Published: Jan. 1, 2024
Language: Английский
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1481 - 1481
Published: Feb. 10, 2025
Respiratory viral infections present significant global health challenges, causing substantial morbidity and mortality, particularly among highly susceptible components of the population. The emergence pandemics epidemics, such as those caused by influenza viruses coronaviruses, emphasizes urgent need for effective antiviral therapeutics. In this review, we explore potential broad-spectrum agents targeting respiratory RNA viruses, including syncytial virus, human metapneumovirus, parainfluenza rhinoviruses. Various direct-acting host-targeting antivirals are discussed, monoclonal antibodies conserved regions surface proteins, molecules interfering with host cell receptors or replication machinery, protease inhibitors, siRNA therapies, ribonuclease, 3D8 scFv. Advancements in approaches to reduce resistance RNA-based therapeutics offer combating threats. Despite represent a crucial strategy, when specific pathogens unidentified rapid intervention is essential, during outbreaks.
Language: Английский
Citations
3
Antiviral Research, Journal Year: 2025, Volume and Issue: 236, P. 106118 - 106118
Published: Feb. 17, 2025
Language: Английский
Citations
2
Diagnostic Microbiology and Infectious Disease, Journal Year: 2025, Volume and Issue: 111(3), P. 116707 - 116707
Published: Jan. 21, 2025
Language: Английский
Citations
1
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Feb. 1, 2025
SARS-CoV-2 main protease, Mpro, is responsible for processing the viral polyproteins into individual proteins, including protease itself. Mpro a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component Paxlovid). Resistance mutants identified clinically and in passage assays contain combination site mutations (e.g., E166V, E166A, L167F), which reduce inhibitor binding enzymatic activity, non-active P252L, T21I, L50F), restore fitness replication. To probe role rescue, here we use an triple mutant (L50F/E166A/L167F) that confers drug resistance with level similar to wild-type. By comparing peptide full-length protein substrates, demonstrate substrate involves more than residues site. Particularly, L50F other can enhance dimer-dimer interactions help place nsp5-6 at enzyme catalytic center. The structural activity data L50F, L50F/E166A/L167F, others underscore importance considering whole studying interactions, offers important insights function, development, design.
Language: Английский
Citations
1
Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 17 - 17
Published: Dec. 28, 2024
The COVID-19 pandemic, driven by the rapid evolution of SARS-CoV-2 virus, presents ongoing challenges to global public health. is characterized rapidly evolving mutations, especially in (but not limited to) spike protein, complicating predictions about its evolutionary trajectory. These mutations have significantly affected transmissibility, immune evasion, and vaccine efficacy, leading multiple pandemic waves with over half a billion cases seven million deaths globally. Despite several strategies, from development administration design availability antivirals, including monoclonal antibodies, already having been employed, persistent circulation virus emergence new variants continue result high case numbers fatalities. In past four years, immense research efforts contributed much our understanding viral pathogenesis mechanism, syndrome, host-microbe interactions, effective vaccines, diagnostic tools, treatments. focus this review provide comprehensive analysis functional impact on diagnosis, treatments, effectiveness. We further discuss safety pregnancy implications hybrid immunity long-term protection against infection, as well latest developments pan-coronavirus nasal formulations, emphasizing need for continued surveillance, research, adaptive health strategies response race.
Language: Английский
Citations
4
Journal of Antimicrobial Chemotherapy, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 13, 2025
Abstract Background Persistent COVID-19 (pCOVID-19) in immunocompromised patients is characterized by unspecific symptoms and pulmonary infiltrates due to ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication. Treatment options remain unclear, leading different approaches, including combination therapy extended durations. The purpose of this study was assess the efficacy safety antiviral therapies for pCOVID-19 since Omicron surge. Methods We searched MEDLINE Scopus from 1 January 2022 6 August 2024 cohort studies case series on nirmatrelvir/ritonavir, remdesivir, ensitrelvir molnupiravir. Evidence certainty rated using Grading Recommendations Assessment, Development, Evaluation outcomes viral clearance, recurrence/relapse, mortality, adverse events (AEs) symptom resolution. Results Thirteen involving 127 cases were included. very low. In with at least two direct agents, clearance 79%, a 16% recurrence rate. All-cause mortality 9%, 6% while SARS-CoV-2 positive. 47 cases, AEs reported 11%. Symptom resolution ranged 3 days studies. one agent passive immunization, 89%, an 11% rate no deaths. four documented observed. monotherapy, 100%, 15% One death, unrelated SARS-CoV-2, occurred. 12 Conclusions Based low evidence, combining immunization resulted high rates few recurrences. occurred treated antivirals. Controlled are needed.
