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Drug repurposing and cytokine management in response to COVID-19: A review.

ABSTRACT: Coronavirus disease 2019 (COVID-19), the infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an aggressive disease that attacks the respiratory tract and has a higher fatality rate than seasonal influenza. The COVID-19 pandemic is a global health crisis, and no specific therapy or drug has been formally recommended for use against SARS-CoV-2 infection. In this context, it is a rational strategy to investigate the repurposing of existing drugs to use in the treatment of COVID-19 patients. In the meantime, the medical community is trialing several therapies that target various antiviral and immunomodulating mechanisms to use against the infection. There is no doubt that antiviral and supportive treatments are important in the treatment of COVID-19 patients, but anti-inflammatory therapy also plays a pivotal role in the management COVID-19 patients due to its ability to prevent further injury and organ damage or failure. In this review, we identified drugs that could modulate cytokines levels and play a part in the management of COVID-19. Several drugs that possess an anti-inflammatory profile in others illnesses have been studied in respect of their potential utility in the treatment of the hyperinflammation induced by SAR-COV-2 infection. We highlight a number of antivirals, anti-rheumatic, anti-inflammatory, antineoplastic and antiparasitic drugs that have been found to mitigate cytokine production and consequently attenuate the "cytokine storm" induced by SARS-CoV-2. Reduced hyperinflammation can attenuate multiple organ failure, and even reduce the mortality associated with severe COVID-19. In this context, despite their current unproven clinical efficacy in relation to the current pandemic, the repurposing of drugs with anti-inflammatory activity to use in the treatment of COVID-19 has become a topic of great interest.

SUBMITTER: Heimfarth L

PROVIDER: S-EPMC7457938 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Drug repurposing and cytokine management in response to COVID-19: A review.

Heimfarth Luana L Serafini Mairim Russo MR Martins-Filho Paulo Ricardo PR Quintans Jullyana de Souza Siqueira JSS Quintans Jullyana de Souza Siqueira JSS Quintans-Júnior Lucindo José LJ

International immunopharmacology 20200831

Coronavirus disease 2019 (COVID-19), the infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an aggressive disease that attacks the respiratory tract and has a higher fatality rate than seasonal influenza. The COVID-19 pandemic is a global health crisis, and no specific therapy or drug has been formally recommended for use against SARS-CoV-2 infection. In this context, it is a rational strategy to investigate the repurposing of existing drugs to use ...[more]

PMID: 32919216

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Project description:BackgroundSince the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in finding a potential therapeutic agent for the disease. Considering the matter of time, the computational methods of drug repurposing offer the best chance of selecting one drug from a list of approved drugs for the life-threatening condition of COVID-19. The present systematic review aims to provide an overview of studies that have used computational methods for drug repurposing in COVID-19.MethodsWe undertook a systematic search in five databases and included original articles in English that applied computational methods for drug repurposing in COVID-19.ResultsTwenty-one original articles utilizing computational drug methods for COVID-19 drug repurposing were included in the systematic review. Regarding the quality of eligible studies, high-quality items including the use of two or more approved drug databases, analysis of molecular dynamic simulation, multi-target assessment, the use of crystal structure for the generation of the target sequence, and the use of AutoDock Vina combined with other docking tools occurred in about 52%, 38%, 24%, 48%, and 19% of included studies. Studies included repurposed drugs mainly against non-structural proteins of SARS-CoV2: the main 3C-like protease (Lopinavir, Ritonavir, Indinavir, Atazanavir, Nelfinavir, and Clocortolone), RNA-dependent RNA polymerase (Remdesivir and Ribavirin), and the papain-like protease (Mycophenolic acid, Telaprevir, Boceprevir, Grazoprevir, Darunavir, Chloroquine, and Formoterol). The review revealed the best-documented multi-target drugs repurposed by computational methods for COVID-19 therapy as follows: antiviral drugs commonly used to treat AIDS/HIV (Atazanavir, Efavirenz, and Dolutegravir Ritonavir, Raltegravir, and Darunavir, Lopinavir, Saquinavir, Nelfinavir, and Indinavir), HCV (Grazoprevir, Lomibuvir, Asunaprevir, Ribavirin, and Simeprevir), HBV (Entecavir), HSV (Penciclovir), CMV (Ganciclovir), and Ebola (Remdesivir), anticoagulant drug (Dabigatran), and an antifungal drug (Itraconazole).ConclusionsThe present systematic review provides a list of existing drugs that have the potential to influence SARS-CoV2 through different mechanisms of action. For the majority of these drugs, direct clinical evidence on their efficacy for the treatment of COVID-19 is lacking. Future clinical studies examining these drugs might come to conclude, which can be more useful to inhibit COVID-19 progression.

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Drug repurposing and cytokine management in response to COVID-19: A review.

Publications

Drug repurposing and cytokine management in response to COVID-19: A review.

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