Mpox (formerly monkeypox): pathogenesis, prevention and treatment

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

Published: Dec. 27, 2023

In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America rapidly spread to more than 100 regions. The World Health Organization declared the be public health emergency international concern due rapid virus. Consequently, nations intensified their efforts explore treatment strategies aimed at combating infection its dissemination. Nevertheless, available therapeutic options for virus remain limited. So far, only few numbers antiviral compounds have been approved by regulatory authorities. Given high mutability virus, certain mutant strains shown resistance existing pharmaceutical interventions. This highlights urgent need develop novel drugs that can combat both drug potential threat bioterrorism. Currently, there is lack comprehensive literature on pathophysiology Mpox. To address this issue, we conducted review covering physiological pathological processes infection, summarizing latest progress anti-Mpox drugs. Our analysis encompasses currently employed clinical settings, as well newly identified small-molecule antibody displaying efficacy against Furthermore, gained valuable insights from process development, including repurposing drugs, discovery targets driven artificial intelligence, preclinical development. purpose provide readers with overview current knowledge

Language: Английский

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Phenylboronic Acid-Modified Membrane-Like Magnetic Quantum Dots Enable the Ultrasensitive and Broad-Spectrum Detection of Viruses by Lateral Flow Immunoassay

ACS Nano, Journal Year: 2024, Volume and Issue: 18(26), P. 16752 - 16765

Published: June 20, 2024

Although lateral flow immunochromatographic assay (LFIA) is an effective point-of-care testing technology, it still cannot achieve broad-spectrum and ultrasensitive detection of viruses. Herein, we propose a multiplex LFIA platform using two-dimensional graphene oxide (GO)-based magnetic fluorescent nanofilm (GF@DQD) as multifunctional probe 4-aminophenylboronic acid (APBA) recognition molecule for viral glycoprotein detection. GF@DQD-APBA with enhanced magnetic/fluorescence properties universal capture ability multiple viruses was easily prepared through the electrostatic adsorption one layer density-controlled Fe3O4 nanoparticles (NPs) thousands small CdSe/ZnS-MPA quantum dots (QDs) on monolayer GO sheet followed by chemical coupling APBA QD surface. The enabled specific determination different target test strip arbitrary combination antibody-modified strip, thus greatly improving efficiency reducing cost difficulty proposed technique can simultaneously sensitively diagnose three newly emerged within 20 min limits down to pg/mL level. excellent practicability GF@DQD-APBA-LFIA also demonstrated in 34 clinical specimens positive SARS-CoV-2, revealing its potential epidemic control on-site

Language: Английский

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Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review

Antibiotics, Journal Year: 2023, Volume and Issue: 12(7), P. 1220 - 1220

Published: July 22, 2023

Bacterial infections have attracted the attention of researchers in recent decades, especially due to special problems they faced, such as their increasing diversity and resistance antibiotic treatment. The emergence development SARS-CoV-2 infection stimulated even more research find new structures with antimicrobial antiviral properties. Among heterocyclic compounds remarkable therapeutic properties, benzimidazoles, triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, literature last decade reports benzimidazole-triazole hybrids improved biological properties compared simple mono-heterocyclic compounds. This review aims provide an update on synthesis methods these hybrids, along activities, well structure-activity relationship reported literature. It was found that presence certain groups grafted onto benzimidazole and/or triazole nuclei (-F, -Cl, -Br, -CF3, -NO2, -CN, -CHO, -OH, OCH3, COOCH3), some heterocycles (pyridine, pyrimidine, thiazole, indole, isoxazole, thiadiazole, coumarin) increases activity hybrids. Also, oxygen sulfur atom bridge connecting rings generally mentions only benzimidazole-1,2,3-triazole Both for additional ring activity, which is agreement three-dimensional binding mode summarizes advances derivatives potential agents covering articles published from 2000 2023.

Language: Английский

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Purine but Not Pyrimidine De Novo Nucleotide Biosynthesis Inhibitors Strongly Enhance the Antiviral Effect of Corresponding Nucleobases Against Dengue Virus

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 210 - 210

Published: Jan. 7, 2025

Every year, dengue virus affects hundreds of millions individuals worldwide. To date, there is no specific medication to treat infections. Nucleobases, the base a nucleoside without ribose, are understudied as potential treatments for viral Antiviral nucleobases converted in infected cells their corresponding triphosphate active form. Importantly, conversion nucleotide form and antiviral effect can be enhanced when combined with de novo biosynthesis inhibitors. In this work, we evaluated seven purine pyrimidine alone or six inhibitors, including novel prodrugs. Our study revealed that while strong potentiation by inhibitors was observed, were not potentiated possibly highlighting significant difference between modulation versus pathways impact on nucleobase potentiation. Most effects observed Favipiravir, T-1105, ribavirin synthesis These results because drug combinations may solve limited efficacy some drugs such Favipiravir.

Language: Английский

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DHODH inhibitors: What will it take to get them into the clinic as antivirals?

Antiviral Research, Journal Year: 2025, Volume and Issue: 236, P. 106099 - 106099

Published: Feb. 10, 2025

The emergence of new human viruses with epidemic or pandemic potential has reaffirmed the urgency to develop effective broad-spectrum antivirals (BSAs) as part a strategic framework for prevention and preparedness. To this end, host nucleotide metabolic pathway been subject intense investigation in search host-targeting agents (HTAs) BSA activity. In particular, dihydroorotate dehydrogenase (hDHODH), rate-limiting enzyme de novo pyrimidine biosynthetic pathway, identified preferential target HTAs. Viral replication fact relies on cellular replenishment, making hDHODH an ideal HTA target. depletion pool that ensues pharmacological inhibition activity elicits through three distinct mechanisms: it blocks viral DNA RNA synthesis; activates effector mechanisms innate antiviral response; mitigates virus-induced inflammatory response. However, despite spectacular results obtained vitro, inhibitors examined mono-drug therapies animal models infections clinical trials have produced disappointing levels overall efficacy. overcome inherent limitation, strategies based multi-drug combination treatments should be considered enable efficacy hDHODH-targeted therapies. Here, we review state-of-the-art applications inhibitors, discuss challenges emerged from their testing consider how they might addressed advance development treatment diseases.

