SARS-CoV-2 inhibitory activity of a short peptide derived from internal fusion peptide of S2 subunit of spike glycoprotein

Stincarelli, Maria Alfreda; Quagliata, Michael; Santo, Andrea Di; Pacini, Lorenzo; Real‐Fernández, Feliciana; Arvia, Rosaria; Rinaldi, Silvia; Papini, Anna Maria; Rovero, Paolo; Giannecchini, Simone

doi:10.1016/j.virusres.2023.199170

Cited by 2 publications

(3 citation statements)

References 44 publications

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Section: Discussionmentioning

confidence: 99%

“…Note that Phe 888 is completely conserved among all human infective CoVs, and that in the subsequent, triggered, postfusion, six-helix bundle conformation, Phe888 is located in the center of the fusion peptide inserted into the target membrane(38). Short peptides designed from the internal fusion peptide region of SARS-CoV-2 S2 have shown high conformation-dependent inhibitory activity against the virus(49).Hence, taken together, this structure, of an open, breathing conformation of the FP may illuminate steps in the fusion cancade and provide a new template for fusion inhibition. A potential role for the open, breathing state in spike function and spike vaccination Although it has not been directly demonstrated whether reversible breathing occurs in wild-type spikes on virions, it is possible that the 'open' S2 may also reflect an intermediate along the pathway to S1 shedding, during the transition from the prefusion conformation to the postfusion conformation.…”

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confidence: 99%

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Structure of a SARS-CoV-2 spike S2 subunit in a pre-fusion, open conformation

Olmedillas,

Rajamanickam,

Avalos

et al. 2023

Preprint

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The 800 million human infections with SARS-CoV-2 and the likely emergence of new variants and additional coronaviruses necessitate a better understanding of the essential spike glycoprotein and the development of immunogens that foster broader and more durable immunity. The S2 fusion subunit is more conserved in sequence, is essential to function, and would be a desirable immunogen to boost broadly reactive antibodies. It is, however, unstable in structure and in its wild-type form, cannot be expressed alone without irreversible collapse into a six-helix bundle. In addition to the irreversible conformational changes of fusion, biophysical measurements indicate that spike also undergoes a reversible breathing action. However, spike in an open, “breathing” conformation has not yet been visualized at high resolution. Here we describe an S2-only antigen, engineered to remain in its relevant, pre-fusion viral surface conformation in the absence of S1. We also describe a panel of natural human antibodies specific for S2 from vaccinated and convalescent individuals. One of these mAbs, from a convalescent individual, afforded a high-resolution cryo-EM structure of the prefusion S2. The structure reveals a complex captured in an “open” conformation with greater stabilizing intermolecular interactions at the base and a repositioned fusion peptide. Together, this work provides an antigen for advancement of next-generation “booster” immunogens and illuminates the likely breathing adjustments of the coronavirus spike.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Structure of a SARS-CoV-2 spike S2 subunit in a pre-fusion, open conformation

Olmedillas,

Rajamanickam,

Avalos

et al. 2023

Preprint

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“…The S2 subunit is anchored to the viral membrane through a transmembrane region. This subunit contains the essential components required for the membrane fusion process, enabling the virus to bind to the cellular membranes and undergo fusion ( Figure 2 A) [ 40 , 41 ].…”

Section: Common Drugs Targeting Coronavirus Entry Into Host Cellsmentioning

confidence: 99%

A Mini-Review on the Common Antiviral Drug Targets of Coronavirus

Wang,

Zhu,

Xing

et al. 2024

Microorganisms

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Coronaviruses in general are a zoonotic pathogen with significant cross-species transmission. They are widely distributed in nature and have recently become a major threat to global public health. Vaccines are the preferred strategy for the prevention of coronaviruses. However, the rapid rate of virus mutation, large number of prevalent strains, and lag in vaccine development contribute to the continuing frequent occurrence of coronavirus diseases. There is an urgent need for new antiviral strategies to address coronavirus infections effectively. Antiviral drugs are important in the prevention and control of viral diseases. Members of the genus coronavirus are highly similar in life-cycle processes such as viral invasion and replication. These, together with the high degree of similarity in the protein sequences and structures of viruses in the same genus, provide common targets for antiviral drug screening of coronaviruses and have led to important advances in recent years. In this review, we summarize the pathogenic mechanisms of coronavirus, common drugs targeting coronavirus entry into host cells, and common drug targets against coronaviruses based on biosynthesis and on viral assembly and release. We also describe the common targets of antiviral drugs against coronaviruses and the progress of antiviral drug research. Our aim is to provide a theoretical basis for the development of antiviral drugs and to accelerate the development and utilization of commonly used antiviral drugs in China.

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SARS-CoV-2 inhibitory activity of a short peptide derived from internal fusion peptide of S2 subunit of spike glycoprotein

Cited by 2 publications

References 44 publications

Structure of a SARS-CoV-2 spike S2 subunit in a pre-fusion, open conformation

Structure of a SARS-CoV-2 spike S2 subunit in a pre-fusion, open conformation

A Mini-Review on the Common Antiviral Drug Targets of Coronavirus

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