The impact of structural bioinformatics tools and resources on SARS-CoV-2 research and therapeutic strategies

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