Sequence, structure and function relationships in flaviviruses as assessed by evolutive aspects of its conserved non-structural protein domains

Abstract

Flaviviruses are responsible for serious diseases such as dengue, yellow fever, and zika fever. Their genomes encode a polyprotein which, after cleavage, results in three structural and seven non-structural proteins. Homologous proteins can be studied by conservation and coevolution analysis as detected in multiple sequence alignments, usually reporting positions which are strictly necessary for the structure and/or function of all members in a protein family or which are involved in a specific sub-class feature requiring the coevolution of residue sets. This study provides a complete conservation and coevolution analysis on all flaviviruses non-structural proteins, with results mapped on all well-annotated available sequences. A literature review on the residues found in the analysis enabled us to compile available information on their roles and distribution among different flaviviruses. Also, we provide the mapping of conserved and coevolved residues for all sequences currently in SwissProt as a supplementary material, so that particularities in different viruses can be easily analyzed.

Cross-serotypically conserved epitope recommendations for a universal T cell-based dengue vaccine

“…Among the top conserved NS5 epitopes, two of them (SRNSTH E MY and LSRNSTH E M) contained an active site (E216) of the enzymatic tetrad of methyltransferase (MTAse) domain known to be critical for viral replication [ 53 ]. Four of the top conserved NS5 epitopes (DTTPFGQQR, TPFGQQRVF, KTWAYHGSY and GPGHEEPIPM) contained residues that are known to be involved in interactions that provide overall stability to the NS5 quaternary structure [ 54 ]. Some residues involved in these epitopes are known to be functionally critical as well [ 53 ]; for example, mutations in epitopes DTTP F GQQR (F349D) and SRNSTH E MY (E216A) were shown to severely impair viral replication.…”

High-throughput fluorescent assay for inhibitor screening of proteases from RNA viruses

“…TBEV protease has not been characterized structurally. However, it is known that the flaviviral NS2B-NS3 pro is a serine protease that is highly conserved among the Flavivirus genus [22]. Therefore, we have chosen to test several commercially available inhibitors that are sufficiently soluble and their interaction with the ZIKV, DENV and WNV proteases was well characterized (DTNB, aprotinin) [17, 18, 29].…”

“…The virology and enzymology of YFV, DEVN, WNV and ZIKV have been studied extensively for the past 30 years, and several kinetic and structural studies of key enzymes are available [16-21]. Significant structural and functional similarity between proteins of a single genus make these findings transferable and instrumental in other studies [22].…”

How Antibodies Recognize Pathogenic Viruses: Structural Correlates of Antibody Neutralization of HIV-1, SARS-CoV-2, and Zika

“…ZIKV is a mosquito-borne virus that can cause microcephaly and neurodevelopmental abnormalities in the newborns of infected mothers [ 34 , 35 , 36 , 37 ]. As part of the flavivirus genus, ZIKV shares similar features as other widespread flaviviruses such as dengue (DENV), West Nile virus (WNV), and yellow fever virus (YFV) [ 38 , 39 , 40 , 41 ]. Mature ZIKV has seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) and three structural proteins: envelope (E), membrane (M), and capsid (C) [ 42 , 43 , 44 ].…”