Intracellular Degradation of SARS-CoV-2 N-Protein Caused by Modular Nanotransporters Containing Anti-N-Protein Monobody and a Sequence That Recruits the Keap1 E3 Ligase DOI Creative Commons
Yuri V. Khramtsov, A. V. Ulasov, T. N. Lupanova

и другие.

Pharmaceutics, Год журнала: 2023, Номер 16(1), С. 4 - 4

Опубликована: Дек. 19, 2023

The proper viral assembly relies on both nucleic acids and structural proteins. Thus a biologically active agent that provides the degradation of one these key proteins and/or destroys factory could suppress replication efficiently. nucleocapsid protein (N-protein) is for SARS-CoV-2 virus. As bioactive agent, we offer modular nanotransporter (MNT) developed by us, which, in addition to an antibody mimetic N-protein, contains amino acid sequence attraction Keap1 E3 ubiquitin ligase. This should lead subsequent N-protein. We have shown functional properties modules within MNT permit its internalization into target cells, endosome escape cytosol, binding Using flow cytometry western blotting, demonstrated significant N-protein when A549 A431 cells transfected with plasmid coding were incubated MNTs. proposed MNTs open up new approach treatment diseases.

Язык: Английский

Recent Advances on Targeting Proteases for Antiviral Development DOI Creative Commons
Pedro Henrique Oliveira Borges, Sabrina Baptista Ferreira, Floriano Paes Silva

и другие.

Viruses, Год журнала: 2024, Номер 16(3), С. 366 - 366

Опубликована: Фев. 27, 2024

Viral proteases are an important target for drug development, since they can modulate vital pathways in viral replication, maturation, assembly and cell entry. With the (re)appearance of several new viruses responsible causing diseases humans, like West Nile virus (WNV) recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding mechanisms behind blocking protease’s function is pivotal development antiviral drugs therapeutical strategies. Apart from directly inhibiting protease, usually by targeting its active site, have been explored to impair activity, such as inducing protein aggregation, allosteric sites or degradation cellular proteasomes, which be extremely valuable when considering emerging drug-resistant strains. In this review, we aim discuss advances on a broad range inhibitors, therapies molecular approaches inactivation degradation, giving insight different possible strategies against class target.

Язык: Английский

Процитировано

9
PROTAC unleashed: Unveiling the synthetic approaches and potential therapeutic applications DOI Creative Commons
Narayanaperumal Pravin, Krzysztof Jóźwiak

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 279, С. 116837 - 116837

Опубликована: Сен. 10, 2024

Язык: Английский

Процитировано

4
Lessons learnt from broad-spectrum coronavirus antiviral drug discovery DOI

Andrew A. Bolinger,

Jun Li, Xuping Xie

и другие.

Expert Opinion on Drug Discovery, Год журнала: 2024, Номер 19(9), С. 1023 - 1041

Опубликована: Июль 30, 2024

Introduction Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East (MERS-CoV), and the most recent SARS-CoV-2 responsible for COVID-19 pandemic, pose significant threats to human populations over past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic distress syndromes (ARDS), resulting in high morbidity mortality.

Язык: Английский

Процитировано

1
Structural Investigation of the Interaction Between a GC-376 Based Peptidomimetic PROTAC and the Viral Main Protease of Coxsackievirus B3 to Explore the Applicability of a Broad-Spectrum Antiviral PROTAC DOI Open Access
Alessia De Santis, Deborah Grifagni,

A Orsetti

и другие.

Опубликована: Июль 17, 2024

The conservation of the main protease in viral genomes, combined with absence a homologous humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs minimal host toxicity. GC-376, peptidomimetic 3CL inhibitor, has shown significant efficacy against coronaviruses. Recently, GC-376-based PROTAC was developed to and induce proteosome-mediated degradation dimeric SARS-CoV-2 3CLPro protein. Extending approach, current study investigates application GC-376 3CPro Enteroviruses, specifically characterizing its interaction CVB3 through X-ray crystallography, NMR biophysical techniques. present structural data show that there are some changes between binding 3CLPro, but overall similarity is strong. most notable variation orientation phenylmethyl ester S4 subsite proteases. This linked flexibility protein structure around region catalytic triad by our data. Other variations include distinct ligand interactions subsites S1 S2, influenced presence Glu71 3CPro. Despite these differences, fits well within sites both proteases, demonstrating potential as agent.

Язык: Английский

Процитировано

0
Intracellular Degradation of SARS-CoV-2 N-Protein Caused by Modular Nanotransporters Containing Anti-N-Protein Monobody and a Sequence That Recruits the Keap1 E3 Ligase DOI Creative Commons
Yuri V. Khramtsov, A. V. Ulasov, T. N. Lupanova

и другие.

Pharmaceutics, Год журнала: 2023, Номер 16(1), С. 4 - 4

Опубликована: Дек. 19, 2023

The proper viral assembly relies on both nucleic acids and structural proteins. Thus a biologically active agent that provides the degradation of one these key proteins and/or destroys factory could suppress replication efficiently. nucleocapsid protein (N-protein) is for SARS-CoV-2 virus. As bioactive agent, we offer modular nanotransporter (MNT) developed by us, which, in addition to an antibody mimetic N-protein, contains amino acid sequence attraction Keap1 E3 ubiquitin ligase. This should lead subsequent N-protein. We have shown functional properties modules within MNT permit its internalization into target cells, endosome escape cytosol, binding Using flow cytometry western blotting, demonstrated significant N-protein when A549 A431 cells transfected with plasmid coding were incubated MNTs. proposed MNTs open up new approach treatment diseases.

Язык: Английский

Процитировано

1