Peptide-Based Strategies Against SARS-CoV-2 Attack: An Updated In Silico Perspective

Abstract

Because of its scale and suddenness, the SARS-CoV-2 pandemic has created an unprecedented challenge in terms of drug development. Apart from being natural candidates for vaccine design, peptides are a class of compounds well suited to target protein-protein interactions, and peptide drug development benefits from the progress of in silico protocols that have emerged within the last decade. Here, we review the different strategies that have been considered for the development of peptide drugs against SARS-CoV-2. Thanks to progress in experimental structure determination, structural information has rapidly become available for most of the proteins encoded by the virus, easing in silico analyses to develop drugs or vaccines. The repurposing of antiviral/antibacterial peptide drugs has not been successful so far. The most promising results, but not the only ones, have been obtained targeting the interaction between SARS-CoV-2 spike protein and the Angiotensin-Converting Enzyme 2, which triggers cellular infection by the virus and its replication. Within months, structure-based peptide design has identified competing for picomolar candidates for the interaction, proving that the development of peptide drugs targeting protein-protein interactions is maturing. Although no drug specifically designed against SARS-CoV-2 has yet reached the market, lessons from peptide drug development against SARS-CoV-2 suggest that peptide development is now a plausible alternative to small compounds.

Computational design of anti-cancer peptides tailored to target specific tumor markers

“…The strong binding affinity of these peptides with these receptors suggests their potential to inhibit apoptosis while simultaneously inhibiting angiogenesis through their neutralizing effect on DARC. This dual action may effectively impede both apoptosis and angiogenesis [ 46 , 54 ].…”

“…Osteoprotegerin (OPG) plays a key role in regulating bone metastasis, controlling tumor invasion within bone tissue, and modulating cellular integrity [ 54 ]. The OPG/RANKL/RANK pathway holds a pivotal role in bone homeostasis and represents a therapeutic target for various bone diseases, including osteoporosis [ 55 , 56 ].…”

Főbb trendek a szintetikus peptidekkel folytatott kutatási témákban • Main Trends in Research Topics with Synthetic Peptides

“…A kutásokat a SARS-CoV-2-vírus okozta világjárvány példátlan mértékben felgyorsította. A SARS-CoV-2 elleni peptid gyógyszerek fejlesztése során a szerkezeti információk gyorsan elérhetővé váltak (elsősorban a vírus által kódolt fehérjék tekintetében), megkönnyítve az in silico elemzéseket, így elősegítve a peptidalapú gyógyszerfejlesztés lehetőségeit is (Moroy-Tuffery, 2022).…”

Dissection of Antibody Responses of Gam-COVID-Vac-Vaccinated Subjects Suggests Involvement of Epitopes Outside RBD in SARS-CoV-2 Neutralization

“…The identification of epitopes recognized by antibodies from vaccinated subjects involved in virus neutralization is crucial not only for understanding the mechanism of the action of existing vaccines but also for the development of refined active vaccination and passive immunization strategies against COVID-19 [ 11 , 12 ]. Most of the current vaccines are focused on obtaining an S-specific antibody response with special attention to RBD-specific antibody response, because it has been seen that RBD-specific antibodies are correlated with high neutralizing activity against SARS-CoV-2 [ 13 , 14 , 15 ].…”