Sequencing of Slovenian SARS-CoV-2 virus genomes to determine interactions between viral and human proteins

Decembra 2019 je prišlo do izbruha atipične pljučnice na Kitajskem v mestu Vuhan. Analiza genomskega zaporedja je pokazala, da gre za novega predstavnika koronavirusov – virus SARS-CoV-2, sorodnika že znanima povzročiteljema epidemije SARS-CoV in MERS-CoV. Za učinkovito sledenje napredovanja pandemije je ključnega pomena razvoj tehnologije sekvenciranja naslednje generacije. NGS je močno orodje, ki omogoča sprotno ugotavljanje evolucije virusa SARS-CoV-2, ki se dogaja na ravni mutacij genoma. Mutacije se dogajajo spontano pri replikacijskem ciklu virusa in večina se jih ne obdrži v populaciji. Določene mutacije pa se odražajo v povišanem fitnesu virusa in predstavljajo evolucijsko prednost. V raziskavi smo analizirali evolucijo virusa v populaciji Slovenije od 4.3.2020 do 14.6.2021, pri čemur smo uporabili 16.235 virusnih zaporedij, in evolucijo virusa v dveh imunsko oslabljenih osebah. Natančneje smo opisali funkcijo proteina ORF8, ki je potencialna tarča delovanja zdravil. Namesto neposrednega ciljanja virusnega proteina ORF8, bi lahko posredno vplivali na gostiteljeve interaktorje ORF8.In December 2019, an outbreak of atypical pneumonia occurred in Wuhan, China. Genomic sequence analysis has shown that it is a new representative of coronaviruses – SARS-CoV-2, a relative of the already known epidemic-causing SARS-CoV and MERS-CoV. Rapid development of next generation sequencing technology is essential for understanding the ongoing pandemic. NGS is a powerful tool that enables near real-time tracking of SARS-CoV-2 evolution by sequencing its genomic information. Mutations occur spontaneously in the replication cycle of the virus and most of them do not persist in the population. However, certain mutations are reflected in increased fitness of the virus and represent an evolutionary advantage. We analysed the evolution of the virus in the population of Slovenia from March 4, 2020 to June 14, 2021 using 16,235 viral sequences, and the evolution of the virus in two immunocompromised subjects. We described the function of the ORF8 protein, which is a potential target for drug activity. Instead of targeting the ORF8 directly, we propose the option of targeting ORF8 interactors of the host