Strategies for drug repurposing against coronavirus targets

Abstract

Repurposing regulatory agency approved drugs and investigational compounds with known safety profiles can significantly fast track the drug development timeline over de novo drug discovery, with lower investment requirements and improved attrition rate. These advantages are vital in any epidemic or pandemic situation, where hospital beds are occupied by patients for whom there is no known treatment. Here we examine drug repurposing in the context of human coronaviruses, SARS-CoV, MERS-CoV, and, in particular, SARS-CoV-2, the virus currently causing a continued widespread pandemic with substantial impacts on public health and economy. The key druggable targets explored were those involved in viral entry, viral replication, and viral-induced ARDS, as well as viral proteases, with a focus on the strategy by which the drugs were repurposed.

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

“…In line with the different strategies for drug repurposing to target virus replication and disease/complications ( Sultana et al, 2020 ; Smith et al, 2022 ), we have previously hypothesized that p53 activator Nutlin-3, a potent and selective activator of p53 might be useful to counteract SARS-CoV-2 infection ( Zauli et al, 2020 ). Besides natural compounds with anti-inflammatory activity, other studies have directly suggested that pharmacological activation of p53 might be a strategy to counteract SARS-CoV-2 infection ( Ramaiah, 2020 ; Zauli et al, 2020 ).…”

Comparative Analysis of the Interaction between the Antiviral Drug Umifenovir and Umifenovir Encapsulated in Phospholipids Micelles (Nanosome/Umifenovir) with dsDNA as a Model for Pharmacogenomic Analysis by Electrochemical Methods

“…An indole derivative umifenovir (Arbidol, ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylsulfanyl)methyl]-1H-indole-3-carboxylate) is widely used drug for the prevention and treatment of COVID-19 and some other viral infections [2,9,30]. We have studied electrochemical behavior of Umi on the screen-printed electrodes modified with single-wall carbon nanotubes.…”

“…used drug for the prevention and treatment of COVID-19 and some other viral infections [2,9,30]. We have studied electrochemical behavior of Umi on the screen-printed electrodes modified with single-wall carbon nanotubes.…”

Virus Infection and Systemic Inflammation: Lessons Learnt from COVID-19 and Beyond

“…Main protease (Mpro or 3CLpro) and papain-like protease (PLpro) are viral proteases that are required for the replication of SARS-CoV-2. However, targeting these crucial steps by lopinavir/ritonavir and darunavir/cobicistat did not provide convincing clinical benefit in patients with COVID-19 [ 200 ]. In contrast, nirmatrelvir, an orally-administered C3-like protease inhibitor that is sold in combination with ritonavir under the brand name Paxlovid, is recommended for use in high-risk, non-hospitalized COVID-19 patients from the age of 12 within five days after symptoms onset.…”