Maison, D. P. | bioRxiv Science

bioRxiv2021

Algorithm for the Quantitation of Variants of Concern for Rationally Designed Vaccines Based on the Isolation of SARS-CoV-2 Hawaii Lineage B.1.243

SARS-CoV-2 worldwide emergence and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired clinical samples, analyzed SARS-CoV-2 genomes, used the most worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the SARS-CoV-2 vaccine platform. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearsons correlation determines exponential emergence. The SARS-CoV-2 genome evaluation indicated 49 mutations. Nine of the ten most worldwide prevalent (>70%) spike protein changes have r-values >0.9. The tenth, D614G, has a prevalence >99% and r-value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. SARS-CoV-2 is predicted to remain endemic and continues to evolve, so must SARS-CoV-2 monitoring and next-generation vaccine design.

molecular biology↗

bioRxiv2021

Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawaii Reveals the Worldwide Emerging P681H Mutation

COVID-19 pandemic has ravaged the world, caused over 1.8 million deaths in the first year, and severely affected the global economy. Hawaii is not spared from the transmission of SARS-CoV-2 in the local population, including high infection rates in racial and ethnic minorities. Early in the pandemic, we described in this journal various technologies used for the detection of SARS-CoV-2. Herein we characterize a 969-bp SARS-CoV-2 segment of the S gene downstream of the receptor-binding domain. At the John A. Burns School of Medicine Biocontainment Facility, RNA was extracted from an oropharyngeal swab and a nasal swab from two patients from Hawaii who were infected with the SARS-CoV-2 in August 2020. Following PCR, the two viral strains were sequenced using Sanger sequencing, and phylogenetic trees were generated using MEGAX. Phylogenetic tree results indicate that the virus has been introduced to Hawaii from multiple sources. Further, we decoded 13 single nucleotide polymorphisms across 13 unique SARS-CoV-2 genomes within this region of the S gene, with one non-synonymous mutation (P681H) found in the two Hawaii strains. The P681H mutation has unique and emerging characteristics with a significant exponential increase in worldwide frequency when compared to the plateauing of the now universal D614G mutation. The P681H mutation is also characteristic of the new SARS-CoV-2 variants from the United Kingdom and Nigeria. Additionally, several mutations resulting in cysteine residues were detected, potentially resulting in disruption of the disulfide bridges in and around the receptor-binding domain. Targeted sequence characterization is warranted to determine the origin of multiple introductions of SARS-CoV-2 circulating in Hawaii.

evolutionary biology↗