The Use of Alphavirus Protease for Inhibition of Virus Replication
Date
2021
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Abstract
Alphaviruses are positive-strand RNA viruses, 12 kb in length, belonging to Togaviridae
family. They are transmitted through arthropod vectors, can infect humans, and
cause various of diseases. Structurally, they consist of two ORFs, one of which encodes
four non-structural proteins that serve as viral replication machinery. Another ORF encodes
three structural proteins. Studying the process of correct proteolytic processing of
non-structural polyprotein which leads to production of nsPs is crucial for alphavirus replication
life cycle. Alphaviral nsP2 protease has diverse functions including regulation of
cleavages within the polyprotein and inhibition of cellular activities. The main aim of the
thesis was the investigation of the inhibitory effect of six different versions of singleresidue
substitutions in SINV nsP2 protease to SINV-specific template/replicase RNAs as
well as the inhibitory level of SINV nsP2 proteases on replication of different Alphaviruses.
According to the results the SINV nsP2 N614D mutant was the strongest inhibitor
among other six versions of SINV nspP2 tested, but the inhibition level of other mutants of
SINV nsP2 on other Alphaviruses replication was not prominent. Neither vaccine nor antiviral
therapy against Alphaviruses is available up to date, together with its frequent incidence
of outbreaks have emphasized the necessity to study Alphaviruses. Current study
can give an insight into the most important aspects of its replication and give a possibility
to use this knowledge in order to elaborate different approaches for antiviral therapy.
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Keywords
Alphavirus, nsP2, inhibition, protease, Sindbis virus