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Race to arsenal COVID-19 therapeutics: Current alarming status and future directions.

ABSTRACT: The on-going pandemic of COVID-19 wreaked by a viral infection of SARS-CoV-2, has generated a catastrophic plight across the globe. Interestingly, one of the hallmarks of COVID-19 is the so-called 'cytokine storm' due to attack of SARS-Cov-2 in the lungs. Considering, mesenchymal stem cells (MSCs) therapy could contribute against SARS-CoV-2 viruses attack because of their immune modulatory and anti-inflammatory ability linked to their stemness, to the arsenal of treatments for COVID-19. Another novel therapeutic strategies include the blockade of rampant generation of pro-inflammatory mediators like acute respiratory distress syndrome (ARDS), degradation of viral protein capsids by PROTACs, composed of Ubiquitin-proteasome framework, and ubiquitination-independent pathway directing the SARS-CoV-2 nucleocapsid protein (nCoV N) and proteasome activator (PA28γ), etc. This review is consequently an endeavour to highlight the several aspects of COVID-19 with incorporation of important treatment strategies discovered to date and putting the real effort on the future directions to put them into the perspective.

SUBMITTER: Dubey AK

PROVIDER: S-EPMC7588316 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Race to arsenal COVID-19 therapeutics: Current alarming status and future directions.

Dubey Ankit Kumar AK Singh Aakansha A Prakash Shardendu S Kumar Manoj M Singh Ashok K AK

Chemico-biological interactions 20201027

The on-going pandemic of COVID-19 wreaked by a viral infection of SARS-CoV-2, has generated a catastrophic plight across the globe. Interestingly, one of the hallmarks of COVID-19 is the so-called 'cytokine storm' due to attack of SARS-Cov-2 in the lungs. Considering, mesenchymal stem cells (MSCs) therapy could contribute against SARS-CoV-2 viruses attack because of their immune modulatory and anti-inflammatory ability linked to their stemness, to the arsenal of treatments for COVID-19. Another ...[more]

PMID: 33121920

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Project description:The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a 'cytokine storm', during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or 'combination therapy' in patients with COVID-19 with various comorbidities, could cause drug-drug interactions, thus worsening the disease condition. Genetic variability or polymorphism in CYP2C9 across different ethnicities could contribute to COVID-19 susceptibility. A number of drugs used in patients with COVID-19 are inducers or inhibitors of, or are metabolised by, CYP2C9, and co-administration might cause pharmacokinetic and pharmacodynamic interactions. It is also worth mentioning that some of the COVID-19 drug interactions are due to altered activity of other CYPs including CYP3A4. Isoniazid/rifampin for COVID-19 and tuberculosis co-infection; lopinavir/ritonavir and cobicistat/remdesivir combination therapy; or multi-drug therapy including ivermectin, azithromycin, montelukast and acetylsalicylic acid, known as TNR4 therapy, all improved recovery in patients with COVID-19. However, a combination of CYP2C9 inducers, inhibitors or both, and plausibly different CYP isoforms could lead to treatment failure, hepatotoxicity or serious side effects including thromboembolism or bleeding, as observed in the combined use of azithromycin/warfarin. Further, herbs that are CYP2C9 inducers and inhibitors, showed anti-COVID-19 properties, and in silico predictions postulated that phytochemical compounds could inhibit SARS-CoV-2 virus particles. COVID-19 vaccines elicit immune responses that activate cytokine release, which in turn suppresses CYP expression that could be the source of compromised CYP2C9 drug metabolism and the subsequent drug-drug interaction. Future studies are recommended to determine CYP regulation in COVID-19, while recognising the involvement of CYP2C9 and possibly utilising CYP2C9 as a target gene to tackle the ever-mutating SARS-CoV-2.

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Race to arsenal COVID-19 therapeutics: Current alarming status and future directions.

Publications

Race to arsenal COVID-19 therapeutics: Current alarming status and future directions.

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