Oral Antiviral Treatment for COVID-19: A Comprehensive Review on Nirmatrelvir/Ritonavir

Viruses, Journal Year: 2022, Volume and Issue: 14(11), P. 2540 - 2540

Published: Nov. 17, 2022

Despite the rapid development of efficient and safe vaccines against COVID-19, need to confine pandemic treat infected individuals on an outpatient basis has led approval oral antiviral agents. Taking into account viral kinetic pattern SARS-CoV-2, it is high importance intervene at early stages disease. A protease inhibitor called nirmatrelvir coupled with ritonavir (NMV/r), which acts as a CYP3A inhibitor, delivered formulation, shown much promise in preventing disease progression high-risk patients no for supplemental oxygen administration. Real-world data seem confirm drug combination’s efficacy safety all variants concern adult populations. Although, not fully clarified, rebound recurrence COVID-19 symptoms have been described following treatment; however, more potential resistance issues concerning Mpro gene, drug’s therapeutic target, are needed. NMV/r gamechanger fight by hospitalizations halting severity; therefore, research future greater awareness its use warranted.

Language: Английский

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Allosteric Binding Sites of the SARS-CoV-2 Main Protease: Potential Targets for Broad-Spectrum Anti-Coronavirus Agents

Drug Design Development and Therapy, Journal Year: 2022, Volume and Issue: Volume 16, P. 2463 - 2478

Published: Aug. 1, 2022

Abstract: The current pandemic caused by the COVID-19 disease has reached everywhere in world and affected every aspect of our lives. As data, World Health Organization (WHO) reported more than 300 million confirmed cases worldwide 5 deaths. M pro is an enzyme that plays a key role life cycle SARS-CoV-2 virus, it vital for progression. seems to have several allosteric sites can hinder catalytic activity. Furthermore, some these are located at or nearby dimerization interface which essential overall In this review paper, we investigate potential site act as drug target, especially since they interestingly appear be resistant mutation. work illustrated through three subsequent sections: First, two main categories been explained discussed. Second, total six pockets studied evaluated their druggability cavity characteristics. Third, experimental computational attempts discovery new inhibitors To sum up, paper gives detailed insight into feasibility developing treatment disease. Graphical Keywords: COVID-19, , SARS-CoV-2, sites, druggability, antiviral

Language: Английский

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What are the current anti-COVID-19 drugs? From traditional to smart molecular mechanisms

Virology Journal, Journal Year: 2023, Volume and Issue: 20(1)

Published: Oct. 24, 2023

Abstract Background Coronavirus disease 19 (COVID-19) is the caused by SARS-CoV-2, a highly infectious member of coronavirus family, which emerged in December 2019 “Wuhan, China”. It induces respiratory illness ranging from mild symptoms to severe disease. was declared “pandemic” World Health Organization (WHO) March 2020. Since then, vast number clinical and experimental studies have been conducted identify effective approaches for its prevention treatment. Main body The pathophysiology COVID-19 represents an unprecedented challenge; it triggers strong immune response, may be exacerbated “a cytokine storm syndrome”. also thrombogenesis trigger multi-organ injury. Therefore, different drug classes proposed treatment prevention, such as antivirals, anti-SARS-CoV-2 antibody agents (monoclonal antibodies, convalescent plasma, immunoglobulins), anti-inflammatory drugs, immunomodulators, anticoagulant drugs. To best our knowledge, this review first present, discuss, summarize current knowledge about used COVID-19, with special emphasis on their targets, mechanisms action, important adverse effects interactions. Additionally, we spotlight latest “October 2023” guidelines (NIH, IDSA, NICE) FDA approval or authorization regarding use these management COVID-19. Conclusion Despite wide array therapeutic strategies introduced one most prominent challenges SARS-CoV-2 mutations emerging new variants subvariants. Currently, anti-COVID-19 pipeline continuously affording novel treatments face growing challenge.

Language: Английский

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Structural and Mechanistic Insights into the Main Protease (Mpro) Dimer Interface Destabilization Inhibitor: Unveiling New Therapeutic Avenues against SARS-CoV-2

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

SARS-CoV-2 variant recurrence has emphasized the imperative prerequisite for effective antivirals. The main protease (Mpro) of is crucial viral replication, making it one prime and promising antiviral targets. Mpro features several druggable sites, including active sites allosteric near dimerization interface, that regulate its catalytic activity. This study identified six highly efficacious compounds (WIN-62577, KT185, bexarotene, ledipasvir, diacerein, simepervir) using structure-based virtual screening compound libraries against Mpro. Using SPR ITC, binding selected inhibitory to target was validated. FRET-based assay demonstrated molecules effectively inhibit with IC50 values in range from 0.64 11.98 μM. Additionally, vitro cell-based assays showed high efficacy EC50 1.51 18.92 crystal structure Mpro-minocycline complex detailed possible inhibition mechanism minocycline, an FDA-approved antibiotic. Minocycline binds site, revealing residues critical loss activity due destabilization molecular interactions at dimeric which are proteolytic suggests minocycline site may play a role dimer direct rational design derivatives as drugs.

