Cerezo, Miguel Patrick

NS5 Dengue
as a basis of Virulence of DENV to Humans
 Epidemiologic Triad
Interrelations of Various AGENTS, HOST, ENVIRONMENT = STIMULUS

Importance

Corresponds to appropriate intervention between interactions

Characterization of each factor
Ultimately determines epidemiology of the Dengue transmission
Underlying explanation to the rapid evolution of the virus
 Environment Factor

DENGUE Transmission

The magnitude of the dengue problem has

increased dramatically and has extended
geographically to many previously unaffected areas. It
was then, and remains today, the most important
arthropod-borne viral disease of humans. - WHO
 Host Factor

DENGUE Clinical Aspect

 Agent Factor

DENGUE Virulence
 Agent Factor

DENGUE Virulence

Basis of Virulence:

Attachment
Evasion of Detection
Mutation
 Virulence Factor

NS5 Replication Complex

Structure: Function:
aid the development of structure-
4 sets of dimers which are
based inhibitors that would
superimposable to each interfere with inter-domain or
other. (AB, CD, EF, GH) inter-molecular interactions

NS5

Mtase and RdRps: Importance:

RdRps initiate RNA synthesis de
novo, without the need of a function as a dimer in the viral
primer replication complex
Mtase for the SAM-dependent
methyltransferase
 NS5 Importance
Characterization of the protein enables us to understand its virulence

CORE FUNCTION MOST CONSERVED

1 2 3
INTERMOLECULAR
IS FOR VIRAL PROTEIN IN
INTERACTIONS
REPLICATION FLAVIVIRUS

Unique among the DENV

Protective mechanism used in
the need for viral replication of
DENV
Mutation of the proteins
despite very variable to each
involved indicate disruption of
other with regards to other
its replication
structure

ASSOCIATED WITH TARGETED

4 EVASION OF IMMUNE
MECHANISMS 5 PROTEIN FOR
THERAPY

Its essential role in viral

Ability to evade the activity of
replication makes it a desirable
Interferons
target for treatment
 MOA OF NS5
DENGUE VIRUS
ROLE IN VIRAL
REPLICATION Mutation Progression to new strains

IMPLICATION IN
IMMUNITY EVASION
Major target for vaccine Viremia Severity of Symptoms
clinical trials
 Thank You
References:

Yangsheng Zhou ,Debashish Ray, Yiwei Zhao,Hongping Dong,Suping Ren,Zhong Li,

Yi Guo,Kristen A. Bernard, Pei-Yong Shi, andHongmin Li. Structure and Function of
Flavivirus NS5 Methyltransferase. 2013

Andr S. de Oliveira, Milene L. da Silva, Ana Flvia C. S. Oliveira, Cynthia C. da Silva, Rbson R.
Teixeira and Srgio O. De Paula. NS3 and NS5 Proteins: Important Targets for Anti
Dengue Drug Design. 2014.