Cleavage of the Glycoprotein of Arenaviruses

Pasquato, Antonella; Cendron, Laura; Kunz, Stefan

doi:10.1007/978-3-319-75474-1_3

Cited by 8 publications

(8 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The smaller S segment codes for the glycoprotein precursor (GPC) and nucleoprotein (NP), which binds the viral RNA within the capsid ( Figure 2 ). The GPC is cleaved post-translationally into the stable signal peptide (SSP), GP1 and GP2 ( Beyer et al, 2003 ; Rojek et al, 2008 ; Burri et al, 2012 ; Pasquato et al, 2018 ). Together, these form a trimer on the viral membrane; arenaviruses are unique in retaining the SSP as part of the GP complex ( Burri et al, 2012 ; Pasquato et al, 2018 ).…”

Section: Arenavirus Classification Structure and Replicationmentioning

confidence: 99%

Entry inhibitors as arenavirus antivirals

Iyer,

Yan,

Ross

2024

Front. Microbiol.

View full text Add to dashboard Cite

Arenaviruses belonging to the Arenaviridae family, genus mammarenavirus, are enveloped, single-stranded RNA viruses primarily found in rodent species, that cause severe hemorrhagic fever in humans. With high mortality rates and limited treatment options, the search for effective antivirals is imperative. Current treatments, notably ribavirin and other nucleoside inhibitors, are only partially effective and have significant side effects. The high lethality and lack of treatment, coupled with the absence of vaccines for all but Junín virus, has led to the classification of these viruses as Category A pathogens by the Centers for Disease Control (CDC). This review focuses on entry inhibitors as potential therapeutics against mammarenaviruses, which include both New World and Old World arenaviruses. Various entry inhibition strategies, including small molecule inhibitors and neutralizing antibodies, have been explored through high throughput screening, genome-wide studies, and drug repurposing. Notable progress has been made in identifying molecules that target receptor binding, internalization, or fusion steps. Despite promising preclinical results, the translation of entry inhibitors to approved human therapeutics has faced challenges. Many have only been tested in in vitro or animal models, and a number of candidates showed efficacy only against specific arenaviruses, limiting their broader applicability. The widespread existence of arenaviruses in various rodent species and their potential for their zoonotic transmission also underscores the need for rapid development and deployment of successful pan-arenavirus therapeutics. The diverse pool of candidate molecules in the pipeline provides hope for the eventual discovery of a broadly effective arenavirus antiviral.

show abstract

Section: Arenavirus Classification Structure and Replicationmentioning

confidence: 99%

Entry inhibitors as arenavirus antivirals

Iyer,

Yan,

Ross

2024

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Unlike other bunyaviruses, the arenavirus glycoprotein precursor contains only a single stable SP (SSP), which is located at the N-terminus ( Figure 3 E). During glycoprotein maturation, the SSP is cleaved from the precursor by a cellular SPase, and GP1 is separated from GP2 by subtilase SK1/S1P [ 52 , 72 , 73 , 74 , 75 ]. Unique to arenaviruses, the SSP remains stable upon cleavage by cellular SPase in the ER and associates with GP1/GP2 heterodimers to form an SSP/GP1/GP2 complex [ 76 , 77 ].…”

Section: Processing Of Bunyavirus Glycoprotein Precursorsmentioning

confidence: 99%

Recent Advances in Bunyavirus Glycoprotein Research: Precursor Processing, Receptor Binding and Structure

Hulswit

Paesen

Bowden

et al. 2021

Viruses

View full text Add to dashboard Cite

The Bunyavirales order accommodates related viruses (bunyaviruses) with segmented, linear, single-stranded, negative- or ambi-sense RNA genomes. Their glycoproteins form capsomeric projections or spikes on the virion surface and play a crucial role in virus entry, assembly, morphogenesis. Bunyavirus glycoproteins are encoded by a single RNA segment as a polyprotein precursor that is co- and post-translationally cleaved by host cell enzymes to yield two mature glycoproteins, Gn and Gc (or GP1 and GP2 in arenaviruses). These glycoproteins undergo extensive N-linked glycosylation and despite their cleavage, remain associated to the virion to form an integral transmembrane glycoprotein complex. This review summarizes recent advances in our understanding of the molecular biology of bunyavirus glycoproteins, including their processing, structure, and known interactions with host factors that facilitate cell entry.

show abstract

“…In turn, this would provide the patient’s immune system a window of opportunity to develop an appropriate antiviral immune response to clear the virus off. Unfortunately, the only small inhibitor available PF-429242 failed to reach clinical applications due to its poor pharmacokinetic properties [ 137 ], thus begging for a potent and safe SKI-1/S1P inhibitor as an antiviral to fight such deadly infections [ 132 , 155 , 156 , 157 ].…”

Section: Proprotein Convertases and Enveloped Virusesmentioning

confidence: 99%

How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?

Seidah

Pasquato

Andréo

2021

Viruses

Self Cite

View full text Add to dashboard Cite

Inhibition of the binding of enveloped viruses surface glycoproteins to host cell receptor(s) is a major target of vaccines and constitutes an efficient strategy to block viral entry and infection of various host cells and tissues. Cellular entry usually requires the fusion of the viral envelope with host plasma membranes. Such entry mechanism is often preceded by “priming” and/or “activation” steps requiring limited proteolysis of the viral surface glycoprotein to expose a fusogenic domain for efficient membrane juxtapositions. The 9-membered family of Proprotein Convertases related to Subtilisin/Kexin (PCSK) serine proteases (PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1/S1P, and PCSK9) participate in post-translational cleavages and/or regulation of multiple secretory proteins. The type-I membrane-bound Furin and SKI-1/S1P are the major convertases responsible for the processing of surface glycoproteins of enveloped viruses. Stefan Kunz has considerably contributed to define the role of SKI-1/S1P in the activation of arenaviruses causing hemorrhagic fever. Furin was recently implicated in the activation of the spike S-protein of SARS-CoV-2 and Furin-inhibitors are being tested as antivirals in COVID-19. Other members of the PCSK-family are also implicated in some viral infections, such as PCSK9 in Dengue. Herein, we summarize the various functions of the PCSKs and present arguments whereby their inhibition could represent a powerful arsenal to limit viral infections causing the present and future pandemics.

show abstract

Cleavage of the Glycoprotein of Arenaviruses

Cited by 8 publications

References 124 publications

Entry inhibitors as arenavirus antivirals

Entry inhibitors as arenavirus antivirals

Recent Advances in Bunyavirus Glycoprotein Research: Precursor Processing, Receptor Binding and Structure

How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?

Contact Info

Product

Resources

About