Influenza virus enzyme mechanism

Mechanism of Action An antiviral that appears to inhibit the influenza virus enzyme neuraminidase, which is essential for viral replication. Therapeutic Effect Prevents viral release from infected cells. 

Mechanism of Action A selective inhibitor of influenza virus neuraminidase, an enzyme essential for viral replication. Acts against both influenza A and B viruses. Therapeutic Effect Suppresses the spread of infect ion within the respiratory system and re-duces the duration of clinical symptoms. 

Mechanism of Action. Oseltamivir and zanamivir inhibit a specific enzyme (neuraminidase) that the influenza virus uses to complete its biosynthesis and release. By inhibiting this enzyme, these drugs impair a key step in viral replication, and reduce the ability of the virus to infect other respiratory cells. 

The antiviral properties of PAA against Herpes Simplex virus were discovered during routine screening (5), and these compounds also inhibit influenza virus replication (6). While the precise mode of action of PAA and PFA are not known at present, they will inhibit the polymerase enzymes in the two viruses. Two mechanisms for this inhibition appear plausible. 

The mechanism by which influenza virus sialidases cleaves the Neu5Ac(a2 3)Gal or Neu5Ac(a2- 6)Gal linkage has been a topic of much interest for many years (e.g., see [71, 72]). Recently, it has been shown by structural analysis [73] that it involves a covalent enzyme-substrate intermediate as has been reported for other sialidases. A proposed mechanism is depicted in Scheme 17.1. 

The exact mechanism of enzyme catalysis as well as the structural and energetic aspects of substrate and inhibitor binding have been studied with the aid of molecular modeling, based on the complex of Neu5Ac with influenza virus A/Tokyo/3/67 neuraminidase (Scheme 16.4) [74c]. 

The enzyme mechanism of NA of influenza virus has been investigated by kinetic isotope methods, NMR, and a molecular dynamics simulation of the enzyme-substrate complex. 

Similarly, Chong et al. [22] showed that a positively charged residue was involved in substrate binding and hydrolysed by an influenza virus NA. Using site-directed mutagenesis, Lentz et al. [23] identified amino acids involved in enzyme activity without the full knowledge of the NA three-dimensional structure. Although the enzyme mechanism proposed by Lentz is... 

MECHANISMS OE ACTION AND RESISTANCE Ribavirin alters cellular nucleotide pools and inhibits viral mRNA synthesis. Intracellular phosphorylation to the mono-, di-, and triphosphate derivatives is mediated by host cell enzymes. In both uninfected and RSV-infected cells, the predominant derivative is the triphosphate, which has an intracellular of <2 hours. Ribavirin monophosphate competitively inhibits cellular inosine-5 -phosphate dehydrogenase and interferes with the synthesis of GTP and thus nucleic acid synthesis. Ribavirin triphosphate also competitively inhibits the GTP-dependent 5 capping of viral messenger RNA and specifically influenza virus transcriptase activity. Ribavirin has multiple sites of action, and some of these e.g., inhibition of GTP synthesis) may potentiate others e.g., inhibition of GTP-dependent enzymes). Ribavirin also may enhance viral mutagenesis such that some viruses may be inhibited in effective replication, so-caUed lethal mutagenesis. 

M. (1995) Effect of substrate aglycon on enzyme mechanism in the reaction of sialidase from influenza virus. FEBS Letters, 372, 148-150. 

Ribavirin is a synthetic guanosine analogue that possesses broad antiviral inhibitory activity against many viruses, including influenza A and B, parainfluenza, RS V, HCV, HIV-1, and various herpesviruses, arenaviruses, and paramyxoviruses. Its exact mechanism of action has not been fully elucidated however, it appears to inhibit the synthesis of viral mRNA through an effect on nucleotide pools. Following absorption, host cell enzymes convert ribavirin to its monophosphate, diphosphate, and triphosphate forms. Ribavirin monophosphate... 

Ribavirin [13] is a guanosine analog that is intracellularly phosphorylated by the host cell s enzymes. Despite its mechanism is not yet fully elucidated, it apparently interferes with the synthesis of guanosine triphosphate to inhibit capping of viral mRNA and some viral RNA-dependent polymerases. Its triphosphate derivative inhibits the replication of a wide range of RNA and DNA viruses including influenza A and B, parainfluenza, respiratory syncytial virus (RSV), paramyxovirus, HCV and HIV-1. 

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