SARS-CoV-2 can evade Paxlovid by multiple mechanisms SARSCoV2 Coronavirus Disease COVID nirmatrelvir Paxlovid E166Q biorxivpreprint RutgersU USouthFlorida CatholicUniv
Study: Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. Image Credit: Orpheus FX / Shutterstock
About the study The present work sought to discover Mpro drug-resistant SARS-CoV-2 mutants associated with naturally occurring polymorphisms. The researchers examined the SARS-CoV-2 sequences in the Global Initiative on Sharing Avian influenza Data database. The thermal shift binding assessment and an enzymatic assay based on fluorescence resonance energy transfer were used to determine the drug sensitivity. The SARS-CoV-2 Mpro mutant proteins were expressed and examined for nirmatrelvir inhibition and enzymatic activity utilizing X-ray crystal structures.
According to the kcat/Km value for enzymatic activity and the Ki value for drug resistance, the Mpro mutants were divided into three categories: category 1 contains essential residues for enzymatic activity ; category 2 contains hot spot residues for drug resistance ; and category 3 comprises residues that can withstand multiple mutations without substantially influencing drug inhibition and the enzymatic activity .
Besides, the X-ray structures illustrated how Mpro mutations influenced the conformational stability of the active site, lowering ligand binding. X-ray structures of six single mutants with or without nirmatrelvir/GC-376 were established.
Australia Latest News, Australia Headlines
Similar News:You can also read news stories similar to this one that we have collected from other news sources.
Study shows long COVID remodeling of T cell dynamics is dependent on SARS-CoV-2 severityA new study found that the post-COVID-19 functional remodeling of T cells occurs in two steps and confers different convalescent immune states, six months after SARS-CoV-2 infection.
Read more »
Scientists report autoimmunity from molecular mimicry between SARS-CoV-2 spike and human proteinsScientists report autoimmunity from molecular mimicry between SARS-CoV-2 spike and human proteins FIU SARSCoV2 COVID19 Coronavirus Spike SpikeProtein HumanProteins
Read more »
Researchers explore disease severity post-infection with SARS-CoV-2 Omicron in hematologic patientsResearchers explore disease severity post-infection with SARS-CoV-2 Omicron in hematologic patients unidue SARSCoV2 COVID19 Coronavirus Omicron Variant HematologicPatients
Read more »
Study finds Omicron variant could break through vaccine protection more effectively than the Delta variantStudy finds Omicron variant could break through vaccine protection more effectively than the Delta variant medrxivpreprint SUNY Omicron vaccine COVID19 coronavirus covid Delta
Read more »
Scientists report autoimmunity from molecular mimicry between SARS-CoV-2 spike and human proteinsScientists report autoimmunity from molecular mimicry between SARS-CoV-2 spike and human proteins FIU SARSCoV2 COVID19 Coronavirus Spike SpikeProtein HumanProteins
Read more »
Researchers explore disease severity post-infection with SARS-CoV-2 Omicron in hematologic patientsResearchers explore disease severity post-infection with SARS-CoV-2 Omicron in hematologic patients unidue SARSCoV2 COVID19 Coronavirus Omicron Variant HematologicPatients
Read more »