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Review
. 2022 Apr:148:112756.
doi: 10.1016/j.biopha.2022.112756. Epub 2022 Feb 25.

There is nothing exempt from the peril of mutation - The Omicron spike

Tapan Behl  1 , Ishnoor Kaur  2 , Aayush Sehgal  2 , Sukhbir Singh  2 , Neelam Sharma  2 , Md Khalid Anwer  3 , Hafiz A Makeen  4 , Mohammed Albratty  5 , Hassan A Alhazmi  6 , Saurabh Bhatia  7 , Simona Bungau  8
Affiliations
Review

There is nothing exempt from the peril of mutation - The Omicron spike

Tapan Behl et al. Biomed Pharmacother. 2022 Apr.

Abstract

The 2019 corona virus disease (COVID-19) has caused a global chaos, where a novel Omicron variant has challenged the healthcare system, followed by which it has been referred to as a variant of concern (VOC) by the World Health Organization (WHO), owing to its alarming transmission and infectivity rate. The large number of mutations in the receptor binding domain (RBD) of the spike protein is responsible for strengthening of the spike-angiotensin-converting enzyme 2 (ACE2) interaction, thereby explaining the elevated threat. This is supplemented by enhanced resistance of the variant towards pre-existing antibodies approved for the COVID-19 therapy. The manuscript brings into light failure of existing therapies to provide the desired effect, however simultaneously discussing the novel possibilities on the verge of establishing suitable treatment portfolio. The authors entail the risks associated with omicron resistance against antibodies and vaccine ineffectiveness on one side, and novel approaches and targets - kinase inhibitors, viral protease inhibitors, phytoconstituents, entry pathways - on the other. The manuscript aims to provide a holistic picture about the Omicron variant, by providing comprehensive discussions related to multiple aspects of the mutated spike variant, which might aid the global researchers and healthcare experts in finding an optimised solution to this pandemic.

Keywords: ACE2; Corona virus; Omicron; Receptor binding domain; Spike; Variant of concern.

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Conflict of interest statement

There is no conflict of interest in the submission of the manuscript.

Figures

ga1
Graphical abstract
Fig. 1
Fig. 1
Features of Omicron variant highlighting the structure and subunits; rigid plasma membrane binding via ACE2 and TMPRSS2; limited therapeutic options with reduced number of effective antibodies and antibody evasion from vaccinated sera. [ACE2 – angiotensin converting enzyme-2; TD - tetramerization domain; NTD – N-terminal domain; TMPRSS2 - Transmembrane serine protease 2].
Fig. 2
Fig. 2
Entry pathways of omicron – Plasma membrane (ACE2 and TMPRSS2) and endosomal (cathepsin), inhibited by respective blockers – camostat (TMPRSSE2 blockage) and E64-D (cathepsin blockage).
See this image and copyright information in PMC

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