Language: Английский

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Design of quinoline SARS-CoV-2 papain-like protease inhibitors as oral antiviral drug candidates

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 13, 2025

The ever-evolving SARS-CoV-2 variants necessitate the development of additional oral antivirals. This study presents systematic design quinoline-containing papain-like protease (PLpro) inhibitors as potential antiviral drug candidates. By leveraging recently discovered Val70Ub binding site in PLpro, we designed a series quinoline analogs demonstrating potent PLpro inhibition and activity. Notably, X-ray crystal structures 6 lead compounds reveal that 2-aryl substitution can occupy either expected or BL2 groove flipped orientation. vivo Jun13296 exhibits favorable pharmacokinetic properties against nirmatrelvir-resistant mutants. In mouse model infection, treatment with significantly improves survival, reduces body weight loss lung viral titers, prevents tissue damage. These results underscore promising candidates, instilling hope for future treatment. inhibitor, Jun13296, displays efficacy infection inhibits mutants, rendering it candidate.

Language: Английский

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Small Molecule Drugs Targeting Viral Polymerases

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 661 - 661

Published: May 20, 2024

Small molecules that specifically target viral polymerases—crucial enzymes governing genome transcription and replication—play a pivotal role in combating infections. Presently, approved polymerase inhibitors cover nine human viruses, spanning both DNA RNA viruses. This review provides comprehensive analysis of these licensed drugs, encompassing nucleoside/nucleotide (NIs), non-nucleoside (NNIs), mutagenic agents. For each compound, we describe the specific targeted virus related enzyme, mechanism action, relevant bioactivity data. wealth information serves as valuable resource for researchers actively engaged antiviral drug discovery efforts, offering complete overview established strategies well insights shaping development next-generation therapeutics.

Language: Английский

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Paving new roads toward the advancement of broad‐spectrum antiviral agents

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(1)

Published: Jan. 1, 2024

Abstract Broad‐spectrum antivirals (BSAs) have the advantageous property of being effective against a wide range viruses with single drug, offering promising therapeutic solution for largely unmet need in treating both existing and emerging viral infections. In this review, we summarize current strategies development novel BSAs, focusing on either targeting commonalities during replication multiple or systemic immunity humans. comparison to BSAs that target replication, these immuno‐modulatory agents possess an expanded spectrum antiviral activity. However, is double‐edged sword, maintaining immune homeostasis ultimately dictates health status hosts Therefore, establishing ideal goal immuno‐modulation interventions crucial. Herein propose bionic approach inspired by mimicking bats, which more robust system combating invasions, compared addition, discuss empirical treat diverse infections using traditional Chinese medicines (TCMs), mainly through bidirectional restore disrupted homeostasis. Advancing our understanding bats mechanisms underlying TCMs will significantly contribute future BSAs.

Language: Английский

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Host-targeted antivirals against SARS-CoV-2 in clinical development - prospect or disappointment?

Antiviral Research, Journal Year: 2025, Volume and Issue: 235, P. 106101 - 106101

Published: Feb. 7, 2025

The global response to the COVID-19 pandemic, caused by novel SARS-CoV-2 virus, has seen an unprecedented increase in development of antiviral therapies. Traditional strategies have primarily focused on direct-acting antivirals (DAAs), which specifically target viral components. In recent years, increasing attention was given alternative approach aiming exploit host cellular pathways or immune responses inhibit replication, led so-called host-targeted (HTAs). emergence and promoted a boost this field. Numerous HTAs been tested demonstrated their potential against through vitro vivo studies. However, striking contrast, only limited number successfully progressed advanced clinical trial phases (2-4), even less entered practice. This review aims explore current landscape targeting that reached phase 2-4 trials. Additionally, it will challenges faced gaining regulatory approval market availability.

Language: Английский

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Isolation and structure elucidation of Dm-CVNH, a new cyanovirin-N homolog with activity against SARS-CoV-2 and HIV-1

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108319 - 108319

Published: Feb. 1, 2025

An anti-HIV screening of natural product extracts resulted in the discovery a new antiviral protein through bioassay-guided fractionation an aqueous extract ascidian Didemnum molle. The was sequenced combination tandem mass spectroscopy and N-terminal Edman degradation peptide fragments after series endoproteinase digestions. primary amino acid sequence disulfide bonding pattern 102-amino were closely related to cyanovirin-N (CV-N). This CV-N homolog named Dm-CVNH. Alphafold2 prediction tertiary structure, highly similar CV-N, comprised two symmetrically domains that contained five β-strands α-helical turns each. Dm-CVNH showed specificity for high mannose oligomannose structures, bound HIV-1 gp-120 potently inactivated HIV neutralization assays (EC50 0.95 nM). inhibited infection SARS-CoV-2 live virus = 11-18 nM) shown bind S1 domain Spike glycoprotein. behaved manner binding with 2:1 stoichiometry (both WH-1 Omicron variants) preferring variant (Kd 42 original 89 Spike. sensitivity emergent strains mirrored viral where XBB.1.16 JN.1 (IC50

Language: Английский

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