A Review of In Silico Research, SARS-CoV-2, and Neurodegeneration: Focus on Papain-Like Protease

Since the appearance of SARS-CoV-2 and the COVID-19 pandemic, the search for new approaches to treat this disease took place in the scientific community. The in silico approach has gained importance at this moment, once the methodologies used in this kind of study allow for the identification of specific protein-ligand interactions, which may serve as a filter step for molecules that can act as specific inhibitors. In addition, it is a low-cost and high-speed technology. Molecular docking has been widely used to find potential viral protein inhibitors for structural and non-structural proteins of the SARS-CoV-2, aiming to block the infection and the virus multiplication. The papain-like protease (PLpro) participates in the proteolytic processing of SARS-CoV-2 and composes one of the main targets studied for pharmacological intervention by in silico methodologies. Based on that, we performed a systematic review about PLpro inhibitors from the perspective of in silico research, including possible therapeutic molecules in relation to this viral protein. The neurological problems triggered by COVID-19 were also briefly discussed, especially relative to the similarities of neuroinflammation present in Alzheimer's disease. In this context, we focused on two molecules, curcumin and glycyrrhizinic acid, given their PLpro inhibitory actions and neuroprotective properties and potential therapeutic effects on COVID-19.

Automated summary

Since the emergence of SARS-CoV-2 and the COVID-19 pandemic, there has been a growing interest in using in silico approaches to identify potential therapeutic molecules for this disease. Molecular docking, a commonly used method, has been employed to find inhibitors for viral proteins of SARS-CoV-2, including the papain-like protease (PLpro). This systematic review focuses on in silico research of PLpro inhibitors and their potential therapeutic effects on COVID-19. Additionally, the neurological problems associated with COVID-19, particularly the similarities to neuroinflammation in Alzheimer's disease, are briefly discussed.