Systematic analysis of RNAi-accessible SARS-CoV-2 replication steps identifies ORF1 as promising target

A promising approach to combat SARS-CoV-2 constitute small interfering (si)RNAs. We systematically analyzed which SARS-CoV-2 replication steps are accessible for RNAi. We found that siRNAs can target the genome of incoming SARS-CoV-2 terminating replication after cell entry and preventing cytopathy. Suprisingly, siRNAs were not active against intermediate negative sense transcripts. Targeting sequences shared by different viral transcripts allowed simultaneous suppression of genomic and subgenomic viral RNAs by a single siRNA. The most effective suppression of viral replication and spread was achieved by siRNAs targeting open reading frame 1 (ORF1) which is solely part of genomic RNA. We propose that an improved accessibility of translational-active ORF1 during early replication, as well as the outcompetition of RNAi factors by common sequences of transcripts are responsible for this. Our work encourages efforts to develop siRNA-based therapies for COVID-19. Targeting ORF1, together with early treatment start or prophylactic use may be key for high antiviral efficiency.

Genome Sequences of Novel Torque Teno Viruses Identified in Human Brain Tissue

ABSTRACT Complete genome sequences of two novel torque teno viruses (TTVs) were identified in human brain tissue. These sequences are 3,245 nucleotides (nt) and 2,900 nt long and share 68% and 72% open reading frame 1 (ORF1) identity, respectively, with other human TTVs. This report extends the identification of TTV sequences in the brain.

Partial Genome Sequences of Human Norovirus Strains from Northeast Brazil

Noroviruses are the leading cause of human gastroenteritis worldwide. Here, we sequenced the open reading frame 1 (ORF1)-ORF2 junction region of norovirus strains isolated from 20 human stool samples. Samples were collected between 2014 and 2017 in Pernambuco State, Brazil. Phylogenetic analyses identified four norovirus GII genotypes circulating in this area of the country.

Complete Genome Sequence of Beak and Feather Disease Virus Isolated from an African Grey Parrot in China in 2017

ABSTRACT The complete nucleotide (nt) sequence of beak and feather disease virus (BFDV) was determined. The viral genome consists of 1,991 nt, including an 870-nt open reading frame 1 (ORF1), a 744-nt ORF2, a conserved stem-loop structure, and the second hairpin. This is the first reported detection of BFDV in an infected African grey parrot in China.

A CASE OF IMPORT OF GENOTYPE 4 HEPATITIS E VIRUS INTO RUSSIA

Aim. Description of the first documented case of imported hepatitis E, associated with genotype 4 of HEV and introduced from southern France. Materials and methods. Clinical, epidemiologic and laboratory analysis of the imported case of disease of hepatitis E was carried out. Phylogenetic analysis of nucleotide sequences of HEV isolate, taken from the patient, was carried out. Results. Epidemiologic analysis allowed to assume imported character of the detected case of HEV-infection. Comparative analysis of nucleotide sequences of regions of the open reading frame 2 (300 nt) and open reading frame 1 (721 nt) of HEV genome, isolated from the patient, showed identity of this isolate with variants of genotype 4 HEV, isolated in France in 2009 - 2011 from patients with autochthonous hepatitis E. Conclusion. The results obtained confirm the case of import into Russia of genotype 4 HEV from south-eastern France (Corsica), where spread of this virus genotype is observed in recent years.