Structure and function of capsid protein in flavivirus infection and its applications in the development of vaccines and therapeutics

Abstract

Flaviviruses are enveloped single positive-stranded RNA viruses. The capsid (C), a structural protein of flavivirus, is dimeric and alpha-helical, with several special structural and functional features. The functions of the C protein go far beyond a structural role in virions. It is not only responsible for encapsidation to protect the viral RNA but also able to interact with various host proteins to promote virus proliferation. Therefore, the C protein plays an important role in infected host cells and the viral life cycle. Flaviviruses have been shown to affect the health of humans and animals. Thus, there is an urgent need to effectively control flavivirus infections. The structure of the flavivirus virion has been determined, but there is relatively little information about the function of the C protein. Hence, a greater understanding of the role of the C protein in viral infections will help to discover novel antiviral strategies and provide a promising starting point for the further development of flavivirus vaccines or therapeutics.

Plant-Derived Recombinant Vaccines against Zoonotic Viruses

“…Similar to all other Flaviviruses, DENV's genome is made up of a positive-sense single strand RNA, which has a single ORF encoding all structural and non-structural proteins into one polyprotein. The polyprotein is then proteolytically cleaved into three structural proteins (capsid, precursor membrane, and envelope) and at least seven non-structural (NS) proteins [209]. DENV has four antigenically distinct serotypes (DENV-1-4) [210].…”

Antiviral Agents against Flavivirus Protease: Prospect and Future Direction

“…The Flavivirus genome consists of a positive-sense single-stranded RNA which is ∼11 kb in length, consisting of a single long open reading frame (ORF) flanked by a 5′ untranslated region (UTR) and a 3′ UTR [ 3 , 4 , 19 , 20 ]. The viral genome is not polyadenylated but capped as in cellular mRNA.…”

“…The flavivirus protease is highly conserved and essential for virus replication. The viral PP is processed to three structural proteins (Capsid, pr-Membrane, and Envelope) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [ 4 , 20 ]. Three structural proteins form the virus shell, whereas seven NS proteins participate in the membrane-bound replication complex.…”

Antiviral Agents Against Flavivirus Protease: Prospect and Future Direction

“…Flavivirus genome consists of a positive-sense single-stranded RNA which is ∼11 kb in length, consisting of a 5′ untranslated region (UTR), a single long open reading frame (ORF), and a 3′ UTR [3,4,20,21]. It is capped like cellular mRNAs, but not polyadenylated.…”

“…The flavivirus protease, which works with host proteases to cleave the viral PP, is a highly conserved enzyme essential for virus replication. The viral PP is processed to three structural proteins (Capsid, pr-Membrane, and Envelope) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [4,21]. Three structural proteins form the virus coat, whereas seven NS proteins are part of the membrane-bound replication complex.…”