How Much Potential Do Nucleoside Analogs Offer to Combat Human Corona Viruses? DOI Creative Commons
Włodzimierz Buchowicz, Mariola Koszytkowska‐Stawińska

Organics, Год журнала: 2024, Номер 5(2), С. 71 - 110

Опубликована: Май 8, 2024

Nucleoside analogs (NAs) have been extensively examined as plausible antiviral agents in recent years, particular since the outbreak of global pandemic COVID-19 2019. In this review, structures and properties over 450 NAs are collected according to type virus, namely SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL63. The activity against HCoV-related enzymes is also presented. Selected studies dealing with mode action discussed detail. repurposing known appears be most investigated scientific approach towards efficacious anti-HCoV agents. recently reported de novo-designed seem open up additional approaches new drug candidates.

Язык: Английский

A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein DOI Creative Commons
Ellen Van Damme, Pravien Abeywickrema, Yanting Yin

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Abstract The membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly 1,2 . Here we describe the identification JNJ-9676, small-molecule inhibitor targeting coronavirus M protein. JNJ-9676 demonstrates vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV sarbecovirus strains from bat pangolin zoonotic origin. Using cryogenic electron microscopy (cryo-EM), determined binding pocket formed by transmembrane domains dimer. Compound stabilized dimer an altered conformational state between its long short forms, preventing release infectious virus. In pre-exposure Syrian golden hamster model, (25 mg per kg twice day) showed excellent efficacy, illustrated significant reduction load virus lung 3.5 4 log 10 -transformed RNA copies 50% tissue culture infective dose (TCID 50 ) lung, respectively. Histopathology scores at this were reduced to baseline. post-exposure was efficacious 75 day even when added 48 h after infection, peak loads observed. attractive target block replication, represents interesting chemical series towards identifying clinical candidates addressing current future pandemics.

Язык: Английский

Процитировано

1
Efficacy and safety of antiviral treatments for symptomatic COVID-19 outpatients: network meta-analysis and budget impact analysis DOI Creative Commons

Giacomo Berti,

Daniele Mengato, Honoria Ocagli

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

Remdesivir (RDV) and nirmatrelvir/ritonavir (NRM/RTV) are two antiviral agents for treating outpatient adults with mild to moderate symptomatic COVID-19 at high risk of developing a severe disease. The review objectives compare the efficacy safety these antivirals based on published RCT real-world data, evaluate costs from healthcare perspective. This study provides network meta-analysis RDV NRM/RTV early treatment COVID-19. outcomes analysed were hospitalisation any cause serious adverse events. A cost-analysis was performed incorporating drug costs, administration, hospitalisations, management budget impact analysis estimated University Hospital Padua. Our results indicated that showed trend towards lower compared (RR 1.59, 95% CI: 0.60-4.20), though this not statistically significant. For safety, demonstrated slightly events 0.92, 0.31-2.74), but without statistical significance. cost could save €550,854.46 per 1,000 patients. Finally, data Padua annual savings €210,977.25 if all treatments administered instead RDV. comparison therapies did yield significant differences in potential prevent or However, saving favour NRM/RTV.

Язык: Английский

Процитировано

0
Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase DOI Creative Commons
Zherui Zhang, Hongqing Zhang, Yanan Zhang

и другие.

Virologica Sinica, Год журнала: 2023, Номер 38(3), С. 470 - 479

Опубликована: Апрель 30, 2023

COVID-19 has become a global public health crisis since its outbreak in China December 2019. Currently there are few clinically effective drugs to combat SARS-CoV-2 infection. The main protein (M

Язык: Английский

Процитировано

10
Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116) DOI
Qiuyu Cao, Yi Ding, Yu Xu

и другие.

Frontiers of Medicine, Год журнала: 2023, Номер 17(6), С. 1068 - 1079

Опубликована: Дек. 1, 2023

Язык: Английский

Процитировано

7
Remdesivir Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal Coronaviruses DOI Creative Commons
Weiyong Liu, Min Zhang,

Chieh-Ju Hu

и другие.

Viruses, Год журнала: 2023, Номер 15(12), С. 2295 - 2295

Опубликована: Ноя. 23, 2023

Coronaviruses represent a significant threat to both human and animal health, encompassing range of pathogenic strains responsible for illnesses, from the common cold more severe diseases. VV116 is deuterated derivative Remdesivir with oral bioavailability that was found potently inhibit SARS-CoV-2. In this work, we investigated broad-spectrum antiviral activity against variety coronaviruses. We examined inhibitory effects on replication coronaviruses HCoV-NL63, HCoV-229E, HCoV-OC43, as well MHV, FIPV, FECV, CCoV. The findings reveal effectively inhibits viral across these without exhibiting cytotoxicity, indicating its potential safe therapeutic use. Based results time-of-addition assay an rNTP competitive inhibition assay, it speculated mechanism HCoV-NL63 consistent Our work presents promising candidate anti-coronavirus therapy, implications supports expansion applications backed by detailed experimental data.

Язык: Английский

Процитировано

6
A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein DOI Creative Commons
Marnix Van Loock, Ellen Van Damme, Pravien Abeywickrema

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Март 7, 2024

Abstract The membrane (M) protein of betacoronaviruses is well-conserved and plays a key role in viral assembly. Here, we describe the discovery JNJ-9676, novel small molecule targeting coronaviral (CoV) M protein. JNJ-9676 demonstrates in vitro nanomolar antiviral activity against SARS-CoV2, SARS-CoV, sarbecovirus strains from bat pangolin zoonotic origin. Using cryogenic electron microscopy, determined binding pocket protein's transmembrane domain. Compound stabilized an altered conformational state between its long- short-forms, preventing release infectious virus. In pre-exposure Syrian golden hamster model, (25 mg/kg BID) showed excellent efficacy illustrated by significant reduction load virus lung 3.5 log10 4 log10, respectively. Histopathology scores at this dose were reduced to baseline. post-exposure was efficacious 75mg/kg BID even when added 48 h post-infection, peak loads observed. attractive target block coronavirus replication with representing interesting chemical series towards identifying clinical candidates addressing current future CoV pandemics.

Язык: Английский

Процитировано

1
How Much Potential Do Nucleoside Analogs Offer to Combat Human Corona Viruses? DOI Creative Commons
Włodzimierz Buchowicz, Mariola Koszytkowska‐Stawińska

Organics, Год журнала: 2024, Номер 5(2), С. 71 - 110

Опубликована: Май 8, 2024

Nucleoside analogs (NAs) have been extensively examined as plausible antiviral agents in recent years, particular since the outbreak of global pandemic COVID-19 2019. In this review, structures and properties over 450 NAs are collected according to type virus, namely SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-NL63. The activity against HCoV-related enzymes is also presented. Selected studies dealing with mode action discussed detail. repurposing known appears be most investigated scientific approach towards efficacious anti-HCoV agents. recently reported de novo-designed seem open up additional approaches new drug candidates.

Язык: Английский

Процитировано

0