Invest Clin 63(3): 262 - 274, 2022 https://doi.org/10.54817/IC.v63n3a05

Corresponding author: Flor H Pujol. Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celu-

lar, Instituto Venezolano de Investigaciones Científicas, Caracas, Miranda, Venezuela. E-mail: fhpujol@gmail.com

Sub-lineages of the Omicron variant

of SARS-CoV-2: characteristic mutations

and their relation to epidemiological

behavior.

José Luis Zambrano1, Rossana C Jaspe2, Mariana Hidalgo3, Carmen L Loureiro2,

Yoneira Sulbarán2, Zoila C Moros1, Domingo J Garzaro2, Esmeralda Vizzi4,

Héctor R Rangel2, Ferdinando Liprandi4, and Flor H Pujol2

1Laboratorio de Virología Celular, Centro de Microbiología y Biología Celular,

Instituto Venezolano de Investigaciones Científicas, Caracas, Miranda, Venezuela.

2Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular,

Instituto Venezolano de Investigaciones Científicas, Caracas, Miranda, Venezuela.

3Laboratorio de Inmunoparasitología, Centro de Microbiología y Biología Celular,

Instituto Venezolano de Investigaciones Científicas, Caracas, Miranda, Venezuela.

4Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular,

Instituto Venezolano de Investigaciones Científicas, Caracas, Miranda, Venezuela.

Key words: COVID-19; SARS-CoV-2; Omicron Variant of Concern; mutations; tropism.

Abstract. By the end of 2021, the Omicron variant of SARS-CoV-2, the

coronavirus responsible for COVID-19, emerges, causing immediate concern,

due to the explosive increase in cases in South Africa and a large number of

mutations. This study describes the characteristic mutations of the Omicron

variant in the Spike protein, and the behavior of the successive epidemic waves

associated to the sub-lineages throughout the world. The mutations in the

Spike protein described are related to the virus ability to evade the protec-

tion elicited by current vaccines, as well as with possible reduced susceptibil-

ity to host proteases for priming of the fusion process, and how this might be

related to changes in tropism, a replication enhanced in nasal epithelial cells,

and reduced in pulmonary tissue; traits probably associated with the apparent

reduced severity of Omicron compared to other variants.

Omicron variant 263

Vol. 63(3): 262 - 274, 2022

Sub-linajes de la variante Ómicron del SARS-CoV-2: mutaciones

características y su relación con el comportamiento

epidemiológico.

Invest Clin 2022; 63 (3): 262 – 274

Palabras clave: COVID-19; SARS-CoV-2; variante de preocupación Ómicron;

mutaciones; tropismo.

Resumen. A finales de 2021 surge la variante Omicron del SARS-CoV-2, el

coronavirus responsable de la COVID-19, causando preocupación inmediata,

debido al aumento explosivo de casos en Suráfrica, y a su gran cantidad de

mutaciones. Este estudio describe las mutaciones características de la variante

Ómicron en la proteína de la Espiga (S) y el comportamiento de las sucesivas

olas epidémicas asociadas a la circulación de sus sub-linajes en todo el mundo.

Las mutaciones en la proteína S descritas están relacionadas con su capacidad

para evadir la protección provocada por las vacunas actuales, así como su posi-

ble susceptibilidad reducida a las proteasas del hospedero para la preparación

del proceso de fusión. Se infiere cómo esto podría estar relacionado con su

cambio en el tropismo, con una replicación mayor en las células epiteliales

nasales y menor en el tejido pulmonar, rasgos probablemente asociados a su

aparente menor gravedad en comparación con otras variantes.

Received: 10-07-2022 Accepted: 22-07-2022

INTRODUCTION

SARS-CoV-2 infection, responsible for

the COVID-19 pandemic, has caused more

than 550 million cases and more than 6

million deaths worldwide until June 2022.

This virus belongs to the family Coronaviri-

dae. This family comprises enveloped virus-

es, with a positive sense genome of around

30,000 nt. In the case of SARS-CoV-2, the

genome codes for four structural proteins

(nucleocapsid or N, spike or S, membrane

or M and envelope or E), 15 non-structural

proteins and eight accessory proteins. The S

protein contains two regions: S1, which in-

cludes the receptor-binding domain (RBD),

and S2, with the furin-cleavage site and the

fusion peptide. RBD, specifically the receptor

binding motif (RBM), is the region respon-

sible for the attachment to the angiotensin-

converting enzyme 2 (ACE2) cellular recep-

tor (Fig. 1)1,2. Two other putative receptors

(Asialoglycoprotein Receptor 1 - ASGR1- and

KREMEN1) have been described recently for

SARS-CoV-2, which are not used by the previ-

ous SARS-CoV. The virus appears to interact

with these two additional receptors through

the RBD and also with N-terminal domain of

the S1 region3,4. These new candidates add

to the list of other potential ligands that

may interact with SARS-CoV-25,6.

During these two years of a high rate

of replication, this virus has accumulated

several mutations, allowing for its clas-

sification in more than 2000 lineages by

June 20227-9. Some of these lineages were

denominated as variants by WHO10. These

variants (lineages of viruses sharing partic-

ular types of mutations) emerged since the

end of 2020, and were defined as Variants

Under Monitoring (VUM), Variants of Inter-

est (VOI), and Variants of Concern (VOC),

264 Zambrano et al.

Investigación Clínica 63(3): 2022

when any different phenotypic trait, such as

increased transmissibility or immune eva-

sion, among others, was suspected for the

two firsts and confirmed for the last10. Until

June 2022, five VOCs were described: Al-

pha variant, which emerged in the UK (lin-

eage B.1.1.7), Beta variant in South Africa

(B.1.351), Gamma variant in Brazil (P1),

Delta variant in India (B.1.617.2), and Omi-

cron variant, first identified in South Africa

(B.1.1529). The last one was included in

the list of VOCs very soon after its identi-

fication. By the end of June, only the Omi-

cron VOC and its sub-lineages were present

as a VOC10.

This variant caused immediate concern,

due to the explosive increase in cases in

South Africa11, and the large number of mu-

tations exhibited by this new lineage. In this

study, we describe the characteristic muta-

tions of the Omicron variant of SARS-CoV-2,

and the behavior of the epidemic waves as-

sociated with the dissemination of the differ-

ent sub-lineages throughout the world.

MATERIALS AND METHODS

Description of the mutations charac-

teristic of each sub-lineage of Omicron.

The identification of characteristic muta-

Fig. 1. Mutations of the SARS-CoV-2 Omicron VOC sub-lineages. Venn diagram showing common mutations

between the SARS-CoV-2 Omicron VOC sub-lineages.