Variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Vaccine Effectiveness

Abstract

The incidence and death toll due to SARS-CoV-2 infection varied time-to-time; and depended on several factors, including severity (viral load), immune status, age, gender, vaccination status, and presence of comorbidities. The RNA genome of SARS-CoV-2 has mutated and produced several variants, which were classified by the SARS-CoV-2 Interagency Group (SIG) into four major categories. The first category; “Variant Being Monitored (VBM)”, consists of Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Epsilon (B.1.427, B.1.429), Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Mu (B.1.621), and Zeta (P.2); the second category; “Variants of Concern” consists of Omicron (B.1.1.529). The third and fourth categories include “Variants of Interest (VOI)”, and “Variants of High Consequence (VOHC)”, respectively, and contain no variants classified currently under these categories. The surge in VBM and VOC poses a significant threat to public health globally as they exhibit altered virulence, transmissibility, diagnostic or therapeutic escape, and the ability to evade the host immune response. Studies have shown that certain mutations increase the infectivity and pathogenicity of the virus as demonstrated in the case of SARS-CoV-2, the Omicron variant. It is reported that the Omicron variant has >60 mutations with at least 30 mutations in the Spike protein (“S” protein) and 15 mutations in the receptor-binding domain (RBD), resulting in rapid attachment to target cells and immune evasion. The spread of VBM and VOCs has affected the actual protective efficacy of the first-generation vaccines (ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BNT162b2). Currently, the data on the effectiveness of existing vaccines against newer variants of SARS-CoV-2 are very scanty; hence additional studies are immediately warranted. To this end, recent studies have initiated investigations to elucidate the structural features of crucial proteins of SARS-CoV-2 variants and their involvement in pathogenesis. In addition, intense research is in progress to develop better preventive and therapeutic strategies to halt the spread of COVID-19 caused by variants. This review summarizes the structure and life cycle of SARS-CoV-2, provides background information on several variants of SARS-CoV-2 and mutations associated with these variants, and reviews recent studies on the safety and efficacy of major vaccines/vaccine candidates approved against SARS-CoV-2, and its variants.

Keywords: COVID-19; Omicron; SARS-CoV-2; Variants Being Monitored; Variants of Concern; Variants of High Consequence; delta; vaccine efficacy; variants of interest.

Figure 1

Genomic Organization and Structural Features of surface glycoprotein of SARS-CoV-2: (A) Structure of SARS-CoV-2: The schematic depicts the structural features of SARS-CoV-2 virus particle, which contains a single-stranded RNA, S-glycoprotein, and other structural proteins that include envelope (E), membrane (M), and nucleocapsid (N) proteins. (B) Schematic representation of SARS-CoV-2. proteins: Genome of SARS-CoV-2 consists of approximately 29,903 nucleotides, with ORF-1a and ORF-1b, which are translated to polyprotein 1a (pp1a) and 1ab (pp1ab), respectively. Four genes encoding for structural proteins such as spike (S), envelop (E), membrane (M), and nucleocapsid (N). Accessory proteins (ORF3a, 6, 7a, 7b, 8, and 10) are distributed among structural proteins. (C) Structure of SARS-CoV-2 Surface glycoprotein (S): The surface glycoprotein (S protein) is made up of 1273 amino acids, including N-terminal signal peptide (SP), S1 subunit, and S2 subunit. The S1 subunit contains an N-terminal domain (NTD) and a receptor binding domain (RBD), while the S2 subunit is composed of the fusion peptide (FP), heptapeptide repeat sequence 1 (HR1), HR2, TM domain, and cytoplasm domain (C).

Figure 2

Complete life cycle of SARS-CoV-2. SARS-CoV-2 lifecycle begins with primary binding of the Spike protein to its specific receptors (ACE2). Mostly host cell entry depends on several steps: (i) Initial cleavage of S1/S2 specific sites by surface transmembrane protease serine-2 (TMPRSS2) and furine, (ii) followed by virus–cell membrane fusion and endocytosis. (iii) Continuing from endocytosis, m-RNA genome is mainly released into the cytosol and translated into the polyproteins. Mostly polyproteins (pp1a and pp1ab) are cleaved by specific viral-encoded protease (VEP) into the several nonstructural proteins (nsps) (mostly including RNA-dependent RNA polymerase: RdRp) which is responsible for replication transcription complex (RTC) in the cells. (iv) Viral replication begins with virus-induced double membrane vesicles mainly derived from the endoplasmic reticulum (ER). (v) Positive-strand of genome serves as a main template for full-length negative-strand RNA and sub genomic (sg)RNA and sgRNA translation results in both structural proteins and accessory proteins are inserted into the ER–Golgi intermediate compartment (ERGIC) for virion assembly, respectively. (vi) RNA genomes with specific nucleocapsid proteins are incorporated into newly synthesized virions, which are secreted by exocytosis. DMV—double-membrane vesicle.

Figure 3

Mutations reported in amino acid positions of spike glycoproteins (S) in current circulating variant of concern (VOC): Omicron (5.1.1.529) and some Variants Being Monitored: Delta (B.1.617.2), Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1).