Genomic analysis of SARS-CoV-2 variants: diagnosis and vaccination challenges

Abstract

SARS-CoV-2 put a heavy financial burden on the healthcare system, with millions of laboratory-confirmed cases and deaths worldwide in the last 2 years. During the seventh wave of this pandemic, the continuously evolving nature of SARS-CoV-2 resulted in the emergence of new variants that harbor different mutations. Mutations are associated with changes in the virus behavior, including increased transmissibility, increased virulence, and evasion of neutralizing antibodies. Currently, we need detailed and comprehensive genomic information on all SARS-CoV-2 variants. One of the key points in this study was the genome survey of mutation profiles across variants as a genomic data source, to determine the efficiency of RT-qPCR assays. We also used the source to calculate the binding affinity changes of neutralizing antibodies–mutant receptor binding domain (RBD) complexes and determine vaccine efficacy. Our result revealed that the number of nucleotide mismatches is variable in the WHO-recommended primer-probe sets. Mismatches located at the 3′ ends of the oligonucleotide, may lead to false-negative results. Only the primer-probe sets designed by the Ministry of Public Health of Thailand were exclusive and cannot detect the omicron variant reliably. Binding affinity changes showed that E484K was more deleterious than other mutations and decreased stability between the mutant RBD protein and neutralizing antibodies. The Omicrons show the highest change in binding affinity which may lead to immune escape and increase transmissibility. Additionally, the 7D6 monoclonal antibody in the 7eam complex could neutralize all variants of SARS-CoV-2. We strongly recommend creating and improving a matrix accuracy by processing a large number of SARS-CoV-2 sequences to update RT-qPCR assays and identified immunogenic residues among conserved RBD. Also, a detail computational analysis is needed to investigate distinctive amino acid substitution patterns which may be foundational in the vaccines. Finally, designing in-vitro studies can help confirm the present study and manage COVID-19 patients. Communicated by Ramaswamy H. Sarma