Sphingolipids: Effectors and Achilles Heals in Viral Infections?

Abstract

As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.

COVID-19 and its clinical severity are associated with alterations of plasma sphingolipids and enzyme activities of sphingomyelinase and ceramidase

“…Interestingly, an antiviral effect of FIASMAs against SARS-CoV, Middle East Respiratory Syndrome (MERS)-CoV and also especially SARS-CoV-2 has been demonstrated by various approaches in silico, in vitro and in vivo as summarized in recent reviews (Kornhuber et al 2021;Le Corre and Loas 2021) (Loas and Le Corre 2021). SARS-CoV-2 is thought to activate the ASM/Cer system, resulting in the formation of Cer-enriched membrane domains (Carpinteiro et al 2020) (Schneider-Schaulies et al 2021) and clustering of angiotensin-converting enzyme 2 (ACE2), the cellular receptor of SARS-CoV-2. This in turn facilitates viral entry and infection and consequently the release of proinflammatory cytokines (Tornquist et al 2021).…”

The Curious Case of Earthworms and COVID-19

“…COVID-19 research covers a wide range of specific internal infection (and infection countering) mechanisms, and/or corona viral entry points [16][17][18][19][20][21][22][23]. However, it has long been realized that a weak point of enveloped viruses may be the lipid layer, e.g., of the SARS-CoV-2 envelope [24]. The targeting of viral lipids or host lipids required for viral assembly may represent an effective virucidal approach to develop new anti-viral drugs [25][26][27].…”

Exploring SK/S1P/S1PR pathway as a target for antiviral drug development

“…The S1P receptors are key factors in vascular protection against endotheliosis. [6] The SK1/S1P axis has significant roles in the production of a pro-inflammatory response, immunomodulation, and control of vascular integrity. The SK1/S1P axis going to be an attractive target for development of drug candidates for treatment of cancer and inflammatory disorders.…”