Dataset Information

Old Drugs for a New Virus: Repurposed Approaches for Combating COVID-19.

ABSTRACT: There is a large global unmet need for effective countermeasures to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). The development of novel antiviral drugs is expensive and too slow to meet the immediate need. The repurposing of drugs that are approved or are under advanced clinical investigation provides a cost- and time-effective therapeutic solution. This review summarizes the major repurposed approaches that have been proposed or are already being studied in clinical trials for COVID-19. Among these approaches are drugs that aim to reduce SARS-CoV-2 replication by targeting either viral enzymatic functions or cellular factors required for the viral life cycle. Drugs that modulate the host immune response to SARS-CoV-2 infection by boosting it to enhance viral clearance or by suppressing it to prevent excessive inflammation and tissue injury represent another category. Lastly, we discuss means to discover repurposed drugs and the ongoing challenges associated with the off-label use of existing drugs in the context of the COVID-19 outbreak.

SUBMITTER: Saul S

PROVIDER: S-EPMC7416635 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Old Drugs for a New Virus: Repurposed Approaches for Combating COVID-19.

Saul Sirle S Einav Shirit S

ACS infectious diseases 20200810 9

There is a large global unmet need for effective countermeasures to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). The development of novel antiviral drugs is expensive and too slow to meet the immediate need. The repurposing of drugs that are approved or are under advanced clinical investigation provides a cost- and time-effective therapeutic solution. This review summarizes the major repurposed approaches that ha ...[more]

PMID: 32687696

Similar Datasets

Project description:A new strain of coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic was first detected in the city of Wuhan in Hubei province, China in late December 2019. To date, more than 1 million deaths and nearly 57 million confirmed cases have been recorded across 220 countries due to COVID-19, which is the greatest threat to global public health in our time. Although SARS-CoV-2 is genetically similar to other coronaviruses, i.e., SARS and Middle East respiratory syndrome coronavirus (MERS-CoV), no confirmed therapeutics are yet available against COVID-19, and governments, scientists, and pharmaceutical companies worldwide are working together in search for effective drugs and vaccines. Repurposing of relevant therapies, developing vaccines, and using bioinformatics to identify potential drug targets are strongly in focus to combat COVID-19. This review deals with the pathogenesis of COVID-19 and its clinical symptoms in humans including the most recent updates on candidate drugs and vaccines. Potential drugs (remdesivir, hydroxychloroquine, azithromycin, dexamethasone) and vaccines [mRNA-1273; measles, mumps and rubella (MMR), bacille Calmette-Guérin (BCG)] in human clinical trials are discussed with their composition, dosage, mode of action, and possible release dates according to the trial register of US National Library of Medicines (clinicaltrials.gov), European Union (clinicaltrialsregister.eu), and Chinese Clinical Trial Registry (chictr.org.cn) website. Moreover, recent reports on in silico approaches like molecular docking, molecular dynamics simulations, network-based identification, and homology modeling are included, toward repurposing strategies for the use of already approved drugs against newly emerged pathogens. Limitations of effectiveness, side effects, and safety issues of each approach are also highlighted. This review should be useful for the researchers working to find out an effective strategy for defeating SARS-CoV-2.

Project description:Background: Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Methods: Inhibition of angiotensin-converting enzyme 2 (ACE2) caused by the spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We performed drug repositioning analysis to identify drug candidates that reverse gene expression pattern in L1000 lung cell line HCC515 treated with ACE2 inhibitor. We confirmed these drug candidates by similar bioinformatics analysis using lung tissues from patients deceased from COVID-19. We further investigated deregulated genes and pathways related to lung injury, as well as the gene-pathway-drug candidate relationships. Results: We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19. Further bioinformatics analysis shows that 12 significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues. These include signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and chemokine signaling pathways. All 12 pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares 11 of 12 pathways with COL-3 and common target genes such as RHOA. It also uniquely targets other genes related to lung injury, such as CALR and MMP14. Conclusions: This study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have potential as repurposed drugs for its treatment.

Dataset Information

Old Drugs for a New Virus: Repurposed Approaches for Combating COVID-19.

Publications

Old Drugs for a New Virus: Repurposed Approaches for Combating COVID-19.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets