Descriptive Analysis of Ebola virus Proteins: Towards Development of Effective Therapeutics and Vaccines

Abstract

Ebola virus (EBOV) is a non-segmented enveloped RNA virus. It has seven structural proteins and three non-structural proteins (∆-peptide, ssGP and sGP). Structural proteins include viral proteins (VP24, VP30, VP35, and VP40), glycoprotein(GP), nucleoprotein(NP) and RNA polymerase L. The functions of structural proteins range from replication, transcription and maintenance of the structural stability of EBOV. VP24 and VP35 are well known for suppressing host interferon (IFN) response systems. There are no approved treatments for Ebola virus disease (EVD). However, several virus vectored vaccines aimed at inducing B and T cell immunity against GP and NP are currently under development or undergoing clinical trials. Unlike virus vectored vaccines, virus like particle (VLP) based vaccines have been developed to elicit immunity against GP, NP, and VP40. They can also be engineered to include VP24 and VP35. Several compounds such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), c3-NpcA, peptides, NSC629, E64, compound 3.47, compound 7, CA074, and Ca-c3 Ado that target different stages of the EBOV replication cycle have been found to be effective. Other compounds such as recombinant nematode anticoagulant protein c2 (rNAPc2) and Recombinant human activated protein C (rhAPC) have been designed to reduce coagulopathies seen in late stages of EVD. Cocktails of neutralising monoclonal antibodies are also effective against EBOV alone or in combination with IFNs. Therefore, this review discusses the structure and mechanism of action of EBOV proteins, current promising therapeutics and vaccines against EBOV, and different ways of improving their efficacy.