Language: Английский

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Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods

Aspects of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100080 - 100080

Published: March 1, 2025

Language: Английский

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Flavonoids derived from medicinal plants as a COVID‐19 treatment

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(3), P. 1589 - 1609

Published: Jan. 29, 2024

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes COVID‐19 disease. Through its viral spike (S) protein, the virus enters and infects epithelial cells by utilizing angiotensin‐converting enzyme as a host cell's receptor protein. pandemic had profound impact on global public health economies. Although various effective vaccinations medications are now available to prevent treat COVID‐19, natural compounds derived from medicinal plants, particularly flavonoids, demonstrated therapeutic potential Flavonoids exhibit dual antiviral mechanisms: direct interference with invasion inhibition of replication. Specifically, they target key molecules, proteases, involved in infection. These showcase significant immunomodulatory anti‐inflammatory properties, effectively inhibiting inflammatory cytokines. Additionally, emerging evidence supports flavonoids mitigate progression individuals obesity positively influencing lipid metabolism. This review aims elucidate molecular structure SARS‐CoV‐2 underlying mechanism action virus. study evaluates anti‐SARS‐CoV‐2 properties exhibited flavonoid compounds, specific interest their mechanisms action, applications for prevention treatment COVID‐19. Nevertheless, portion existing knowledge is based theoretical frameworks findings vitro investigations. Further research required better assess effectiveness combating SARS‐CoV‐2, particular emphasis vivo clinical

Language: Английский

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Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N -(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: April 24, 2023

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt improve their biological availability and antiviral activity. Next, both cytotoxicity anti-SARS-CoV-2 activities of examined compounds loaded EMLs (F3a-g) assessed Vero E6 cells via MTT assay calculate CC50 inhibitory concentration 50 (IC50) values. The most potent 3e-loaded (F3e) elicited a selectivity index 18 with IC50 value 0.73 μg/mL. Moreover, F3e was selected for further elucidation possible mode action where results showed that it exhibited combination virucidal (>90%), viral adsorption (>80%), replication (>60%) inhibition. Besides, molecular docking MD simulations towards SARS-CoV-2 Mpro performed. Finally, structure-activity relationship (SAR) study focussed on studying influence altering size, type, flexibility α-substituent carboxamide addition compound contraction activity.HighlightsEmulsomes (3a-3g).The μg/mL against SARS-CoV-2.F3e inhibition.Molecular docking, dynamics (MD) simulations, MM-GBSA calculations performed.Structure-activity discussed

Language: Английский

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In silico screening of phenylethanoid glycosides, a class of pharmacologically active compounds as natural inhibitors of SARS-CoV-2 proteases

Computational and Structural Biotechnology Journal, Journal Year: 2023, Volume and Issue: 21, P. 1461 - 1472

Published: Jan. 1, 2023

Since the advent of Covid-19, several natural products have been investigated regarding their in silico interactions with SARS-CoV-2 proteases - 3CLpro and PLpro, two most important pharmacological targets for antiviral development. Phenylethanoid glycosides (PG) are a class present medicinal plants drug containing this group active ingredients has successfully used treatment Covid-19 China. Thus, dataset 567 derivatives was built from reviews published between 1994 2020, interaction against both investigated. The virtual screening performed by filtering PGs through evaluation scores based on AutoDock Vina, GOLD/ChemPLP, GOLD/GoldScore functions. bRO5 pharmacokinetic parameters ranked previous step were analyzed key amino acid residues PLpro enzymes evaluated. Ninety-eight compounds identified computational approaches 80 3CLpro. Of these, four interacted catalytic which is an indicative inhibitory activity, three five occur Traditional Chinese Medicine (TCM), while components plants/formulations currently protocols data presented here show potential as selective inhibitors PLpro.

Language: Английский

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Review of the Crystallized Structures of the SARS-CoV-2 papain-like protease

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141730 - 141730

Published: Feb. 1, 2025

Language: Английский

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Natural inhibitors of SARS-CoV-2 main protease: structure based pharmacophore modeling, molecular docking and molecular dynamic simulation studies

Journal of Molecular Modeling, Journal Year: 2022, Volume and Issue: 28(9)

Published: Aug. 29, 2022

Language: Английский

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