RESUMEN
BACKGROUND: In the last few years in silico tools, including drug repurposing coupled with structure-based virtual screening, have been extensively employed to look for anti-COVID-19 agents. OBJECTIVE: The present review aims to provide readers with a portrayal of computational approaches that could conduct more quickly and cheaply to novel anti-viral agents. Particular attention is given to docking-based virtual screening. METHOD: The World Health Organization website was consulted to gain the latest information on SARS-CoV-2, its novel variants and their interplay with COVID-19 severity and treatment options. The Protein Data Bank was explored to look for 3D coordinates of SARS-CoV-2 proteins in their free and bound states, in the wild-types and mutated forms. Recent literature related to in silico studies focused on SARS-CoV-2 proteins was searched through PubMed. RESULTS: A large amount of work has been devoted thus far to computationally targeting viral entry and searching for inhibitors of the S-protein/ACE2 receptor complex. Another large area of investigation is linked to in silico identification of molecules able to block viral proteases -including Mpro- thus avoiding maturation of proteins crucial for virus life cycle. Such computational studies have explored the inhibitory potential of the most diverse molecule databases (including plant extracts, dietary compounds, FDA approved drugs). CONCLUSION: More efforts need to be dedicated in the close future to experimentally validate the therapeutic power of in silico identified compounds in order to catch, among the wide ensemble of computational hits, novel therapeutics to prevent and/or treat COVID-19.
RESUMEN
BACKGROUND: COVID-19 has brought the world to its knees, and there is an urgent need for new strategies to identify molecules capable of fighting the pandemic. During the last few decades, NMR (Nuclear Magnetic Resonance) spectroscopy has emerged as an intriguing structural biology instrument in the antiviral drug discovery field. OBJECTIVE: The review highlights how a variety of NMR-based tools can be employed to better understand viral machineries, develop anti-viral agents and set-up diagnostic and therapeutic routes. METHODS: Works summarized herein were searched through PubMed database and the Web. RESULTS: The review focuses on a subset of human viruses that have been largely studied through NMR techniques. Indeed, NMR solid- or solution-state methodologies allow to gain structural information on viral proteins and viral genomes either in isolation or bound to diverse binding partners. NMR data can be employed to set up structure-based approaches to design efficient antiviral agents inhibiting crucial steps of viral life cycle. In addition, NMR-based metabolomics analyses of biofluids from virus-infected patients let identify metabolites biomarkers of the disease and follow changes in metabolic profiles associated with antiviral therapy thus paving the way for novel diagnostic and therapeutic approaches. CONCLUSION: Considering the NMR-based work conducted on different viruses, we believe that in the near future, much more NMR efforts will be devoted to discovering novel anti SARS-CoV-2 agents.