tetano
Editor, Senior Moderator
Chem Biodivers
. 2023 Jun 28;e202201077.
doi: 10.1002/cbdv.202201077. Online ahead of print. In Silico Design of an Oseltamivir Derivative with Increased Affinity against Wild-Type and Mutant Variants of Neuraminidase and Hemagglutinin of Influenza A H1N1 Virus
García-Machorro Jazmin[SUP] 1 [/SUP], Mirzaeicheshmeh Elaheh[SUP] 1 2 [/SUP], Fragoso-Vázquez Manuel Jonathan[SUP] 3 [/SUP], Bello Martiniano[SUP] 2 [/SUP], Méndez-Luna David[SUP] 2 4 [/SUP], León-Cardona Alám[SUP] 2 [/SUP], Correa-Basurto José[SUP] 2 [/SUP]
Affiliations
Antiviral resistance has turned into a world concern nowadays. Influenza A H1N1 emerged as a problem at the world level due to the neuraminidase (NA) mutations. The NA mutants conferred resistance to oseltamivir and zanamivir. Several efforts were conducted to develop better anti-influenza A H1N1 drugs. Our research group combined in silico methods to create a compound derived from oseltamivir to be tested in vitro against influenza A H1N1. Here we show the results of a new compound derived from oseltamivir but with specific chemical modifications, with significant affinity either on NA (in silico and in vitro assays) or HA (in silico) from influenza A H1N1 strain. We include docking and molecular dynamics (MD) simulations of the oseltamivir derivative at the binding site onto NA and HA of influenza A H1N1. Additionally, the biological experimental results show that oseltamivir derivative decreases the lytic-plaque formation on viral susceptibility assays, and it does not show cytotoxicity. Finally, oseltamivir derivative assayed on viral NA showed a concentration-dependent inhibition behavior at nM, depicting a high affinity of the compound for the enzyme, corroborated with the MD simulations results, placing our designed oseltamivir derivative as a potential antiviral against influenza A H1N1.
Keywords: H1N1; antivirals; drug design; neuraminidase.
. 2023 Jun 28;e202201077.
doi: 10.1002/cbdv.202201077. Online ahead of print. In Silico Design of an Oseltamivir Derivative with Increased Affinity against Wild-Type and Mutant Variants of Neuraminidase and Hemagglutinin of Influenza A H1N1 Virus
García-Machorro Jazmin[SUP] 1 [/SUP], Mirzaeicheshmeh Elaheh[SUP] 1 2 [/SUP], Fragoso-Vázquez Manuel Jonathan[SUP] 3 [/SUP], Bello Martiniano[SUP] 2 [/SUP], Méndez-Luna David[SUP] 2 4 [/SUP], León-Cardona Alám[SUP] 2 [/SUP], Correa-Basurto José[SUP] 2 [/SUP]
Affiliations
- PMID: 37377353
- DOI: 10.1002/cbdv.202201077
Antiviral resistance has turned into a world concern nowadays. Influenza A H1N1 emerged as a problem at the world level due to the neuraminidase (NA) mutations. The NA mutants conferred resistance to oseltamivir and zanamivir. Several efforts were conducted to develop better anti-influenza A H1N1 drugs. Our research group combined in silico methods to create a compound derived from oseltamivir to be tested in vitro against influenza A H1N1. Here we show the results of a new compound derived from oseltamivir but with specific chemical modifications, with significant affinity either on NA (in silico and in vitro assays) or HA (in silico) from influenza A H1N1 strain. We include docking and molecular dynamics (MD) simulations of the oseltamivir derivative at the binding site onto NA and HA of influenza A H1N1. Additionally, the biological experimental results show that oseltamivir derivative decreases the lytic-plaque formation on viral susceptibility assays, and it does not show cytotoxicity. Finally, oseltamivir derivative assayed on viral NA showed a concentration-dependent inhibition behavior at nM, depicting a high affinity of the compound for the enzyme, corroborated with the MD simulations results, placing our designed oseltamivir derivative as a potential antiviral against influenza A H1N1.
Keywords: H1N1; antivirals; drug design; neuraminidase.