May we target double‐membrane vesicles and oxysterol‐binding protein to combat SARS‐CoV‐2 infection?

On the potential role of exosomes in the COVID-19 reinfection/reactivation opportunity

“…DMV formation, regulation, and reshaping as well as the remodelling of the intracellular membranous machinery became a rich area for drug discovery, specifically against coronaviruses. Some of the compounds that can be used for targeting the DMVs as a means to combat viral infection were recently reviewed (Shahmohamadnejad et al., 2020 ). The authors first considered several compounds, such as K22, oxysterol-binding protein (OSBP), OSW-1, T-00127-HEV-2, and TTP-8307, that can be used to fight against many positive sense RNA viruses by working on their Nsp proteins, and then recommended to use OSBP against SARS-CoV-2 (Shahmohamadnejad et al., 2020 ).…”

“…Some of the compounds that can be used for targeting the DMVs as a means to combat viral infection were recently reviewed (Shahmohamadnejad et al., 2020 ). The authors first considered several compounds, such as K22, oxysterol-binding protein (OSBP), OSW-1, T-00127-HEV-2, and TTP-8307, that can be used to fight against many positive sense RNA viruses by working on their Nsp proteins, and then recommended to use OSBP against SARS-CoV-2 (Shahmohamadnejad et al., 2020 ). Recently it was pointed out that the single-membrane vesicles that appear at the early stages of viral infection and some of which seem to be embedded in the ER clearly resemble nascent lipid droplets (LDs), which are the membrane-enclosed organelles that are formed by the progressive nucleation of non-polar lipids, such as triacylglycerols and steryl esters, within the hydrophobic core of the ER bilayer (Moriel-Carretero, 2020 ).…”

Drug discovery and development targeting the life cycle of SARS-CoV-2

“…Inhibitors of these three NSPs may be capable of preventing DMV formation and thus impairing viral RNA synthesis. A pre-clinical drug named K22 was reported to impair DMV formation and viral RNA synthesis of a broad range of coronaviruses including SARS-CoV and MERS-CoV by interacting with NSP6 [ 92 , 93 ]. Studies are required to explore the inhibitory effect of K22 on RNA synthesis of SARS-CoV-2.…”

Bis(monoacylglycero)phosphate, an important actor in the host endocytic machinery hijacked by SARS-CoV-2 and related viruses

“…Itraconazole (ITZ) and OSW-1 interact with OSBP and ORP4 disrupting OSBP lipid-shuttling function [ 114 ]. TTP-8307 inhibits directly the OSBP-dependent activities [ 116 ]. ORP1L, ORP5 and ORP 6, localized to LE membrane, mediate cholesterol transfer from LE to ER [ [89] , [90] , [91] ] and could be implicated in virus replication [ 118 ].…”

“…Other viruses, as picornavirus encephalomyocarditis virus and HCV, which activities are OSBP-dependent, are sensitive to TTP-8307. Very recently, OSBP was hypothesized as a potential target to SARS-CoV-2 infection [ 116 ] ( Fig. 3 B).…”