ABSTRACT
Heparan sulfate proteoglycans (HSPGs) are cell surface receptors that are involved in the cellular uptake of pathologic 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 nonanticoagulant agents that are capable of antagonizing 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 coronavirus 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.
Subject(s)
Antiviral Agents/metabolism , Betacoronavirus/physiology , Coronavirus Infections/drug therapy , Heparan Sulfate Proteoglycans/metabolism , Peptides/metabolism , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 , Heparan Sulfate Proteoglycans/chemistry , Humans , Pandemics , Peptides/chemistry , Peptides/pharmacology , Peptides/therapeutic use , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistryABSTRACT
Postinfection complications of coronavirus disease 2019 (COVID-19) are still unknown, and one of the long-term concerns in infected people are brain pathologies. The question is that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may be an environmental factor in accelerating the sporadic neurodegeneration in the infected population. In this regard, induction of protein aggregation in the brain by SARS-CoV-2 intact structure or a peptide derived from spike protein subunits needs to be considered in futures studies. In this paper, we discuss these possibilities using pieces of evidence from other viruses.