The Main Protease of SARS-CoV-2 as a Target for Phytochemicals against Coronavirus DOI Creative Commons
Shaza S. Issa, С. В. Сокорнова, Roman R. Zhidkin

et al.

Plants, Journal Year: 2022, Volume and Issue: 11(14), P. 1862 - 1862

Published: July 17, 2022

In late December 2019, the first cases of COVID-19 emerged as an outbreak in Wuhan, China that later spread vastly around world, evolving into a pandemic and one worst global health crises modern history. The causative agent was identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although several vaccines were authorized for emergency use, constantly emerging new viral mutants limited treatment options drastically highlighted need developing efficient this disease. One most important components to target purpose is main protease (Mpro). This enzyme excellent potential drug, it essential replication has no closely related homologues humans, making its inhibitors unlikely be toxic. Our review describes variety approaches could applied search among plant-derived compounds, including virtual silico screening (a data-driven approach), which structure-based or fragment-guided, classical approach high-throughput screening, antiviral activity cell-based assays. We will focus on classes compounds reported Mpro, phenols polyphenols, alkaloids, terpenoids.

Language: Английский

Emerging Landscape of Nanobodies and Their Neutralizing Applications against SARS-CoV-2 Virus DOI Open Access

Xuemei Feng,

Hu Wang

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: 6(7), P. 925 - 942

Published: June 5, 2023

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease 2019 (COVID-19) has significantly altered people's way of life. Despite widespread knowledge vaccination, mask use, and avoidance close contact, COVID-19 is still spreading around world. Numerous research teams are examining SARS-CoV-2 infection process to discover strategies identify, prevent, treat limit spread this chronic illness restore lives normalcy. Nanobodies have advantages over polyclonal monoclonal antibodies (Ab) Ab fragments, including reduced size, high stability, simplicity in manufacture, compatibility with genetic engineering methods, lack solubility aggregation issues. Recent studies shown nanobodies target receptor-binding domain disrupt ACE2 interactions helpful prevention treatment SARS-CoV-2-infected animal models, despite evidence human patients. creation evaluation nanobodies, as well their diagnostic therapeutic applications against COVID-19, discussed paper.

Language: Английский

Citations

10
Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2 DOI Creative Commons

Larysa V. Yevsieieva,

Kateryna Lohachova, Alexander Kyrychenko

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(50), P. 35500 - 35524

Published: Jan. 1, 2023

The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in world healthcare system. Despite some progress creation of antiviral vaccines and mass vaccination population, number patients continues grow because spread new mutations. There is an urgent need for direct-acting drugs capable suppressing or stopping main mechanisms reproduction SARS-CoV-2. Several studies have shown that successful replication virus cell requires proteolytic cleavage protein structures virus. Two proteases are crucial replicating other coronaviruses: protease (Mpro) papain-like (PLpro). In this review, we summarize essential viral proteins required its life cycle as targets chemotherapy infection provide critical summary development against COVID-19 from drug repurposing strategy up molecular design novel covalent non-covalent agents inhibiting replication. We overview choice Mpro PLpro promising pharmacological impact on cycle.

Language: Английский

Citations

10
Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation DOI Creative Commons
João Augusto Pereira da Rocha, Renato Araújo da Costa,

Andréia do Socorro Silva da Costa

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 22, 2024

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease SARS-CoV-2, Mpro, a key enzyme that plays vital role in mediating viral replication and transcription. In this study, comprehensive computational approach was employed to investigate binding affinity, selectivity, stability natural product candidates as potential new antivirals acting on polyprotein processing mediated by Mpro. A library 288 flavonoids extracted from Brazilian biodiversity screened select Mpro inhibitors. An initial filter based Lipinski's rule five applied, 204 compounds did not violate any Lipinski rules were selected. then docked into active site using GOLD program, poses subsequently re-scored MM-GBSA (Molecular Mechanics Generalized Born Surface Area) free energy calculations performed AmberTools23. top with best values selected analysis their interactions residues protein. Next, we conducted toxicity drug-likeness analysis, non-toxic subjected molecular dynamics simulation calculation MM-PBSA Poisson-Boltzmann method. It observed had lower than co-crystal ligand. Furthermore, these also formed hydrogen bonds two important residues, Cys145 Glu166, Two passed showed stable conformations during simulations. Among these, NuBBE_867 exhibited value compared crystallographic inhibitor. Therefore, study suggests could be inhibitor against may further examined confirm our results.

Language: Английский

Citations

3
3C-like proteases in SARS-CoV-2 DOI Open Access
Kenana Al Adem, Juliana C. Ferreira,

Adrian J. Villanueva

et al.

Bioscience Reports, Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Coronaviruses constitute a significant threat to the human population. Severe acute respiratory syndrome coronavirus-2, SARS-CoV-2, is highly pathogenic coronavirus that has caused COVID-19 pandemic. It led global viral outbreak with an exceptional spread and high death toll, highlighting need for effective antiviral strategies. 3-chymotrypsin-like protease (3CLpro), main in plays indispensable role SARS-CoV-2 life cycle by cleaving polyprotein produce eleven individual non-structural proteins necessary replication. 3CLpro one of two proteases function new particles. conserved cysteine identical structural folds all known coronaviruses. Inhibitors binding affinity will prevent cleavage polyproteins, thus impeding Multiple strategies have been implemented screen inhibitors against 3CLpro, including peptide-like small molecule covalently non-covalently bind active site, respectively. In addition, allosteric sites identified molecules could make non-competitive 3CLpro. essence, this review serves as comprehensive guide understanding intricacies functional dynamics emphasizing key findings elucidate its SARS-CoV-2. Notably, critical resource recognizing advancements identifying developing COVID-19, some which are already approved clinical use patients.

Language: Английский

Citations

3
The Main Protease of SARS-CoV-2 as a Target for Phytochemicals against Coronavirus DOI Creative Commons
Shaza S. Issa, С. В. Сокорнова, Roman R. Zhidkin

et al.

Plants, Journal Year: 2022, Volume and Issue: 11(14), P. 1862 - 1862

Published: July 17, 2022

In late December 2019, the first cases of COVID-19 emerged as an outbreak in Wuhan, China that later spread vastly around world, evolving into a pandemic and one worst global health crises modern history. The causative agent was identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although several vaccines were authorized for emergency use, constantly emerging new viral mutants limited treatment options drastically highlighted need developing efficient this disease. One most important components to target purpose is main protease (Mpro). This enzyme excellent potential drug, it essential replication has no closely related homologues humans, making its inhibitors unlikely be toxic. Our review describes variety approaches could applied search among plant-derived compounds, including virtual silico screening (a data-driven approach), which structure-based or fragment-guided, classical approach high-throughput screening, antiviral activity cell-based assays. We will focus on classes compounds reported Mpro, phenols polyphenols, alkaloids, terpenoids.

Language: Английский

Citations

15