Small molecules in the treatment of COVID-19

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 5, 2022

Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies economies. Until now, effective therapeutics against are in high demand. Along with our improved understanding the structure, function, pathogenic process SARS-CoV-2, many small molecules potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition viral proteins such as RdRp M pro , interference host enzymes including ACE2 proteases, blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, NLRP3 pathways, regarded feasible drug development. development treat achieved strategies, computer-aided lead compound design screening, natural product discovery, repurposing, combination therapy. Several representative remdesivir paxlovid proved or authorized emergency use countries. And candidates entered clinical-trial stage. Nevertheless, due epidemiological features variability issues it is necessary continue exploring novel COVID-19. This review discusses current findings for treatment. Moreover, their detailed mechanism action, chemical structures, preclinical clinical efficacies discussed.

Language: Английский

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Synergism between remdesivir and ribavirin leads to SARS‐CoV‐2 extinction in cell culture

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(15), P. 2636 - 2654

Published: April 14, 2024

There is a need for effective anti-COVID-19 treatments, mainly individuals at risk of severe disease such as the elderly and immunosuppressed. Drug repositioning has proved in identifying drugs that can find new application control coronavirus disease, particular COVID-19. The purpose present study was to synergistic antiviral combinations COVID-19 based on lethal mutagenesis.

Language: Английский

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Potential Therapeutics and Vaccines: Current progress and challenges in developing antiviral treatments or vaccines for Oropouche Virus

Diagnostic Microbiology and Infectious Disease, Journal Year: 2025, Volume and Issue: 111(3), P. 116699 - 116699

Published: Jan. 20, 2025

Language: Английский

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Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(8), P. 6851 - 6879

Published: Aug. 17, 2023

The search for new drugs has been greatly accelerated by the emergence of viruses and drug-resistant strains known pathogens. Nucleoside analogues (NAs) are a prospective class antivirals due to safety profiles, which important rapid repurposing in fight against emerging Recent improvements research methods have revealed unexpected details mechanisms action NAs that can pave way approaches further development effective drugs. This review accounts advanced techniques viral polymerase targeting, host enzyme targeting approaches, prodrug-based strategies antiviral NAs.

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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SARS-CoV-2: pathogenesis, therapeutics, variants, and vaccines

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: June 13, 2024

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in December with staggering economic fallout and human suffering. The unique structure of SARS-CoV-2 its underlying pathogenic mechanism were responsible for the global pandemic. In addition to direct damage virus, triggers an abnormal immune response leading a cytokine storm, culminating distress other fatal diseases that pose significant challenge clinicians. Therefore, potential treatments should focus not only on eliminating virus but also alleviating or controlling immune/inflammatory responses. Current management strategies COVID-19 include preventative measures supportive care, while role host progression has largely been overlooked. Understanding interaction between receptors, as well pathogenesis, proven be helpful prevention, early recognition progression, vaccine development, interventions aimed at reducing immunopathology have shown reduce adverse clinical outcomes improve prognosis. Moreover, several key mutations genome sequence result enhanced binding affinity cell receptor, produce escape, either increased transmissibility virulence variants carry these mutations. This review characterizes structural features SARS-CoV-2, variants, their system, emphasizing dysfunctional responses storm progression. Additionally, therapeutic options are reviewed, providing critical insights into management, exploring effective approaches deal public health crises SARS-CoV-2.

Language: Английский

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Emerging drug design strategies in anti-influenza drug discovery

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(12), P. 4715 - 4732

Published: Aug. 14, 2023

Influenza is an acute respiratory infection caused by influenza viruses (IFV), According to the World Health Organization (WHO), seasonal IFV epidemics result in approximately 3–5 million cases of severe illness, leading about half a deaths worldwide, along with economic losses and social burdens. Unfortunately, frequent mutations lead certain lag vaccine development as well resistance existing antiviral drugs. Therefore, it great importance develop anti-IFV drugs high efficiency against wild-type resistant strains, needed fight current future outbreaks different strains. In this review, we summarize general strategies used for discovery agents targeting multiple strains (including those available drugs). Structure-based drug design, mechanism-based multivalent interaction-based design repurposing are amongst most relevant that provide framework IFV.

Language: Английский

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Inhibitors of Nucleotide Biosynthesis as Candidates for a Wide Spectrum of Antiviral Chemotherapy

Microorganisms, Journal Year: 2022, Volume and Issue: 10(8), P. 1631 - 1631

Published: Aug. 12, 2022

Emerging and re-emerging viruses have been a challenge in public health recent decades. Host-targeted antivirals (HTA) directed at cellular molecules or pathways involved virus multiplication represent an interesting strategy to combat presently lacking effective chemotherapy. HTA could provide wide range of agents with inhibitory activity against current future that share similar host requirements reduce the possible selection antiviral-resistant variants. Nucleotide metabolism is one more exploited metabolic as potential antiviral target for several human viruses. This review focuses on properties inhibitors pyrimidine purine nucleotide biosynthesis, emphasis rate-limiting enzymes dihydroorotate dehydrogenase (DHODH) inosine monophosphate (IMPDH) which there are old new drugs active broad spectrum pathogenic

Language: Английский

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Antiviral Mechanism of Virucidal Sialic Acid Modified Cyclodextrin

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 582 - 582

Published: Feb. 9, 2023

We have reported that CD-6'SLN [6-sialyllactosamine (6'SLN)-modified β-cyclodextrin (CD)] can be a potential anti-influenza drug because it irreversibly deactivates virions. Indeed, in vivo, improved mice survival an H1N1 infection model even when administered 24 h post-infection. Although was designed to target the viral envelope protein hemagglutinin (HA), natural receptor of 6'SLN, remains unclear whether other targets exist. In this study, we confirm inhibits influenza virus through extracellular mechanism by interacting with HA, but not neuraminidase (NA), despite latter also having binding pocket for sialyl group. find interacts as elicits release fluorophore embedded membrane. Two similar compounds were test separately effect 6'SLN and undecyl moiety links CD 6'SLN. Neither showed any interaction membrane nor irreversible inhibition (virucidal), confirming both components are essential virucidal action. Unlike antiviral cyclodextrins developed against viruses, able decapsulate RNA. Our findings support combining protein-specific epitopes hydrophobic linkers provides strategy developing drugs mechanism.

Language: Английский

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New analytical method development and validation for estimation of molnupiravir in bulk and tablet dosage form by RP-HPLC method

Cellular Molecular and Biomedical Reports, Journal Year: 2023, Volume and Issue: 3(3), P. 130 - 136

Published: April 11, 2023

A new simple, selective, rapid, precise reversed-phase high-performance liquid chromatography method has been developed and validated for the estimation of Molnupiravir in bulk its pharmaceutical dosage form. The separation was made using Symmetry ODS C18 (4.6×150mm, 5µm) column. mobile phase used contained Methanol. Phosphate Buffer pH-4.2 adjusted with Orthophosphoric acid solution ratio 35:65% v/v an isocratic mode at a wavelength 236nm. mobile-phase flow rate sample volume injected were 1 ml/min 10 μL, respectively. retention time found to be 2.8 ±0.2mins. good linear relationship r =0.999) observed over concentration range 20 100µg/ml Molnupiravir. limit detection (LOD) quantification (LOQ) 2.6µg/ml 6.35µg/ml. recovery percentage 98-102%. relative standard deviation precision study <2%. is precise, specific, accurate making it suitable marketed It concluded that present RP- HPLC accurate, hence can routine quality control analysis Pharmaceutical industry.

Language: Английский

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