A gapless unambiguous RNA metagenome-assembled genome sequence of a unique SARS-CoV-2 variant encoding spike S813I and ORF1a A859V substitutions

Abstract

The novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is causing an unprecedented pandemic, threatening global health, daily life, and economy. Genomic surveillance continues to be a critical effort towards 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. We here report the successful assembly of one single gapless, unambiguous contiguous sequence representing the complete viral genome from a nasopharyngeal swab of an infected healthcare 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 S-813-I 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. While 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 have not been observed in any of the 197,000 genomes reported to date. Future studies will assess the biological, pathogenic, and epidemiologic implications of this set of genetic variations.

Can molecular mimicry explain the cytokine storm of SARS‐CoV‐2?: An in silico approach

“…This in silico study showed that the SARS‐CoV‐2 Nsp3 protein, is critical for the virus replication in cells, 40 is encoded by ORF1a 41 and/or ORF1ab 42 and has similarity to human PARP14 and PARP9. Thus, PARP14 could be depressed by a phenomenon of molecular mimicry causing the polarization of the M1 macrophage phenotype triggering the SARS‐CoV‐2 related cytokine storm by a hyper‐inflammatory state as well as by the MAS.…”

“…17 On the other hand, PARP9 is an important molecule that provides protection against lethal viral infections through interferon responses, 39 and as PARP14, also participates in the polarization of macrophages towards the M2 phenotype. 17 T A B L E 2 MHC-I and MHC-II alleles prediction epitopes This in silico study showed that the SARS-CoV-2 Nsp3 protein, is critical for the virus replication in cells, 40 is encoded by ORF1a 41 and/or ORF1ab 42 which is responsible for the SARS-CoV-2 related macrophage activation syndrome, however, the presence of this cytokine produces the decrease of NK and CD8 + T cells, 28,47 a condition found in patients with severe SARS-CoV-2 infections. 28,48,49 This scenario produces in the SARS-CoV-2 patient a state of constant hyper-inflammation, without macrophage immune regulation.…”