tetano
Editor, Senior Moderator
Heliyon
. 2022 May 11;e09387.
doi: 10.1016/j.heliyon.2022.e09387. Online ahead of print.
A Network-Biology led Computational Drug repurposing Strategy to prioritize therapeutic options for COVID-19
Pankaj Khurana[SUP] 1 [/SUP], Rajeev Varshney[SUP] 1 [/SUP], Apoorv Gupta[SUP] 1 [/SUP]
Affiliations
Abstract
The alarming pandemic situation of novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection, high drug development cost and slow process of drug discovery have made repositioning of existing drugs for therapeutics a popular alternative. It involves the repurposing of existing safe compounds which results in low overall development costs and shorter development timeline. In the present study, a computational network-biology approach has been used for comparing three candidate drugs i.e. quercetin, N-acetyl cysteine (NAC), and 2-deoxy-glucose (2-DG) to be effectively repurposed against COVID-19. For this, the associations between these drugs and genes of Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) diseases were retrieved and a directed drug-gene-gene-disease interaction network was constructed. Further, to quantify the associations between a target gene and a disease gene, the shortest paths from the target gene to the disease genes were identified. A vector DV was calculated to represent the extent to which a disease gene was influenced by these drugs. Quercetin was quantified as the best among the three drugs, suited for repurposing with DV of -70.19, followed by NAC with DV of -39.99 and 2-DG with DV of -13.71. The drugs were also assessed for their safety and efficacy balance (in terms of therapeutic index) using network properties. It was found that quercetin was a forerunner than other two drugs.
Keywords: 2 DG; Network-biology; Quercetin; n acetyl cysteine.
. 2022 May 11;e09387.
doi: 10.1016/j.heliyon.2022.e09387. Online ahead of print.
A Network-Biology led Computational Drug repurposing Strategy to prioritize therapeutic options for COVID-19
Pankaj Khurana[SUP] 1 [/SUP], Rajeev Varshney[SUP] 1 [/SUP], Apoorv Gupta[SUP] 1 [/SUP]
Affiliations
- PMID: 35578630
- PMCID: PMC9093055
- DOI: 10.1016/j.heliyon.2022.e09387
Abstract
The alarming pandemic situation of novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection, high drug development cost and slow process of drug discovery have made repositioning of existing drugs for therapeutics a popular alternative. It involves the repurposing of existing safe compounds which results in low overall development costs and shorter development timeline. In the present study, a computational network-biology approach has been used for comparing three candidate drugs i.e. quercetin, N-acetyl cysteine (NAC), and 2-deoxy-glucose (2-DG) to be effectively repurposed against COVID-19. For this, the associations between these drugs and genes of Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) diseases were retrieved and a directed drug-gene-gene-disease interaction network was constructed. Further, to quantify the associations between a target gene and a disease gene, the shortest paths from the target gene to the disease genes were identified. A vector DV was calculated to represent the extent to which a disease gene was influenced by these drugs. Quercetin was quantified as the best among the three drugs, suited for repurposing with DV of -70.19, followed by NAC with DV of -39.99 and 2-DG with DV of -13.71. The drugs were also assessed for their safety and efficacy balance (in terms of therapeutic index) using network properties. It was found that quercetin was a forerunner than other two drugs.
Keywords: 2 DG; Network-biology; Quercetin; n acetyl cysteine.