Scope of repurposed drugs against the potential targets of the latest variants of SARS-CoV-2

Abstract

The unprecedented outbreak of the severe acute respiratory syndrome (SARS) Coronavirus-2, across the globe, triggered a worldwide uproar in the search for immediate treatment strategies. With no specific drug and not much data available, alternative approaches such as drug repurposing came to the limelight. To date, extensive research on the repositioning of drugs has led to the identification of numerous drugs against various important protein targets of the coronavirus strains, with hopes of the drugs working against the major variants of concerns (alpha, beta, gamma, delta, omicron) of the virus. Advancements in computational sciences have led to improved scope of repurposing via techniques such as structure-based approaches including molecular docking, molecular dynamic simulations and quantitative structure activity relationships, network-based approaches, and artificial intelligence-based approaches with other core machine and deep learning algorithms. This review highlights the various approaches to repurposing drugs from a computational biological perspective, with various mechanisms of action of the drugs against some of the major protein targets of SARS-CoV-2. Additionally, clinical trials data on potential COVID-19 repurposed drugs are also highlighted with stress on the major SARS-CoV-2 targets and the structural effect of variants on these targets. The interaction modelling of some important repurposed drugs has also been elucidated. Furthermore, the merits and demerits of drug repurposing are also discussed, with a focus on the scope and applications of the latest advancements in repurposing.

The role of SARS-CoV-2 accessory proteins in immune evasion

“…Furthermore, the host's strong antibody responses to the ORF8 protein have become the primary serological indicator of SARS-CoV-2 infection for screening. Convalescent COVID-19 patients' plasma has also been found to have ORF9b-specific antibodies [1] , [2] , [3] , [4] , [5] .…”

The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial

“…Despite the development of different vaccines from Moderna and Pfizer-BioNTech and new drugs such as remdesivir and its combination with repurposed drugs such as chloroquine, hydroxychloroquine ( Younis et al, 2020 ), and ivermectin ( Wehbe et al, 2021 ; Niranjan et al, 2022 ), which act on different enzymes and proteins of SARS-CoV-2 including helicase, main protease, non-structural proteins (Nsp15 and Nsp9), RNA-dependent-RNA-polymerase, and RNA replicate, the fight against COVID-19 has not yet ended ( Alshrari et al, 2022 ; Chatterjee and Thakur 2022 ). Additionally, corticosteroids caused suppression of the excessive immunological response with the prevention of multi-organ failure and death in severe cases ( Sen et al, 2022 ).…”

Drug repurposing for viral cancers: A paradigm of machine learning, deep learning, and virtual screening‐based approaches

“…Structure‐based screening methods have contributed equally to drug repurposing efforts starting from the start of in silico 200–203 approaches such as molecular docking 204–206 . Generally, structure‐based VS ranks potential drug molecules against the protein target of interest which leads to reduction in experimental cost 114,207–209 . Thus, normally used approaches use the structure of small molecule and protein and predict the binding affinity 210–212 as shown in Figure 6A.…”