Antiviral Research, Journal Year: 2024, Volume and Issue: unknown, P. 106042 - 106042
Published: Nov. 1, 2024
Language: Английский
Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(4), P. 1060 - 1096
Published: March 12, 2024
Language: Английский
Citations
60
Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(2), P. 217 - 217
Published: Feb. 2, 2024
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms action some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. most effective drug approved date for treatment is PaxlovidTM, which combination two protease inhibitors, nirmatrelvir ritonavir. Nirmatrelvir reversible covalent peptidomimetic inhibitor main (Mpro) SARS-CoV-2, enzyme plays crucial role reproduction. In this combination, ritonavir serves as pharmacokinetic enhancer, it irreversibly inhibits cytochrome CYP3A4 responsible rapid metabolism nirmatrelvir, thereby increasing half-life bioavailability nirmatrelvir. tutorial review, we summarize development pharmaceutical chemistry aspects Paxlovid, covering evolution warhead design, synthesis mechanism well its inhibition mechanism. efficacy Paxlovid novel virus mutants also overviewed.
Language: Английский
Citations
17
Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)
Published: Jan. 15, 2025
Abstract We have assessed antiviral activity and induction of protective immunity fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The block infection cell lines lung-derived organotypic cultures. Intranasal administration allows maintenance homeostatic transcriptomic immune profile lungs, prevents body-weight loss, decreases viral load shedding, protects death caused by variants. Prolonged high-dose has neither adverse effects nor impairs peptide efficacy subsequent challenges. peptide-protected develop cross-reactive neutralizing antibodies against both used for initial recently circulating variants, are completely protected a second lethal infection, suggesting that they developed SARS-CoV-2-specific immunity. This strategy provides an additional approach global effort COVID-19 may contribute to development rapid responses emerging pathogenic viruses.
Language: Английский
Citations
1
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: March 5, 2025
The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. integration novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, artificial intelligence have significantly expedited the development groundbreaking drugs, effectively addressing obstacles associated with their character, such as rapid clearance degradation, necessitating subcutaneous injection leading increasing patient discomfort, ultimately advancing translational research efforts. Peptides are presently employed in management diagnosis diverse array medical conditions, diabetes mellitus, weight loss, oncology, rare diseases, additionally garnering interest facilitating targeted platforms advancement vaccines. This paper provides an overview present market clinical trial progress therapeutics, platforms, It examines key areas through literature analysis emphasizes structural modification principles well recent advancements screening, design, technologies. accelerated including peptide-drug complexes, new vaccines, innovative diagnostic reagents, has potential promote era precise customization disease therapeutic schedule.
Language: Английский
Citations
1
MedComm, Journal Year: 2024, Volume and Issue: 5(8)
Published: July 28, 2024
Abstract Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one the top priorities, especially in cases emergence mutant viruses inability current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, report its design strategy preclinical data. First, surprisingly found that IPB29 with rigid linker between peptide sequence lipid molecule had greatly improved α‐helical structure antiviral activity. Second, potently inhibited large panel SARS‐CoV‐2 variants including previously circulating viruses, such as Omicron XBB.5.1 EG.5.1. Third, could also cross‐neutralize bat‐ pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, PCoV‐GX) other human (SARS‐CoV, MERS‐CoV, HCoV‐NL63, HCoV‐229E). Fourth, administrated an inhalation solution (IPB29‐IS) Syrian hamsters exhibited high therapeutic preventive efficacies Delta or variant. Fifth, pharmacokinetic profiles safety pharmacology IPB29‐IS were extensively characterized, providing data support evaluation humans. conclusion, our studies demonstrated for fusion inhibitors offered ideal drug candidate coronaviruses.
Language: Английский
Citations
4
Biosafety and Health, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
0
Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106154 - 106154
Published: March 1, 2025
Language: Английский
Citations
0
PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1013034 - e1013034
Published: April 11, 2025
The persistent emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlights the need for developing broad-spectrum antiviral agents. Here, we report identification two sarbecovirus S2-specific alpaca nanobodies, namely H17 and H145, that effectively neutralize known SARS-CoV-2 (including Omicron subvariants) other sarbecoviruses (such as SARS-CoV, PANG/GD, WIV1, HKU3). nanobodies recognize a linear epitope (D 1139 PLQPELDSFKEEL 1152 ) in upper region S2 stem-helix (SH), which is highly conserved among sarbecoviruses. complex structure nanobody bound to SH-peptide reveal binding will impede refolding S2, neutralizing virus. Moreover, bind viral an acidification-insensitive manner, demonstrating their capacity entry inhibition especially when viruses enter via endosomal route. Finally, H145 possess better taking-action window virus neutralization, superior RBD-targeting exert neutralization by competing against ACE2 binding. Taken together, results suggest anti-SH are promising drug candidates preventing treating pandemic infections
Language: Английский
Citations
0
3 Biotech, Journal Year: 2025, Volume and Issue: 15(2)
Published: Jan. 13, 2025
Language: Английский
Citations
0
Heliyon, Journal Year: 2024, Volume and Issue: 10(9), P. e30489 - e30489
Published: April 29, 2024
The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known their safety, efficacy, selectivity, have recently emerged as promising candidates treating late-developing viral infections. In this study, three peptides were selected target different stages of invasion, specifically ACE2 S protein binding, well membrane fusion. objective was assess ability impede entry SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that combination these demonstrated enhanced antiviral effects. This outcome substantiates feasibility developing effective peptide combinations combat diseases related SARS-CoV-2. Moreover, three-peptide combinations, designed multiple aspects entry, exhibited heightened inhibition broad-spectrum properties.
Language: Английский
Citations
1