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

Stilbenes: Source plants, chemistry, biosynthesis, pharmacology, application and problems related to their clinical Application-A comprehensive review DOI

Tekleab Teka,

Lele Zhang,

Xiaoyan Ge

et al.

Phytochemistry, Journal Year: 2022, Volume and Issue: 197, P. 113128 - 113128

Published: Feb. 17, 2022

Language: Английский

Citations

120
E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway DOI Creative Commons
Elaine Luiza Santos Soares de Mendonça, Jadriane de Almeida Xavier, Marilene Brandão Tenório Fragoso

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 232 - 232

Published: Feb. 9, 2024

Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative (in microorganism cultures). The latter is metabolic engineering strategy to enhance production due stilbenes recognized pharmacological medicinal potential. It believed that in the human body, these potential activities be modulated by regulation of nuclear factor erythroid derived 2 (Nrf2), which increases expression antioxidant enzymes. Given this, our review aims critically analyze evidence regarding E-stilbenes metabolism Nrf2 activation pathway, with emphasis on inflammatory oxidative stress aspects related pathophysiology chronic diseases. In this comprehensive literature review, it observed despite broad number stilbenes, those most frequently explored clinical trials preclinical studies vitro vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, pinosylvin. some cases, depending dose/concentration chemical nature stilbene, was possible identify pathway. Furthermore, use experimental models presented challenge comparing results. view above, suggested have relationship whether directly indirectly, different biological pathways, diseases conditions mainly inflammation stress.

Language: Английский

Citations

40
Natural Products, Alone or in Combination with FDA-Approved Drugs, to Treat COVID-19 and Lung Cancer DOI Creative Commons
Liyan Yang, Zhonglei Wang

Biomedicines, Journal Year: 2021, Volume and Issue: 9(6), P. 689 - 689

Published: June 18, 2021

As a public health emergency of international concern, the highly contagious coronavirus disease 2019 (COVID-19) pandemic has been identified as severe threat to lives billions individuals. Lung cancer, malignant tumor with highest mortality rate, brought significant challenges both human and economic development. Natural products may play pivotal role in treating lung diseases. We reviewed published studies relating natural products, used alone or combination US Food Drug Administration-approved drugs, active against acute respiratory syndrome 2 (SARS-CoV-2) cancer from 1 January 2020 31 May 2021. A wide range can be considered promising anti-COVID-19 anti-lung agents have gained widespread attention, including monotherapy for treatment SARS-CoV-2 (ginkgolic acid, shiraiachrome A, resveratrol, baicalein) (daurisoline, graveospene deguelin, erianin) FDA-approved anti-SARS-CoV-2 (cepharanthine plus nelfinavir, linoleic acid remdesivir) (curcumin cisplatin, celastrol gefitinib). demonstrated potential value assistance nanotechnology, drug therapies, codrug strategy, this “natural remedy” could serve starting point further development these

Language: Английский

Citations

91
Schaftoside inhibits 3CLpro and PLpro of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19 DOI Creative Commons
Yi Yang, Meng Zhang,

Heng Xue

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(11), P. 4154 - 4164

Published: Aug. 9, 2022

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like (PLpro) are key targets discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro PLpro with IC50 values of 1.73 ± 0.22 3.91 0.19 μmol/L, respectively, virus in Vero E6 cells EC50 11.83 3.23 μmol/L. Hydrogen–deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together site-directed mutagenesis indicated antiviral activities were related non-covalent interactions H41, G143 R188 3CLpro, K157, E167 A246 PLpro. Moreover, proteomics analysis cytokine assay revealed also regulated immune response inflammation host cells. anti-inflammatory confirmed on lipopolysaccharide-induced lung injury mice. Schaftoside showed good safety pharmacokinetic property, could be promising drug candidate for prevention treatment COVID-19.

Language: Английский

Citations

59
ChatGPT in Drug Discovery DOI Creative Commons
Gaurav Sharma, Abhishek Thakur

Published: Jan. 31, 2023

ChatGPT is a language model developed by OpenAI. It machine learning that has been trained on large dataset of human language, allowing it to generate human-like text. can be used for variety natural processing tasks such as translation, text summarization, and question answering. In the current work we have discussed application in drug discovery.

