Heparin-binding Peptides as Novel Therapies to Stop SARS-CoV-2 Cellular Entry and Infection

Abstract

Heparan Sulfate Proteoglycans (HSPGs) are cell surface receptors that are involved in the cellular uptake of pathological amyloid proteins and viruses, including the novel coronavirus; Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). Heparin and heparan sulfate antagonize the binding of these pathogens to HSPGs and stop their cellular internalization, but the anticoagulant effect of these agents has been limiting their use in the treatment of viral infections. Heparin-binding peptides (HBPs) are suitable non-anticoagulant agents that are capable to antagonize binding of heparin-binding pathogens to HSPGs. Here, we review and discuss the use of HBPs as viral uptake inhibitors and will address their benefits and limitations to treat viral infections. Furthermore, we will discuss a variant of these peptides that is in the clinic and can be considered as a novel therapy in Corona Virus Disease-2019 (COVID-19) infection. Significance Statement The need to discover treatment modalities for COVID-19 is a necessity, and therapeutic interventions such as Heparin-binding Peptides (HBPs), which are used for other cases, can be beneficial based on their mechanisms of actions. In this paper, we have discussed the application of HBPs as viral uptake inhibitors in COVID-19 and explained possible mechanisms of actions and the therapeutic effects.

Cardiovascular protective properties of oxytocin against COVID-19

“…OXT can induce the expression of extracellular superoxide dismutase [ 92 ], an antioxidant enzyme that has been shown to protect tissues from reactive oxygen species-induced heparin and heparan sulphate fragmentation, and thus the subsequent neutrophil chemotaxis [ 64 ]. Importantly, heparin and heparan sulphate can antagonize the binding of SARS-CoV-2 to HSPGs and block their cellular internalization [ 93 ]. Through these approaches, OXT has the potential to prevent SARS-CoV-2 entry and disruption of cells.…”

Thein vitroantiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor

“…Heparan sulfate (HS) is a linear and sulfated polysaccharide that is abundantly expressed on the surface of almost all cell types in the forms of HSPGs. The negatively-charged HSPGs often serve as an attachment factor for a diverse of viruses [20,21]; 3) interfere with intracellular trafficking of virus [22]. LF was reported to have antiviral activity against SARS-CoV [17].…”

SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration

“…This study suggests that the heparin-binding site of the spike protein might act as a binding site for Aβ42 peptides and thus could dock to the viral surface and catalyze aggregation of Aβ42. As the receptor binding domain (RBD) of SARS-CoV-2, which is located within the S1 subunit of spike glycoprotein has several heparin binding sites [ [12] , [13] , [14] ], the same mechanism of aggregation of neurodegeneration causing proteins such as Aβ, α-synuclein, tau, prions, and TDP-43 can be observed in COVID-19 infection in the brain.…”