SARS‐CoV‐2 variants circulating in the Fars province, southern Iran, December 2020–March 2021: A cross‐sectional study

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), the causative virus of the COVID‐19 pandemic, claimed millions of lives worldwide and led to deleterious impacts on health services and the global economy. SARS‐CoV‐2 was first reported in December 2019 in Wuhan, China, and has undergone various mutations similar to many RNA viruses. SARS‐CoV‐2 is a single‐stranded positive‐sense RNA virus with a genome of 29,903 nucleotides and 29 proteins that has six major open‐reading frames (ORFs): ORF1a, ORF1b, S (spike), E (envelope), M (membrane), and N (nucleocapsid), and several accessory ORFs. Numerous significant variants with further infectious and clinical implications have been discovered globally since the onset of the pandemic. Previous studies have shown that the virus takes advantage of mutations in the receptor binding domain (RBD) of the spike, the part of the virus that enters human cells, since this makes it easier for the virus to attach to the human angiotensin‐converting enzyme 2 (ACE2) receptor, resulting in increased viral load and infectivity. Variants were classified into a variant of interest (VOI), a variant of concern (VOC), and a variant of under monitoring (VUM). Some variants have higher transmissibility and severity of the disease and, as a result, increase the mortality and morbidity of the disease. Moreover, created variants can escape the immune system, making the current vaccines ineffective. Nomenclature system methods were developed by GISAID (https://www.gisaid.org/), Nextstrain, and Pango (Phylogenetic Assignment of Named Global Outbreak) to determine the lineage of SARS‐CoV‐2. The World Health Organization Virus Evolution Working Group has suggested using the Greek Alphabet, that is, Alpha, Beta, Gamma, and Delta, for each SARS‐CoV‐2 variant to make public communication much more straightforward. From the onset of the COVID‐19 pandemic until the completion of this study in the middle of March 2021, three variants, including Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1), derived from the Wuhan ancestor. Letters and numbers are used to identify mutations, such as D614G, which indicates that amino acid at position 614 of the spike proteins changed from a D (aspartate) to a G (glycine). Back in March 2020, a significant D614G mutation in the spike glycoprotein of the SARS‐CoV‐2 virus was discovered as a novel variant. This mutation spread to dominate the world, with respective prevalence increased to about 100% by June 2020. In December 2020, Alpha lineage with a vast number of genetic changes, particularly in the spike protein, was detected in the United Kingdom, which continued to expand quickly. Two VOCs, Beta, and Gamma, also appeared in South Africa and Brazil, respectively, after the dramatic rise of the Alpha variant in the United Kingdom. These two VOCs then underwent local transmission throughout the world. All three variants of Alpha, Beta, and Gamma have a mutation at N501Y in which the amino acid asparagine (N) has been replaced by tyrosine (Y) at position 501 in the RBD of the spike protein, making the virus more contagious through facilitating spike protein binding to cellular receptors. In addition, two variants of Beta and Gamma have two additional mutations, K417N/T (substitution of a lysine [K] residue with an asparagine [N] residue or a lysine residue with a threonine) and E484K (substitution of glutamate [E] with lysine [K] at position 484) in the RBD part, which increases the affinity of this part to the ACE2 receptor. From the reported first case of COVID‐19 in Iran on February 19, 2020 until the commencement of this study, there have been several peaks in the SARS‐CoV‐2 infection, primarily due to the introduction of new variants. This study aimed to determine the SARS‐CoV‐2 variants circulating among individuals by performing multiplexed RT‐ qPCR in Fars province, southern Iran.