Immunity evasion: consequence of the N501Y mutation of the SARS-CoV-2 spike glycoprotein

Uzoeto, Henrietta Onyinye; Ajima, Judith Nnedimkpa; Arazu, A. V.; Ibiang, Glory Omini; Cosmas, Samuel; Durojaye, Olanrewaju Ayodeji

doi:10.1186/s43141-021-00287-z

Cited by 9 publications

(7 citation statements)

References 14 publications

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“…By studying the dynamics of emergence of the N 501 Y lineages of SARS-CoV-2 during the COVID-19 pandemic, we found evidence that a cellular receptor-driven selection process can occur during human-to-human transmission of viruses carrying an asparagine at amino acid position 501 (N 501 ) in their spike protein. More precisely, by molecular modeling we demonstrated for the first time, that the encounter of an N 501 virus with a rare allele of ACE2 (E 329 G) could lead to the selection of an N 501 Y lineage SARS-CoV-2 viruses exhibiting higher affinity for the receptor ( 25 ) and lower susceptibility to neutralization by antibodies ( 26 , 27 ).…”

Section: Discussionmentioning

confidence: 97%

Possible contribution of rare alleles of human ACE2 in the emergence of SARS-CoV-2 variants escaping the immune response

Devaux,

Fantini

2023

Front. Immunol.

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Since the start of the SARS-CoV-2 pandemic, the rapid replacement of one lineage by another has been observed. Indeed, SARS-CoV-2 is evolving through a quasispecies mechanism leading to post-infection mutation selection under positive evolutionary pressure (host-driven viral evolution). These mutations may reduce the effectiveness of the specific neutralizing immune response against the virus. We provide here evidence that apart from the selection of SARS-CoV-2 variants by the immune system, selection by the cellular receptor can just as well select variants which escape neutralization.

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Section: Discussionmentioning

confidence: 97%

Possible contribution of rare alleles of human ACE2 in the emergence of SARS-CoV-2 variants escaping the immune response

Devaux,

Fantini

2023

Front. Immunol.

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“…Although several vaccines have received authorization for emergency use, and their deployment is currently ongoing worldwide, vaccinating the entire population of the world will take a long time 6 . New viral escape mutants might also likely emerge as a result of the slow rate of vaccination, eventually making vaccines ineffective 6 , 7 . The development of novel antiviral therapeutics and other broad therapies for possible future emergence is therefore of great necessity.…”

Section: Discussionmentioning

confidence: 99%

“…However, most of these treatment options displayed major setbacks in large clinical trials in hospitalized patients, either exhibiting uncertain efficacy or serious side effects 4 , 5 . Moreover, the SARS-CoV-2 virus mutates frequently, and this is an obstacle to some potential drugs, and the emergence of viral escape mutants that render SARS-CoV-2 spike glycoprotein-targeting vaccines ineffective remains a possibility 6 , 7 . This challenge necessitates the search for broad-spectrum antivirals that will also be effective against possible future variants.…”

Section: Introductionmentioning

confidence: 99%

MasitinibL shows promise as a drug-like analog of masitinib that elicits comparable SARS-Cov-2 3CLpro inhibition with low kinase preference

Durojaye

Okoro

Odiba

et al. 2023

Sci Rep

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SARS-CoV-2 infection has led to several million deaths worldwide and ravaged the economies of many countries. Hence, developing therapeutics against SARS-CoV-2 remains a core priority in the fight against COVID-19. Most of the drugs that have received emergency use authorization for treating SARS-CoV-2 infection exhibit a number of limitations, including side effects and questionable efficacy. This challenge is further compounded by reinfection after vaccination and the high likelihood of mutations, as well as the emergence of viral escape mutants that render SARS-CoV-2 spike glycoprotein-targeting vaccines ineffective. Employing de novo drug synthesis or repurposing to discover broad-spectrum antivirals that target highly conserved pathways within the viral machinery is a focus of current research. In a recent drug repurposing study, masitinib, a clinically safe drug against the human coronavirus OC43 (HCoV-OC43), was identified as an antiviral agent with effective inhibitory activity against the SARS-CoV-2 3CLpro. Masitinib is currently under clinical trial in combination with isoquercetin in hospitalized patients (NCT04622865). Nevertheless, masitinib has kinase-related side effects; hence, the development of masitinib analogs with lower anti–tyrosine kinase activity becomes necessary. In this study, in an attempt to address this limitation, we executed a comprehensive virtual workflow in silico to discover drug-like compounds matching selected pharmacophore features in the SARS-CoV-2 3CLpro-bound state of masitinib. We identified a novel lead compound, “masitinibL”, a drug-like analog of masitinib that demonstrated strong inhibitory properties against the SARS-CoV-2 3CLpro. In addition, masitinibL further displayed low selectivity for tyrosine kinases, which strongly suggests that masitinibL is a highly promising therapeutic that is preferable to masitinib.

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“…However, the sensitivity for most methods is unsatisfactory, despite that they are based on antibodies or aptamers to recognize the antigens. Therefore, it is vital to develop ultrasensitive antigen assay to diagnose SARS-CoV-2 virus infection [23] .…”

Section: Introductionmentioning

confidence: 99%

An ultrasensitive ELISA to assay femtomolar level SARS-CoV-2 antigen based on specific peptide and tyramine signal amplification

Liu

Pang

Wang

et al. 2023

Sensors and Actuators B: Chemical

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Immunity evasion: consequence of the N501Y mutation of the SARS-CoV-2 spike glycoprotein

Cited by 9 publications

References 14 publications

Possible contribution of rare alleles of human ACE2 in the emergence of SARS-CoV-2 variants escaping the immune response

Possible contribution of rare alleles of human ACE2 in the emergence of SARS-CoV-2 variants escaping the immune response

MasitinibL shows promise as a drug-like analog of masitinib that elicits comparable SARS-Cov-2 3CLpro inhibition with low kinase preference

An ultrasensitive ELISA to assay femtomolar level SARS-CoV-2 antigen based on specific peptide and tyramine signal amplification

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