Language: Английский
Citations
0
Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110967 - 110967
Published: Feb. 1, 2025
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: Feb. 21, 2025
The present work investigates virucidal and antiviral compounds in the extracts of seed embryos a lotus, Nelumbo nucifera, Thai ginseng, Kaempferia parviflora. Separation led to identification against SARS-CoV-2. Neferine (1) nuciferine (3) from N. as well their respective HCl salts (2 4), exhibited activities Virucidal activity neferine salt (2) (EC50 4.78 µM) was 7.5 times better than its free-base, 36.01 µM), also improved selectivity index (SI), showing less cytotoxicity 1. This demonstrates that organic have an impact on biological activities. A crude extract K. parviflora rhizomes displayed 42.11 µg/mL) 39.28 µg/mL). Isolation nine flavonoids (5–13). Among these flavonoids, only 5,7,4'-trimethoxyflavone (8) found show 437.90 50.97 However, (5–13) did not inhibit SARS-CoV-2 3CLpro enzyme at concentrations 10 µM 100 µM. In conclusion, our data underscores therapeutic potential nucifera derived bioactive
Language: Английский
Citations
0
Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106138 - 106138
Published: March 1, 2025
Viral respiratory infections remain a major and recurrent public health threat. Among them, influenza viruses are responsible for ⁓500,000 deaths worldwide high economic burden. The threat of emerging zoonotic or pandemic worsens this scenario, being SARS-CoV-2 the millions COVID-19 most recent example. rapid evolution circulating allows emergence dissemination variant strains carrying mutations resulting in suboptimal vaccine protection and/or reduced efficacy current limited therapeutic arsenal. In context, host-targeted approaches constitute promising antiviral strategy aiming to achieve broad-spectrum activity mitigate viral resistance against classic direct acting antivirals. Here, we demonstrated that diltiazem, calcium channel blocker currently used treat angor, induces an ISG expression profile characteristic cellular state mainly driven by IFN-λ. We then evaluated potential diltiazem-baloxavir combination Influenza A wild-type PA I38T resistant strain cell culture human airway epithelia (HAE). analogously diltiazem-molnupiravir SARS-CoV-2, including variants concern. Our results demonstrate diltiazem viruses, strains, as well capacity potentiate effect baloxavir. further production protected integrity HAE infected with SARS-CoV-2. This study highlights interest combining agents viruses.
Language: Английский
Citations
0
Journal of Chemical Research, Journal Year: 2025, Volume and Issue: 49(2)
Published: March 1, 2025
The repercussions of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are catastrophic, and world has yet to achieve full recovery. Several inhibitors targeting SARS-CoV-2 main protease experiencing diminished efficacy owing resistance-inducing mutations. current situation implies that quest find potent resilient drugs overcome resistance must be a continuous effort. Here, multiple receptor virtual screening molecular dynamics (MD) simulation techniques were employed identify novel binders from an integrated small-molecule database as leads for discovery, design, development antivirals immune protease. was initially screened separately against five structures with different substrate-binding site conformations using GOLD program, after which fitness score control compound used cutoff create shortlist potential hits in each case. Then, 21 compounds at intersection all shortlists selected hits. subjected MD simulations, identifying four capable remaining bound up 100 ns. Analysis mode binding interactions between revealed fit better into conserved subpockets than interact important amino acid residues. Conjointly, energy, toxicity analysis results further demonstrated promising augment fight resistance.
Language: Английский
Citations
0