A Gapless, Unambiguous RNA Metagenome-Assembled Genome Sequence of a Unique SARS-CoV-2 Variant Encoding Spike S813I and ORF1a A859V Substitutions.

The novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is causing an unprecedented pandemic, threatening planetary health, society, and economy. Genomic surveillance continues to be a critical effort toward tracking the virus and containing its spread, and more genomes from diverse geographical areas and different time points are needed to provide an appropriate representation of the virus evolution. In this study, we report the successful assembly of one single gapless, unambiguous contiguous sequence representing the complete viral genome from a nasopharyngeal swab of an infected health care worker in Cairo, Egypt. The sequence has all typical features of SARS-CoV-2 genomes, with no protein-disrupting mutations. However, three mutations are worth highlighting and future tracking: a synonymous mutation causing a rare spike S813I variation and two less frequent ones leading to an A41V variation in NSP3, encoded by ORF1a (ORF1a A895V), and a Q677H variation in the spike protein. Both affected proteins, S and NSP3, are relevant to vaccine and drug development. Although the genome, named CU_S3, belongs to the prevalent global genotype, marked by the D614G spike variation, the combined variations in the spike proteins and ORF1a do not co-occur in any of the 197,000 genomes reported to date. Future studies will assess the biological, pathogenic, and epidemiological implications of this set of genetic variations. This line of research is needed to inform vaccine and therapeutic innovation to stem the COVID-19 pandemic.