Roles of the polybasic furin cleavage site of spike protein in SARS‐CoV‐2 replication, pathogenesis, and host immune responses and vaccination

Hossain, Md. Golzar; Tang, Yan-Dong; Akter, Sharmin; Zheng, Chunfu

doi:10.1002/jmv.27539

Cited by 44 publications

(31 citation statements)

References 51 publications

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“…Moreover, the risk of reinfection of previously COVID‐19 infected patients with the Omicron variant is very evident, indicating higher transmissibility 15 . Omicron variant mutations H655Y and N679K are present near the furin cleavage site (FCS) and can increase spike cleavage, making the virus more contagious 27,28 . On the other hand, P681H can multiply transmissibility by increasing the spike protein cleavage 29 …”

Section: Transmissibility Of Omicron Variantmentioning

confidence: 99%

“…15 Omicron variant mutations H655Y and N679K are present near the furin cleavage site (FCS) and can increase spike cleavage, making the virus more contagious. 27,28 On the other hand, P681H can multiply transmissibility by increasing the spike protein cleavage. 29 Furthermore, the new variant Omicron gives a false negative result in polymerase chain reaction tests because of the "S gene target failure," which paves the way of spreading the infection at a higher speed worldwide.…”

Section: Transmissibility Of Omicron Variantmentioning

confidence: 99%

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Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines

Araf

Akter

Tang

et al. 2022

Journal of Medical Virology

Self Cite

716

544

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Currently, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread worldwide as an Omicron variant. This variant is a heavily mutated virus and designated as a variant of concern by the World Health Organization (WHO). WHO cautioned that the Omicron variant of SARS‐CoV‐2 held a very high risk of infection, reigniting anxieties about the economy's recovery from the 2‐year pandemic. The extensively mutated Omicron variant is likely to spread internationally, posing a high risk of infection surges with serious repercussions in some areas. According to preliminary data, the Omicron variant of SARS‐CoV‐2 has a higher risk of reinfection. On the other hand, whether the current COVID‐19 vaccines could effectively resist the new strain is still under investigation. However, there is very limited information on the current situation of the Omicron variant, such as genomics, transmissibility, efficacy of vaccines, treatment, and management. This review focused on the genomics, transmission, and effectiveness of vaccines against the Omicron variant, which will be helpful for further investigation of a new variant of SARS‐CoV‐2.

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Section: Transmissibility Of Omicron Variantmentioning

confidence: 99%

Section: Transmissibility Of Omicron Variantmentioning

confidence: 99%

Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines

Araf

Akter

Tang

et al. 2022

Journal of Medical Virology

Self Cite

716

544

View full text Add to dashboard Cite

show abstract

“… 5 , 24 S1/S2 cleavage site mutations H655Y, N679K, and P681H result in increased S1/S2 furin cleavage and facilitate efficient viral entry into the host. 25 While, S477N, Q498R, and N501Y mutations affect the ACE‐2 binding affinity, S477N and E484A are responsible for immune evasion. 20 , 26 Further, K317T/N, L452R, Y453F, S477N, E484K, and N501Y mutations were shown to evade neutralization by 11 of the 13 analyzed monoclonal antibodies (mAbs).…”

Section: Mutational Landscape Of Omicron Variantmentioning

confidence: 99%

“Is Omicron mild”? Testing this narrative with the mutational landscape of its three lineages and response to existing vaccines and therapeutic antibodies

Rajpal

Sharma

Kumar

et al. 2022

Journal of Medical Virology

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SARS‐CoV‐2 Omicron with its lineages BA.1, BA.2, and BA.3 has triggered a fresh wave of Covid‐19 infections. Though, Omicron has, so far, produced mild symptoms, its genome contains 60 mutations including 37 in the spike protein and 15 in the receptor‐binding domain. Thirteen sites conserved in previous SARS‐CoV‐2 variants carry mutations in Omicron. Many mutations have shown evolution under positive selection. Omicron's giant mutational leap has raised concerns as there are signs of higher virus infectivity rate, pathogenesis, reinfection, and immune evasion. Preliminary studies have reported waning of immunity after two‐dose primary vaccine regime, need for the boosters, folds reduction in vaccine effectiveness and neutralizing antibodies even after boosting and significant neutralization resistance with the therapeutic monoclonal, polyclonal, and convalescent antibodies against Omicron. The narrative that “Omicron is mild,” therefore, needs time to be tested with a deeper, scientific dwelling into the facts.

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“… 36 However, it was recently demonstrated that additional (booster) mRNA vaccine doses may help to improve anti‐viral antibody responses against new SARS‐CoV‐2 variants. 135 …”

Section: Mutations In Sars‐cov‐2 Variantsmentioning

confidence: 99%

Development of antibody resistance in emerging mutant strains of SARS CoV‐2: Impediment for COVID‐19 vaccines

Beeraka

Sukocheva

Lukina

et al. 2022

Reviews in Medical Virology

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Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a highly infectious agent associated with unprecedented morbidity and mortality. A failure to stop growth of COVID‐19‐linked morbidity rates is caused by SARS‐CoV‐2 mutations and the emergence of new highly virulent SARS‐CoV‐2 strains. Several acquired SARS‐CoV‐2 mutations reflect viral adaptations to host immune defence. Mutations in the virus Spike‐protein were associated with the lowered effectiveness of current preventive therapies, including vaccines. Recent in vitro studies detected diminished neutralisation capacity of vaccine‐induced antibodies, which are targeted to bind Spike receptor‐binding and N‐terminal domains in the emerging strains. Lower than expected inhibitory activity of antibodies was reported against viruses with E484K Spike mutation, including B.1.1.7 (UK), P.1 (Brazil), B.1.351 (South African), and new Omicron variant (B.1.1.529) with E484A mutation. The vaccine effectiveness is yet to be examined against new mutant strains of SARS‐CoV‐2 originating in Europe, Nigeria, Brazil, South Africa, and India. To prevent the loss of anti‐viral protection in vivo, often defined as antibody resistance, it is required to target highly conserved viral sequences (including Spike protein) and enhance the potency of antibody cocktails. In this review, we assess the reported mutation‐acquiring potential of coronaviruses and compare efficacies of current COVID‐19 vaccines against ‘parent’ and ‘mutant’ strains of SARS‐CoV‐2 (Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529)).

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Roles of the polybasic furin cleavage site of spike protein in SARS‐CoV‐2 replication, pathogenesis, and host immune responses and vaccination

Cited by 44 publications

References 51 publications

Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines

Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines

“Is Omicron mild”? Testing this narrative with the mutational landscape of its three lineages and response to existing vaccines and therapeutic antibodies

Development of antibody resistance in emerging mutant strains of SARS CoV‐2: Impediment for COVID‐19 vaccines

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