Platycodin D for COVID-19

The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical to reduce the severity of COVID-19. However, the continuous emergence of new SARS-CoV-2 subtypes highlights the need to develop additional approaches that oppose viral infections. Targeting host factors that support virus entry, replication, and propagation provide opportunities to lower SARS-CoV-2 infection rates and improve COVID-19 outcome. This includes cellular cholesterol, which is critical for viral spike proteins to capture the host machinery for SARS-CoV-2 cell entry. Once endocytosed, exit of SARS-CoV-2 from the late endosomal/lysosomal compartment occurs in a cholesterol-sensitive manner. In addition, effective release of new viral particles also requires cholesterol. Hence, cholesterol-lowering statins, proprotein convertase subtilisin/kexin type 9 antibodies, and ezetimibe have revealed potential to protect against COVID-19. In addition, pharmacological inhibition of cholesterol exiting late endosomes/lysosomes identified drug candidates, including antifungals, to block SARS-CoV-2 infection. This review describes the multiple roles of cholesterol at the cell surface and endolysosomes for SARS-CoV-2 entry and the potential of drugs targeting cholesterol homeostasis to reduce SARS-CoV-2 infectivity and COVID-19 disease severity.

AbstractTo attain promising pharmacotherapies, researchers have applied drug repurposing (DR) techniques to discover the candidate medicines to combat the coronavirus disease 2019 (COVID-19) outbreak. Although many DR approaches have been introduced for treating different diseases, only structure-based DR (SBDR) methods can be employed as the first therapeutic option against the COVID-19 pandemic because they rely on the rudimentary information about the diseases such as the sequence of the severe acute respiratory syndrome coronavirus 2 genome. Hence, to try out new treatments for the disease, the first attempts have been made based on the SBDR methods which seem to be among the proper choices for discovering the potential medications against the emerging and re-emerging infectious diseases. Given the importance of SBDR approaches, in the present review, well-known SBDR methods are summarized, and their merits are investigated. Then, the databases and software applications, utilized for repurposing the drugs against COVID-19, are introduced. Besides, the identified drugs are categorized based on their targets. Finally, a comparison is made between the SBDR approaches and other DR methods, and some possible future directions are proposed.