ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(15)
Published: April 15, 2024
Abstract This review article aims to significantly advance the scientific community's efforts develop effective nucleoside‐based drugs for treating severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 ) and other emerging infectious diseases. study concentrates on main viral protease (Mpro) explores compounds as potential therapeutic agents. investigation investigated impact of acylation‐induced modifications nucleoside hydroxyl group subsequent properties. Nucleoside analogs, which are recognized their diverse biochemical properties, were synthesized rigorously screened evaluate antimicrobial efficacy. In domain pharmaceutical research, computational pharmacokinetics has emerged a critical tool, especially in pursuit analogs therapeutics. silico methods aid predicting pharmacokinetic traits, interactions with crucial enzymes, stability these biological environments, thereby streamlining drug design reducing experimental costs. Concurrently, studies revealed intricate between active site protease. The amalgamation screening insights underscores emergence potent candidates inhibitory activity against SARS‐CoV‐2 M pro . Additionally, this integrates that provide valuable into SARS‐CoV‐2.
Language: Английский
Citations
25Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2
RSC Advances, Journal Year: 2023, Volume and Issue: 13(50), P. 35500 - 35524
Published: Jan. 1, 2023
The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in world healthcare system. Despite some progress creation of antiviral vaccines and mass vaccination population, number patients continues grow because spread new mutations. There is an urgent need for direct-acting drugs capable suppressing or stopping main mechanisms reproduction SARS-CoV-2. Several studies have shown that successful replication virus cell requires proteolytic cleavage protein structures virus. Two proteases are crucial replicating other coronaviruses: protease (Mpro) papain-like (PLpro). In this review, we summarize essential viral proteins required its life cycle as targets chemotherapy infection provide critical summary development against COVID-19 from drug repurposing strategy up molecular design novel covalent non-covalent agents inhibiting replication. We overview choice Mpro PLpro promising pharmacological impact on cycle.
Language: Английский
Citations
10Transcription Kinetics in the Coronavirus Life Cycle
Wiley Interdisciplinary Reviews - RNA, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 1, 2025
Coronaviruses utilize a positive-sense single-strand RNA, functioning simultaneously as mRNA and the genome. An RNA-dependent RNA polymerase (RdRP) plays dual role in transcribing genes replicating genome, making RdRP critical target therapies against coronaviruses. This review explores recent advancements understanding coronavirus transcription machinery, discusses it within virus infection context, incorporates kinetic considerations on activity. We also address steric limitations replication, particularly during early phases, outline hypothesis regarding translation-transcription conflicts, postulating existence of mechanisms that resolve these issues. In cells infected by coronaviruses, abundant structural proteins are synthesized from subgenomic fragments (sgRNAs) produced via discontinuous transcription. During elongation, can skip large sections viral resulting creation shorter sgRNAs reflects stoichiometry proteins. Although precise mechanism remains unknown, we discuss hypotheses involving long-distance RNA-RNA interactions, helicase-mediated backtracking, dissociation reassociation RdRP, dimerization.
Language: Английский
Citations
0Antivirals in COVID‐19: A Focus on Pediatric Cardiac Patients
Canadian Journal of Infectious Diseases and Medical Microbiology, Journal Year: 2025, Volume and Issue: 2025(1)
Published: Jan. 1, 2025
The COVID‐19 pandemic created an unprecedented public health crisis, driven by its rapid global spread and the urgent need for worldwide collaborative interventions to contain it. This urgency spurred search therapeutic agents prevent or manage infection. Among these, various types of antivirals emerged as a prominent treatment option, supported wealth observational studies randomized controlled trials. results from such conflict, with some concluding efficacy others lack thereof, variability also occurring depending on severity in studied population. In addition, many have been explored using trials—the gold standard evaluating intervention—to only limited degree, most evidence behind their use concluded studies. Thus, sheer volume data has made it challenging resolve inconsistencies determine true efficacy. Furthermore, there is paucity literature regarding pediatric population infected COVID‐19, being extrapolated done adult patients. As such, additional trials are needed solidify effectiveness managing particularly underexplored especially vulnerable cardiac Therefore, utilizing trials, this narrative review evaluates rationale antivirals, summarizes findings literature, concludes focused discussion application
Language: Английский
Citations
0Assessing the Potential Contribution of In Silico Studies in Discovering Drug Candidates That Interact with Various SARS-CoV-2 Receptors
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15518 - 15518
Published: Oct. 24, 2023
The COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly search candidates that interact with various SARS-CoV-2 receptors. These involve use of computer simulations and computational algorithms predict potential interaction target primary receptors targeted by include RNA polymerase, main protease, spike protein, ACE2 receptor, transmembrane protease serine 2 (TMPRSS2). identified several promising candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, Camostat Mesylate, among others. offers advantages, ability screen large number relatively short amount time, thereby reducing time cost involved traditional methods. Additionally, allow prediction binding affinity receptors, providing insight into their efficacy. This study is aimed at assessing useful contributions application instruments It further highlights some advantages limitations these studies, revealing complementary experimental validation ensure efficacy safety candidates.
Language: Английский
Citations
9Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies
Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5564 - 5564
Published: Nov. 25, 2024
Amidst the ongoing global challenge of SARS-CoV-2 pandemic, quest for effective antiviral medications remains paramount. This comprehensive review delves into dynamic landscape FDA-approved repurposed COVID-19, categorized as and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, future outlooks. Unveiling genomic intricacies variants, including WHO-designated Omicron variant, we explore diverse categories such fusion inhibitors, protease transcription neuraminidase nucleoside reverse transcriptase, interventions like importin α/β1-mediated nuclear import neutralizing antibodies, convalescent plasma. Notably, Molnupiravir emerges a pivotal player, now licensed in UK. offers fresh perspective on historical evolution COVID-19 therapeutics, from endeavors to latest developments oral anti-SARS-CoV-2 treatments, ushering new era hope battle against pandemic.
Language: Английский
Citations
1PrimPol-mediated repriming elicits gap-filling by template switching and promotes cellular tolerance to Cidofovir
DNA repair, Journal Year: 2024, Volume and Issue: 145, P. 103787 - 103787
Published: Nov. 14, 2024
Language: Английский
Citations
0
Published: Dec. 27, 2024
Language: Английский
Citations
0