Language: Английский

Citations

44
Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach DOI Creative Commons
Kumaravel Kaliaperumal, Limbadri Salendra, Yonghong Liu

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 2, 2023

Introduction Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of discovery medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, fauna tend to produce interesting types importance anticancer, antiviral, anti-tuberculosis properties. Methods An organic ethyl acetate extract Penicillium verruculosum sponge-derived Spongia officinalis yielded seven different which purified through HPLC. The isolated compounds averufin (1), aspergilol-A (2), sulochrin (3), monomethyl (4), methyl emodin (5), citreorosein (6), diorcinol (7). All were characterized by high-resolution NMR spectral studies. compounds', such as antimicrobial, anti-tuberculosis, subjected bioactivity screening. Results Out tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have IC 50 concentration 1.00μm, nearly significant that standard taxol. A virtual computational molecular docking approach antigens revealed binds strongly protein target alpha, beta-tubulin (1JFF), a −10.98 binding score. Consecutive OSIRIS Lipinski ADME pharmacokinetic validation has good properties score, solubility, mutagenic nature. Furthermore, (2) first report on strain. Discussion We concluded can be taken further preliminary clinical trials like animal model in-vivo studies pharmacodynamic future prospect screening validated present experimental findings.

Language: Английский

Citations

34
SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells DOI Creative Commons
Kai Yang, Shiyun Liu, Yan Han

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 14, 2023

Abstract Exposure to the spike protein or receptor-binding domain (S-RBD) of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy. In this study, angiotensin-converting enzyme 2 humanized inbred (hACE2 Tg) mice cultured were used investigate how protein/S-RBD impacts endothelium. Results show that S-RBD leads acute-to-prolonged induction intracellular free calcium concentration ([Ca 2+ ] i ) via acute activation TRPV4, prolonged upregulation mechanosensitive channel Piezo1 store-operated (SOCC) key component Orai1 in human arterial (PAECs). mechanism, interacts with ACE2 induce formation clusters involving Orai1, TRPC1, facilitate SOCC, lead elevated apoptosis. These effects are blocked by Kobophenol A, which inhibits binding between ACE2, chelator, BAPTA-AM. Blockade SOCC GsMTx4 effectively protects S-RBD-induced microvascular damage hACE2 Tg normalizing [Ca . Comparing prototypic strain, Omicron variants (BA.5.2 XBB) less severe cell Transcriptomic analysis indicates confers more than Delta Lambda S-RBD. summary, study provides compelling evidence could persistent triggering through Orai1. Targeted inhibition ACE2-Piezo1/SOCC-[Ca axis proves a powerful strategy treat diseases.

Language: Английский

Citations

30
Discovery of novel PDGFR inhibitors targeting non-small cell lung cancer using a multistep machine learning assisted hybrid virtual screening approach DOI Creative Commons

Sandhi Kranthi Reddy,

S. V. G. Reddy, Syed Hussain Basha

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(2), P. 851 - 869

Published: Jan. 1, 2025

Identified novel PDGFR inhibitor targeting non-small cell lung cancer using machine learning from vast library of 1.04 million compounds.

Language: Английский

Citations

2
The Natural Stilbenoid (–)-Hopeaphenol Inhibits Cellular Entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7, and B.1.351 Variants DOI Creative Commons
Ian Tietjen, Joel Cassel,

Emery T. Register

et al.

Antimicrobial Agents and Chemotherapy, Journal Year: 2021, Volume and Issue: 65(12)

Published: Sept. 20, 2021

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding viral spike receptor domain (RBD) host angiotensin-converting enzyme II (ACE2) may be effective inhibitors cell entry. Here, we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 assay identified (-)-hopeaphenol, resveratrol tetramer, in addition vatalbinoside A vaticanol B, as potent selective For example, (-)-hopeaphenol disrupted 50% inhibitory concentration (IC50) 0.11 μM, contrast an IC50 28.3 μM against unrelated ligand/receptor pair PD-1/PD-L1 (selectivity index, 257.3). When assessed USA-WA1/2020 variant, also inhibited entry VSVΔG-GFP reporter pseudovirus expressing into ACE2-expressing Vero-E6 cells vitro replication infectious virus cytopathic effect yield reduction assays (50% concentrations [EC50s], 10.2 23.4 μM) without cytotoxicity approaching activities control antiviral remdesivir (EC50s, 1.0 7.3 μM). Notably, two concern, B.1.1.7/Alpha B.1.351/Beta both spike-containing similar or improved over variant. These results identify related stilbenoid analogues across multiple

Language: Английский

Citations

42
Natural products as potential lead compounds to develop new antiviral drugs over the past decade DOI

Jing-Han Zhao,

Yuewei Wang, Jin Yang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 260, P. 115726 - 115726

Published: Aug. 15, 2023

Language: Английский

Citations

20