Thread by @SystemsVirology

Please notice: we revealed that SARS-CoV-2 ORF3b, one of the most different genes compared to SARS-CoV, strongly hampers human type I IFN activation. Its inhibitory activity is stronger than the SARS-CoV ortholog and influenza A virus NS1. #COVID19 1/7
biorxiv.org/content/10.110…

Our findings may explain the poor IFN responses in #COVID19 patients and SARS-CoV-2-infected cells compared to SARS-CoV- and influenza A virus-infected cells, recently reported by @DBM003 @virusninja and so on, are attributed to the remarkable ability of SARS-CoV-2 ORF3b. 2/7

Additionally, we revealed that the ORF3b genes of SARS-CoV-2-related viruses in bats and pangolins are very similar to that of SARS-CoV-2 and possess the activity to inhibit IFN activation. 3/7

Interestingly, although “authentic” SARS-CoV-2 ORF3b is much shorter than the SARS-CoV ortholog, we found a “hidden” SARS-CoV ORF3b-like sequence in the SARS-CoV-2 genome. This means that SARS-CoV-2 ORF3b is shortened due to the insertion of premature stop codons. 4/7

Moreover, by using #GLUE, a webtool provided by @CVRinfo, we screened ORF3b derivatives in @GISAID dataset. Strikingly, we detected at least 2 SARS-CoV-2 sequences, reported from Ecuador🇪🇨, that encode an extended ORF3b gene by the loss of stop codon. 5/7

Finally, we experimentally demonstrated that the extended ORF3b exhibits stronger activity to impair IFN activation.
And an important information from a doctor in Ecuador🇪🇨 - both 2 patients infected with these variants exhibited severe #COVID19 disorders and one died. 6/7

Altogether, our findings suggest that the emergence of SARS-CoV-2 quasispecies encoding extended ORF3b during current pandemic may exacerbate #COVID19 symptoms.

That’s all! Thanks for reading this thread🦇 7/7